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Video stored in live bacterial genome using CRISPR gene …

Photos from Eadweard Muybridges study of a galloping horse have been recorded in bacterial DNA

Eadweard Muybridge/The LIFE Picture Collection/Gett

By Douglas Heaven

Life is an open book and were writing in it. A team at Harvard University has used the CRISPR genome-editing tool to encode video into live bacteria demonstrating for the first time that we can turn microbes into librarians that can pass records on to their descendants and perhaps to ours.

The technique could even let us create populations of cells that keep their own event logs, making records as biological processes like disease or brain development happen.

DNA is one of the best media for storing data we know of. Researchers have already crammed large amounts of information from books to digital images into tiny amounts of biological material. In theory, a gram of single-stranded DNA can encode 455 exabytes, or roughly 100 billion DVDs.


Most previous DNA storage work has used artificial DNA: digital information is translated into a DNA sequence that is then synthesized.

However, using CRISPR lets you cut and paste the digital information directly into the DNA of a live organism, in this case a large population of E. coli.

Bacteria use the CRISPR/Cas9 system to record information in their DNA about viruses they encounter. And this machinery has been co-opted by researchers to enable us to precisely edit genomes.

In bacteria, each new entry gets stored upstream of the last one, which makes it possible to read off a history of events in the order they happened. Previous groups have created lifelogging cells by using CRISPR/Cas9 to mark the genome when a particular event occurs. But these marks just provide a tally of how many times something happens.

Seth Shipman at Harvard University and his colleagues have now used a version of CRISPR with a different enzyme, called CRISPR/Cas1-Cas2. This let them add a message to the genome rather than simply cut a notch.

The message was a recorded image of a human hand and five images showing a galloping horse, taken from Eadweard Muybridges 1878 photographic study of the animals motion, which has since been animated.

Seth Shipman

To get the DNA sequences encoding this data inside the cells, the team applied an electrical current that opened channels in the cells walls and the DNA flowed in. Once inside, CRISPR got to work.

To read the data back again, the team sequenced the DNA of more than 600,000 cells. The large number is necessary because most cells will not have edited their genome entirely accurately. Every cell isnt going to acquire every piece of information we throw at it, says Shipman. The more cells that are sampled, the better the reconstruction of the data. Fortunately, with modern sequencing tools, reconstruction is quick.

The five frames of a horse in motion showed that it is possible to capture data chronologically and replay them as a video. You get a physical record of events over time, says Shipman. For a long time we wanted to have some way of storing timing information inside cells, says Shipman. The CRISPR system is perfectly adapted to that.

This is a really neat paper, says Yaniv Erlich at Columbia University in New York. The team didnt store that much data and it is not clear that the CRISPR technique can compete with the storage capacity of synthetic DNA. But inserting information into living cells opens up a lot of possibilities, he says.

For a start, it lets you add to or change the stored information later. And because the data is written into the bacterial genomes, it gets passed down between generations. Mutations happen, but not nearly as many as you think, says Shipman certainly not enough to corrupt the data stored across a large population of cells.

Storing data in bacteria could even be a way to make important information survive a nuclear apocalypse. You could useDeinococcus radiodurans, a species that maintains its genome in extreme radiation conditions, says Erlich.

Shipman wants to turn cells into recording devices that document what takes place inside themselves. He is excited about the possibility of keeping a log book of events inside a living brain as it develops, showing how different brain cells acquire their distinct identities.

Its hard to understand what events make brain cells fully defined, says Shipman. You cant easily get in there to take a look. Taking a brain apart disrupts the whole process.

You could also get a cell to diarise what happens as it changes from healthy to diseased. Now that would be an account worth reading.

Journal reference: Nature, DOI: 10.1038/nature23017

More on these topics:

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Bone Marrow and Stem Cell Transplant Program UNM …

The Bone Marrow and Stem Cell Transplant Center at the UNM Comprehensive Cancer Center offers treatment choices for people with lymphoma and myeloma.Almost 1,000 New Mexicans receive a blood cancer diagnosis each year, according to American Cancer Society estimates.

The UNM Comprehensive Cancer Center program is the states only bone marrow transplant program.It includes a nurse manager, nurse coordinator, a social worker, a pharmacist, infusion nurses, and an inpatient team. Bone marrow transplantation needs a multidisciplinary team because of the complexity in coordinating care, says Fero. The teams Nurse Manager, Maria Limanovich, says the team follows each person from the beginning of bone marrow transplant treatment through completion.

Bone marrow, the soft reddish material that fills the inside of our bones, produces millions of new blood cells each second. These millions of cells come from a tiny number of bone marrow stem cells. These stem cells are special because they can mature into all of the different types of cells in the blood. These are the cells doctors collect for a transplant.

Autologous bone marrow transplants are standard treatments for lymphoma and myeloma.

Matthew Fero, MD, FACPBone Marrow Stem Cell Program Director

Because bone marrow is a liquid organ, Fero says, it can pass through an IV [intravenous] line. Doctors rarely need to take stem cells directly out of the bone, Fero explains. They use drugs to coax bone marrow stem cells into the bloodstream. From there, the blood travels through an IV line into an apheresis machine that sorts the stem cells out and returns the rest of the blood. The experience is like donating blood at a blood bank.

Once stem cells are safely stored out of the bloodstream, doctors use high-dose chemotherapy to eradicate the remaining cancer. When chemotherapy is out of their system, the patients stem cells are reinfused. The process is similar to blood transfusion. Stem cells find their way back to bone marrow where they begin to grow and make new blood cells.

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Hypogonadism Testosterone Therapy Treatment | Ageonics Medical

Hypogonadism is the underproduction of sex hormones by the gonads, or sex organs. Male hypogonadism refers to the underproduction of testosterone, which can severely limit a growing boys sexual development and frustrate an adult males quality of life.

The easiest way to understand the effects of hypogonadism is to understand the effects of proper testosterone levels in a mans development. The male sex hormone contributes to everything from the deepening of the voice, the growth of body hair, and muscle building to sex drive and general self confidence. A lack of testosterone has the opposite effect, and can contribute to a higher-pitched voice, loss of body hair, muscle loss, lowered sex drive, and decreased confidence.

Hypogonadism can occur as early as fetal development, which may lead to androgyny, but male hypogonadism in particular can also occur as a result of testicular injury. Hypogonadism sustained before puberty is particularly problematic, as it will greatly affect puberty. Low testosterone during puberty can lead to:

Hypogonadism that occurs after puberty is less obvious, but can also lead to major problems, such as:

While these are some of the physical symptoms of hypogonadism, it is worth noting that hypogonadism, no matter when it occurs, can also lead to persistent psychological and emotional duress. Common stressors that accompany male hypogonadism may include:

Areas Low Testosterone Can Affect

Many adult males who have gone through puberty normally but experience hypogonadism in later life may not recognize its symptoms. If you suspect that you may be suffering from hypogonadism, testosterone replacement therapy is a potential treatment option. The pervasive symptoms of hypogonadism are caused in large part by low testosterone, and testosterone replacement therapy can greatly improve quality of life and sex drive.

Dr. Olivieri has many decades of experience treating men with low testosterone, and has helped thousands of men experience the benefits of normal testosterone levels, improving their lives, marriages, and mobility. If you know someone who may be suffering from hypogonadism or low testosterone in general, consider calling Aegonics Medical for a consultation.

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Hypogonadism, Male | ARUPConsult Lab Test Selection

Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM, Task Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010; 95(6): 2536-59. PubMed

Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Sep 2017]

Dean JD, McMahon CG, Guay AT, Morgentaler A, Althof SE, Becher EF, Bivalacqua TJ, Burnett AL, Buvat J, Meliegy AE, Hellstrom WJ, Jannini EA, Maggi M, McCullough A, Torres LO, Zitzmann M. The International Society for Sexual Medicine’s Process of Care for the Assessment and Management of Testosterone Deficiency in Adult Men. J Sex Med. 2015; 12(8): 1660-86. PubMed

Dohle G, Arver S, Bettocchi C, et al. Guidelines on male hypogonadism. European Association of Urology. Arnhem (the Netherlands) [Accessed: Jun 2017]

Kushnir MM, Blamires T, Rockwood AL, Roberts WL, Yue B, Erdogan E, Bunker AM, Meikle W. Liquid chromatography-tandem mass spectrometry assay for androstenedione, dehydroepiandrosterone, and testosterone with pediatric and adult reference intervals. Clin Chem. 2010; 56(7): 1138-47. PubMed

Morales A, Bebb RA, Manjoo P, Assimakopoulos P, Axler J, Collier C, Elliott S, Goldenberg L, Gottesman I, Grober ED, Guyatt GH, Holmes DT, Lee JC, Canadian Mens Health Foundation Multidisciplinary Guidelines Task Force on Testosterone Deficiency. Diagnosis and management of testosterone deficiency syndrome in men: clinical practice guideline. CMAJ. 2015; 187(18): 1369-77. PubMed

Paduch DA, Brannigan RE, Fuchs EF, Kim ED, Marmar JL, Sandlow JI. The laboratory diagnosis of testosterone deficiency. Urology. 2014; 83(5): 980-8. PubMed

Seftel AD, Kathrins M, Niederberger C. Critical Update of the 2010 Endocrine Society Clinical Practice Guidelines for Male Hypogonadism: A Systematic Analysis. Mayo Clin Proc. 2015; 90(8): 1104-15. PubMed

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ASH Physician-Scientist Career Development Award

The application cycle is now open.

The Physician-Scientist Career Development Award provides an opportunity for first-, second-, and third-year medical students to gain experience in hematology research under the mentorship of an ASH member and to learn more about the specialty. Awardees must agree to spend more than 80 percent of their time, during the immersive, year-long project, conducting laboratory, translational, or clinical hematology research.

The award provides recipients with $42,000 of funding for a one-year period. This includes $32,000 to support the trainee, $4,000 for research supplies, $4,000 for insurance and educational expenses (including one course), and $2,000 for meeting attendance (including the ASH annual meeting).

Award recipients attend the ASH annual meeting in December following their research experience. During an orientation breakfast, members of the ASH Committee on Training and Trainee Council are available to discuss specific areas of research and to provide recommendations on annual meeting sessions, events, abstracts, and/or posters related to the awardees areas of interest. Awardees are also invited to attend the Career Development Reception on Monday evening.

Jump To:

SelectTimelineEligibility RequirementsApplication ProcessEvaluation, Selection, and NotificationTerms and Conditions Questions

At the time of application, the applicant must:

The following individuals are not eligible to apply:

Physician-Scientist Career Development Award mentors must be ASH members who will assume the responsibilities of overseeing the award recipients work and progress. Mentors assist in completing the program application, aid the recipient in his/her research, and ensure that the recipient meets all deadlines, including those for award reports.

ASH believes that a multiple mentorship model is important for researchers regardless of their career stage. Therefore, the applicant may include a second mentor in his/her application to provide advice and career development support as well as additional guidance on research questions. If the study section believes additional mentorship may be beneficial to the applicant, members of the study section will be responsible for identifying an appropriate mentor and facilitating contact. The additional mentor will coordinate with the research mentor to the extent that is feasible and desirable.

The Physician-Scientist Career Development Award application, as well as all supporting documents outlined below, must be submitted through the ASH online awards system.

Required Documents

For more information about the required materials, please see the Required Documents PDF.

Applications submitted by the deadline will be reviewed by the Physician-Scientist Career Development Award study section. Applicants will be evaluated on the following criteria:

There is no limit to the number of applications that an institution and its affiliates can submit. However, no more than one award will be granted for any given institution. For this purpose, ASHs definition of medical school encompasses all affiliate institutions (e.g., University of Washington would include the Fred Hutchinson Cancer Research Center, Seattle Children’s Hospital, etc.).

All awards will be activated on July 1 of the award year and will conclude on June 30 of the following year (off-cycle exceptions may be allowed with explanation). Payment will be made in two equal installments (on July 1 and on January 1) to the institution at which the recipient will conduct his/her research. Research award funds are non-transferable.

As a condition of acceptance of the Physician-Scientist Career Development Award, it is required that:

After the award period, recipients are required to submit a final written report (not to exceed four pages). The report will include a summary of research, manuscript submissions during the award period related to the funded research, presentations (locally and nationally) of the funded research during the award period, educational goals met, and a summary of the usage of funds. This report must be emailed to Members of the Oversight Committee will evaluate final reports.

Please note: Failure to submit the final report or an interim progress report will render the applicant ineligible for future ASH funding.

Students making significant progress may submit a written request to reapply for one additional year of funding. Award renewal requests should be submitted by the award deadline. As part of the request, a joint letter must be submitted by the awardee and his/her mentor addressing the following:

No-cost extensions may be requested if needed. To request an extension, the awardees mentor should submit a letter to ASH by emailing the Awards Department at

Any funding not spent by the end of the award term must be returned to the Society when submitting the final report. A check made out to American Society of Hematology must be sent to the address listed below:

Allie SamisAwards Programs SpecialistAmerican Society Hematology2021 L Street NW, Suite 900Washington, DC 20036

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Everything You Need to Know About CRISPR, the New Tool that …

CRISPR, a new genome editing tool, could transform the field of biologyand a recent study on genetically-engineered human embryos has converted this promise into media hype. But scientists have been tinkering with genomes for decades. Why is CRISPR suddenly such a big deal?

The short answer is that CRISPR allows scientists to edit genomes with unprecedented precision, efficiency, and flexibility. The past few years have seen a flurry of firsts with CRISPR, from creating monkeys with targeted mutations to preventing HIV infection in human cells. Earlier this month, Chinese scientists announced they applied the technique to nonviable human embryos, hinting at CRISPRs potential to cure any genetic disease. And yes, it might even lead to designer babies. (Though, as the results of that study show, its still far from ready for the doctors office.)

In short, CRISPR is far better than older techniques for gene splicing and editing. And you know what? Scientists didnt invent it.

CRISPR is actually a naturally-occurring, ancient defense mechanism found in a wide range of bacteria. As far as back the 1980s, scientists observed a strange pattern in some bacterial genomes. One DNA sequence would be repeated over and over again, with unique sequences in between the repeats. They called this odd configuration clustered regularly interspaced short palindromic repeats, or CRISPR.

This was all puzzling until scientists realized the unique sequences in between the repeats matched the DNA of virusesspecifically viruses that prey on bacteria. It turns out CRISPR is one part of the bacterias immune system, which keeps bits of dangerous viruses around so it can recognize and defend against those viruses next time they attack. The second part of the defense mechanism is a set of enzymes called Cas (CRISPR-associated proteins), which can precisely snip DNA and slice the hell out of invading viruses. Conveniently, the genes that encode for Cas are always sitting somewhere near the CRISPR sequences.

Here is how they work together to disable viruses, as Carl Zimmer elegantly explains in Quanta:

As the CRISPR region fills with virus DNA, it becomes a molecular most-wanted gallery, representing the enemies the microbe has encountered. The microbe can then use this viral DNA to turn Cas enzymes into precision-guided weapons. The microbe copies the genetic material in each spacer into an RNA molecule. Cas enzymes then take up one of the RNA molecules and cradle it. Together, the viral RNA and the Cas enzymes drift through the cell. If they encounter genetic material from a virus that matches the CRISPR RNA, the RNA latches on tightly. The Cas enzymes then chop the DNA in two, preventing the virus from replicating.

There are a number Cas enzymes, but the best known is called Cas9. It comes from Streptococcus pyogenes, better known as the bacteria that causes strep throat. Together, they form the CRISPR/Cas9 system, though its often shortened to just CRISPR.

Top image: Screenshot from this MIT video explaining CRISPR

As this point, you can start connecting the dots: Cas9 is an enzyme that snips DNA, and CRISPR is a collection of DNA sequences that tells Cas9 exactly where to snip. All biologists have to do is feed Cas9 the right sequence, called a guide RNA, and boom, you can cut and paste bits of DNA sequence into the genome wherever you want.

DNA is a very long string of four different bases: A, T, C, and G. Other enzymes used in molecular biology might make a cut every time they see, say, a TCGA sequence, going wild and dicing up the entire genome. The CRISPR/Cas9 system doesnt do that.

Cas9 can recognize a sequence about 20 bases long, so it can be better tailored to a specific gene. All you have to do is design a target sequence using an online tool and order the guide RNA to match. It takes no longer than few days for the guide sequence to arrive by mail. You can even repair a faulty gene by cutting out it with CRISPR/Cas9 and injecting a normal copy of it into a cell. Occasionally, though, the enzyme still cuts in the wrong place, which is one of the stumbling blocks for wider use, especially in the clinic.

Mice whose genes have been altered or knocked out (disabled) are the workhorses for biomedical research. It can take over a year to establish new lines of genetically-altered mice with traditional techniques. But it takes just few months with CRISPR/Cas9, sparing the lives of many mice and saving time.

Traditionally, a knockout mouse is made using embryonic stem (ES) cells. Researchers inject the altered DNA sequence into mouse embryos, and hope they are incorporated through a rare process called homologous recombination. Some of first generation mice will be chimeras, their bodies a mixture of cells with and without the mutated sequence. Only some of the chimeras will have reproductive organs that make sperm with mutated sequence. Researchers breed those chimeras with normal mice to get a second generation, and hope that some of them are heterozygous, aka carrying one normal copy of the gene and one mutated copy of the gene in every cell. If you breed two of those heterozygous mice together, youll be lucky to get a third generation mouse with two copies of the mutant gene. So it takes at least three generations of mice to get your experimental mutant for research. Here it is summarized in a timeline:

But heres how a knockout mouse is made with CRISPR. Researchers inject the CRISPR/Cas9 sequences into mouse embryos. The system edits both copies of a gene at the same time, and you get the mouse in one generation. With CRISPR/Cas9, you can also alter, say, fives genes at once, whereas you would have to had to go that same laborious, multi-generational process five times before.

CRISPR is also more efficient than two other genome engineering techniques called zinc finger nuclease (ZFN) and transcription activator-like effector nucleases (TALENs). ZFN and TALENs can recognize longer DNA sequences and they theoretically have better specificity than CRISPR/Cas9, but they also have a major downside. Scientists have to create a custom-designed ZFN or TALEN protein each time, and they often have to create several variations before finding one that works. Its far easier to create a RNA guide sequence for CRISPR/Cas9, and its far more likely to work.

Most science experiments are done on a limited set of model organisms: mice, rats, zebrafish, fruit flies, and a nematode called C. elegans. Thats mostly because these are the organisms scientists have studied most closely and know how to manipulate genetically.

But with CRISPR/Cas9, its theoretically possible to modify the genomes of any animal under the sun. That includes humans. CRISPR could one day hold the cure to any number of genetic diseases, but of course human genetic manipulation is ethically fraught and still far from becoming routine.

Closer to reality are other genetically modified creaturesand not just the ones in labs. CRISPR could become a major force in ecology and conservation, especially when paired with other molecular biology tools. It could, for example, be used to introduce genes that slowly kill off the mosquitos spreading malaria. Or genes that put the brakes on invasive species like weeds. It could be the next great leap in conserving or enhancing our environmentopening up a whole new box of risks and rewards.

With the recent human embryo editing news, CRISPR has been getting a lot of coverage as a future medical treatment. But focusing on medicine alone is narrow-minded. Precise genome engineering has the potential to alter not just us, but the entire world and all its ecosystems.

More Reading:

Breakthrough DNA Editor Borne of Bacteria Quanta, Carl Zimmer

A CRISPR For-CAS-t The Scientist, Carina Storrs

Genetically Engineering Almost Anything NOVA NEXT, Tim De Chant and Eleanor Nelsen

This post has been updated to clarify that the the number of basepairs in guide RNA for CRISPR/Cas9 is different from the number of basepairs it recognizes in a target sequence.

Contact the author at

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Stem Cells Repair Heart in First-Ever Study –

Nov. 14, 2011 — The first use of heart stem cells in humans looks like a major breakthrough for people suffering heart failure after heart attacks.

It’s early — results are in for only the first 16 patients — but the results already are drawing praise from experts not easily impressed by first reports.

“This is a groundbreaking study of extreme importance,” Joshua Hare, MD, director of the University of Miami’s Interdisciplinary Stem Cell Institute, tells WebMD via email. Hare was not involved in the study.

“The reported benefits are of an unexpected magnitude,” writes Gerd Heusch, MD, PhD, chair of the Institute of Pathophysiology at the University of Essen, Germany, in an editorial in the Nov. 14 online issue of The Lancet.

Study researcher John H. Loughran, MD, of the University of Louisville, Ky., could barely contain his excitement in an interview with WebMD.

“The improvement we have seen in patients is quite encouraging,” he says. “Michael Jones, our first patient, could barely walk 30 feet [before treatment]. I saw him this morning. He says he plays basketball with his granddaughter, works on his farm, and gets on the treadmill for 30 minutes three times a week. It is stories like that that makes these results really encouraging.”

The breakthrough comes just as researchers were becoming discouraged by studies in which bone-marrow stem cells failed to heal damaged hearts.

Instead of getting stem cells from the bone marrow, the new technique harvests stem cells taken from the patients’ own hearts during bypass surgery. Just 1 gram of heart tissue — about 3.5 hundredths of an ounce — is taken.

Using a technique invented by Brigham & Women’s Hospital researchers Piero Anversa, MD, and colleagues, heart stem cells are taken from the tissue and grown in the lab. These adult stem cells already are committed to becoming heart cells, but they can transform into any of the three different kinds of heart tissues.

It’s the first time tissue-specific stem cells, other than bone-marrow cells, have been tested in humans, Hare says.

In the study, about a million of the cells were infused into each patient’s heart with a catheter. Calculations suggest that each of these infused cells could generate 4 trillion new heart cells.

The study was designed to show whether the technique was safe. It was: No harmful effects have been seen. But to the researchers’ surprise, the relatively small number of cells infused into patients had a major effect.

Of the 14 patients analyzed so far, heart function improved dramatically. And in the eight patients seen one year after treatment, improvement appears to have continued. Moreover, the scars on patients hearts — areas of dead tissue killed during their heart attacks — are healing.

And patients aren’t just doing better on measures of heart function. Like Michael Jones, they report vastly improved quality of life and ability to perform daily tasks.

“Now this is an open-label trial, so patients know they are treated. This means we have to take what they say with a grain of salt,” Loughran says. “But we see these patients not only are feeling better but doing more.”

The only downside of this early success is that the ongoing study already has enrolled all 20 of the patients who will be treated. The experimental treatment simply will not be available to other patients in the near future. A larger, phase II study is planned.

“All the patients that call in to us, and there are quite a few interested, we encourage them to maintain close contact with their doctors,” Loughran says. “Lifestyle changes and medical management are the most important things for them right now. We will be working very hard to get new trials under way.”

The findings were reported at the American Heart Associations Scientific Sessions meeting in Orlando, Fla., and in the Nov. 14 online edition of The Lancet.


John H. Loughran, MD, fellow in cardiovascular medicine, University of Louisville, Ky.

Joshua Hare, MD, director, Interdisciplinary Stem Cell Institute, University of Miami.

Bolli, R. The Lancet, published online Nov. 14, 2011.

Heusch, G. The Lancet, published online Nov. 14, 2011.

Traverse, J.H. Journal of the American Medical Association, published online Nov. 14, 2011.

Hare, J. Journal of the American Medical Association, published online Nov. 14, 2011.

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CRISPR Gene Editing and the DNA of Future Food | Digital Trends

Agriculture has come a long way in the past century. We produce more food than ever before but our current model is unsustainable, and as the worlds population rapidly approaches the 8 billion mark, modern food production methods will need a radical transformation if theyre going to keep up. But luckily, theres a range of new technologies that might make it possible. In this series, well explore some of the innovative new solutions that farmers, scientists, and entrepreneurs are working on to make sure that nobody goes hungry in our increasingly crowded world.

Corn isnt the sexiest crop but its one of the most important. Its the most abundant grain on Earth, used as food and biofuel around the globe. In ancient times, Mesoamericans thrived on it, waged wars over it. Their myths claimed corn was the matter from which gods created mankind itself.

But, just as corn helped create these civilizations, these civilizations helped create corn through meticulous selective breeding. Todays grain hardly resembles its ancestors. Compared to the wild plant first cultivated by ancient Mexicans some ten thousand years ago, modern corn is a super mutant.

And yet, after all those thousands of years of cultivation, just two main genes are thought to be responsible for the evolution of the corn we eat today. Selective breeding is painstakingly slow and imprecise.

But thats all about to change.

Selective breeding is painstakingly slow and imprecise. But thats all about to change.

New gene editing tools like CRISPR/Cas9 now let scientists hack into genomes, make precise incisions, and insert desired traits into plants and animals. Well soon have corn with higher crop yields, mushrooms that dont brown, pigs with more meat on the bone, and disease resistant cattle. Changes that took years, decades, or even centuries, can now be made in a matter of months. In the next five years you might eat tortilla chips made from edited corn. By 2020 you might drink milk from an edited cow.

Dubbed the CRISPR Revolution these scientific advances in gene editing have huge potential that many experts think could help fortify our food system and feed an increasing population of farmers who are threatened by food scarcity caused, in part, by climate change.

But not everyone is so certain. Beyond the contentious legal battles that have thus far complicated CRISPR science, calling into question who can and cant use the technology, some consumer rights advocates think these tools will be used to maintain the status quo of an industry based primarily on corporate profit. Meanwhile, residual worry about genetically modified organisms (GMOs) may influence the public perception of gene-edited organisms, steering consumers towards the organic aisle despite scientific evidence.

Gene editing is, simply put, the act of making intentional changes to DNA in order to create an organism with a specific trait or traits. Its like using a word processor to edit the words in a sentence. Geneticists insist we dont confuse this with genetic modification (otherwise called genetic engineering), which introduces new genes from different species in order to achieve desired traits. The difference may sound trivial but experts say it could help calm the concerns associated with GMOs.

Consider this simplification. We have the sentence, The cat has a hat, but want to be more descriptive about the hats color. With modification, we would borrow the German word for black and write, The cat has a schwarz hat. The sentence makes sense (sort of) but its obvious that to some people it would be problematic and maybe even an improper use of language. With editing, we dont have to borrow a word from another language. We instead just insert the English word and write, The cat has a black hat.

In the older, more traditional system, scientists were taking a gene from one species and putting it into a plant to confer a particular trait on that plant, Rachel Haurwitz, co-founder of Caribou Biosciences, told Digital Trends. Thats not what were looking to do. Were looking to use CRISPR gene editing to achieve the same outcome as we can get from traditional breeding, just faster.

This ability to edit with such speed and precision is still relatively new, and due largely to CRISPR, which emerged straight from nature to become the most popular and powerful gene editing tool used today. Discovered in bacteria in the late eighties, it wasnt until 2005 that researchers began to unravel its role. Scientists found that when certain bacteria come under attack from viruses, they use special enzymes to cut, copy, and save a bit of the viral DNA. Later, if the intruder returns, the bacteria can quickly recognize it and react to defend itself.

A few years later, researchers realized this system could be used to cut and edit the DNA of any organism, not just viruses. In 2012, Jennifer Doudna and Emmanuelle Charpentier published the first paper demonstrating how CRISPR can be used to edit an organisms genome.

Were looking to use CRISPR gene editing to achieve the same outcome as we can get from traditional breeding, just faster.

Not only is this technique far cheaper, faster, and more precise than conventional genetic modification, it avoids many (if not all) of the issues raised by skeptics, whose main concerns point toward the creation of transgenic organisms.

But, whereas genetic modification entails combining DNA from multiple species, gene editing entails altering the DNA of one species with a trait that already exists naturally.

Gene editing is not at all about taking DNA from a foreign species and integrating it into a plant, Haurwitz said. Its really about working within the constraints of the plants own genome.

Just over four years ago, Haurwitz founded Caribou as a spin off from Doudnas lab at the University of California, Berkeley. Since then, her team has partnered with companies around the world, providing licensing rights to use the startups version of the gene editing tool. One of those partnerships may see the first CRISPR-edited organism come to market via DuPont Pioneer, one of the worlds biggest chemical companies.

The day before Halloween 2015, Yinong Yang submitted an Am I Regulated letter to the United States Department of Agricultures (USDA) Animal and Plant Health Inspection Service (APHIS). He and his colleagues at Penn State had used CRISPR to knock out a gene in white button mushrooms that makes them go brown over time. Without the browning gene, white buttons look better and last longer, and Yang wanted to know whether his mushrooms could legally go to market.

The following spring, the departments response resonated throughout the scientific and agricultural community. APHIS does not consider CRISPR/Cas9-edited white button mushroomsto be regulated, it wrote in an open letter.

Last year, researchers at DuPont Pioneer, the agriculture branch of the multi-billion-dollar conglomerate DuPont, published a study about a strain of corn engineered with CRISPR to be more resistant to drought. Its one of several CRISPR-modified crops that may soon be coming to market.

It was a landmark decision. Yangs mushrooms were the first gene-edited crop cleared for commercial sale by the USDA, which made a clear distinction between genetic modification and gene editing, and set a precedent for those to come.

A few days later, DuPont the fourth largest chemical corporation in the world received a similar response from the USDA regarding its CRISPR-edited waxy corn thats disease resistant and drought tolerant. DuPont wasted no time announcing plans to take its crop to market within the next five to ten years.

The USDA has said these products do not fall into their remit, as their remit is really focused on, say, plant pathogens or noxious weeds, said Haurwitz, whose company provides DuPont with its CRISPR technology. At the same time were seeing the FDA put out a call for information as theyre looking at their own remit to oversee the entire food supply, not just products made with modern biotechnology. And I think theyre looking to members of the scientific and business communities to really weigh in over the next few months.

Unlike most Button mushrooms, these ones dont brown or develop blemishes from being handled. This trait doesnt occur naturally it happens because the gene that makes the mushrooms turn brown was selectively removed from them via the CRISPR/Cas9 method. (Photo: Yang Lab)

For Yangs part, he intends to improve his mushrooms before making them commercially available. Although not legally required, he plans to seek approval from the Food and Drug Administration (FDA) and Environmental Protection Agency (EPA).

Edited waxy corn may find its way into the food system much sooner than white button mushrooms, if not as human food than as fodder for the growing number of livestock around the world. Meanwhile, these livestock are also undergoing genetic edits as researchers use the same tools to make animals healthier, meatier, and more productive.

Pigs harbor a lot of diseases and there are few as bad as porcine reproductive and respiratory syndrome (PRRS). It causes pregnant mothers to miscarry and makes it difficult for piglets to breathe. Its a problem for the pig farmers as well. Every year, the PRRS virus costs the industry nearly $1.6 billion dollars in Europe and another $664 million in the US.

The impacts of the disease for producers are often devastating, said Jonathan Lightner, Chief Scientific Officer at biotech company Genus. And the impacts on the animals themselves are terrible.

If we could integrate the polled phenotype into the dairy system, that would eliminate dehorning for at least seven or eight million animals a year.

But Lightner and his team are working on a solution. In December 2015, scientists at Genus and the University of Edinburghs Roslin Institute demonstrated how CRISPR could remove the CD163 molecule, a pathway through which the PRRS virus infects pig. Just last month, the researchers refined their work to remove just the portion of the gene that directly interacts with the virus. Lab tests, as published in a paper in the journal PLOS Pathogens, have shown that DNA in cells removed from these pigs successfully resist the virus. Next steps in the study will test whether the pigs themselves are resistant to the virus.

Swine are also the subject of research at Seoul National University in South Korea, where scientists led by Jin-Soo Kin are using a different gene-editing tool called TALEN to create meatier, double muscle pigs by removing a gene that inhibits muscle growth. We could do this through breeding, Kin told Nature back in 2015, but then it would take decades.

In fact, farmers have developed similar traits through breeding Belgian Blues, a type super-sculpted beef cattle prized for its lean meat and beefy build. It took over a hundred years to establish those traits in the breed.

Researchers at University of California, Davis and a startup called Recombinetics are using the same TALEN gene editing technique to cut decades down to days, removing the horned gene from common dairy cows and inserting the one that makes Angus beef cattle naturally dehorned or polled. Polled cattle are desirable because they pose less threat to their handlers and to each other. But, as Tad Sonstegard, Chief Science Officer of Acceligen (a Recombinetics subsidiary) explained, polled cattle in certain breeds are simply less productive.

Gene editing ala CRISPR/Cas9 has allowed scientists to not only produce polled (hornless) cows, but also cows that are immune to common diseases, such as tuberculosis. (Photo: Gregory Urquiaga/UC Davis)

The issue is that the top [dairy] bulls that everyone wants are horned, Sonstegard said. The animals that are polled that already exist have a difference of about $250 over their lifetime. If youre running a thousand head dairy [operation], thats a lot of money.

What many ranchers do instead is dehorn their cattle, a stressful practice when anesthesia is used, a painful practice when it isnt, and a significant expense for the ranchers either way.

If we could integrate the polled phenotype into the dairy system, that would eliminate dehorning for at least seven or eight million animals a year, Sonstegard said. If you include beef, thats up to fifteen million.

Recombinetics has already bred a couple gene-edited calves, which are undergoing care and monitoring at UC Davis. But, before any gene-edited cows produce the milk in our grocery stores, Sonstegard said scientists would need to prove that milk from these cows is similar to horned and polled cows that havent been gene edited. That would be simple though, he said, it would turn out the same.

As the global population grows, so does the demand for food. Meanwhile, farmers around the world face food scarcity generated in part by a changing climate that makes caring for plants and livestock an increasingly difficult task.

But CRISPR-like tools may be able to help.

On the plant side were looking at ways to breed plants that are more drought tolerant or in other ways can better survive the stresses of climate change, Haurwitz said. I think thats incredibly valuable and important as we look at the exploding global population. Caribou has also partnered with Genus in its project to breed PRRS virus resistant pigs.

Beyond his work at Recombinetics, Sonstegard sits on the scientific advisory board of the Centre for Tropical Livestock Genetics and Health, a Gates Foundation-backed initiative to improve the genetics of native livestock in tropical regions. Most productive livestock breeds cant survive the heat or diseases present in tropical environments, and breeds native to tropical environments havent had the same selective breeding programs that generate highly productive livestock.

Will CRISPR be used primarily for patenting foods in ways that fit in existing corporate profit models?

Most of the indigenous animals have not been under strict artificial selection, Sonstegard said. Its all been done anecdotally, since most farmers dont have that many cows and their systems arent that big. Meanwhile, most of the new DNA introduced to these herds is left over semen from bulls in developed countries, according to Sonstegard. Its cheap, he said, and no one in the developed country wants it anymore, so they ship it overseas.

There are a couple possible approaches to strengthening these indigenous breeds. One way would be to edit the DNA of bulls from productive breeds so that theyre more temperature tolerant and disease resistant within tropical climates. Those bulls could then be introduced to the native herds to reproduce and spread their productive genes. Alternatively, the DNA of indigenous bulls could be edited with genes likely to improve productivity of the herd, including milk production and carcass yield.

Right now the trend in those countries is that theres a linear growth in livestock numbers, Sonstegard said, because theyre not improving production but demand is increasing, so they just make more animals.Thats not sustainable.

Researchers are also using CRISPR to save dying and endangered species. This month some of Sonstegards colleagues published a paper showing they could develop surrogate hens that could help raise endangered species of birds. And in Florida, where an invasive disease known as citrus greening is decimating the states iconic orange industry, University of Florida scientists are using CRISPR to develop varieties of orange trees immune to the disease, according to the Tampa Bay Times.

But not everybody is so gung-ho.

UC Davis geneticist Alison Van Eenennaam, who collaborates with Recombinetics on gene-editing polled cows, is absolutely optimistic about the tool I think it can be used for very useful things, she said. Rather than ask why we should use, lets ask how. but shes also careful not to overstate the potential of gene editing. When asked whether the technology could be used to address world hunger, she said, I kind of think that idea is polyamorous. Show me anything that can magically solve world hunger. Lets not oversell this technology. Its useful but its useful for a fairly discreet purpose at this stage, which is making edits to a [gene] sequence that we know has a particular effect.

And CRISPR, of course, has its skeptics. Stacy Malkan, Co-Director of U.S. Right to Know, a nonprofit that calls for transparency and accountability in the food system, is both concerned about the inherent risk involved in gene editing and suspects it could ultimately perpetuate an already imbalanced food system.

Theres really no big difference between [gene editing] and conventional breeding.

Will CRISPR be used primarily for the purpose of patenting foods in ways that fit in existing corporate profit models, she asked, for example, to engineer commodity crops to withstand herbicides, or to engineer livestock to fit better in unhealthy confined feeding operations? Or will it be used to engineer foods that have consumer benefits? Will there be labeling, and safety assessments? There are many questions. Right now we hear a lot of marketing hype about possible benefits of CRISPR, but we heard the same promises about first-generation GMOs for decades and most of those benefits have not panned out.

For scientists like Van Eenennaam, the GMO discussion is over. Frankly, she said, Im over the debate. If someone isnt convinced by the evidence that every single major scientific society in the world says its safe, than nothing Im going to say is going to convince them any differently. When it comes to gene-edited organisms, most scientists are even more insistent about its safety. Theres really no big difference between [gene editing] and conventional breeding, Van Eenennaam added.

But there isnt complete consensus. Malkan points to an interview she recently had with Michael Hansen, senior scientist from Consumers Union, in which Hansen said of CRISPR-like gene editing tools, These methods are more precise than the old methods, but there can still be off-target and unintended effects. When you alter the genetics of living things they dont always behave as you expect. This is why its crucial to thoroughly study health and environmental impacts, but these studies arent required.

From Sonstegards perspective, mutations and off-target effects occur naturally anyway, and gene editing simply offers a more precise approach than selective breeding.

Still, Malkan and others have their reservations, grounded in the idea that its too early to determine the side effects. CRISPR is a powerful research tool for helping scientists understand genetics, how cells react, how entire plants and systems react, she said. In my view these experimental technologies should be kept in the lab, not unleashed in our food system, until those systems are better understood.

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Scientists successfully used CRISPR to fix a mutation that …

CRISPR/Cas9 is a gene editing technology thats revolutionizing science at a breathtaking pace.

One of its most exciting, taboo, and controversial applications is tweaking the genes of eggs, sperm, or early embryos to alter a human life. This could one day mean the ability to create smarter or more athletic humans (yes, designer babies), but also the chance to knock out disease-causing genetic mutations that parents pass on to their children. Were talking about eliminating mutations linked to diseases like breast and ovarian cancers or cystic fibrosis.

On Wednesday, a team of scientists reported that they have made major progress toward proving the latter is possible.

In a paper published in the prestigious journal Nature, a team led by Shoukhrat Mitalipov of Oregon Health and Science University described how it used CRISPR/Cas9 to correct a genetic mutation thats linked to a heart disorder called hypertrophic cardiomyopathy in human embryos. And they did it without the errors that have plagued previous attempts to edit human embryos with CRISPR.

To be clear, the new work from OHSU was an experiment the point was to test a concept, and the embryos used were never implanted into a womans uterus.

But the researchers were ultimately able to show that CRISPR/Cas9 can do what they hoped it would do. It cut the mutant gene sequence, prompted the embryos to repair the DNA with healthy copies of the gene, and eliminated the disease-causing mutation altogether from many of the embryos.

Lets pause for a minute and make sure were clear on what CRISPR/Cas9 is. You can read our full explainer here, but in a nutshell, its essentially a clever system built into bacterial DNA that allows them to recognize and fend off attackers, usually viruses. The way it works, as Brad Plumer described it, is that special enzymes in the CRISPR sequences known as Cas9 carry around stored bits of viral genetic code like a mug shot. When they find a match to the code, they will chop up the DNA and neutralize the threat.

The real breakthrough, which appeared in a series of landmark papers published in 2012 and 2013, was figuring out that it was possible to program CRISPR/Cas9 to find any kind of DNA code, not just viruses, and get the enzymes to snip it.

Mitalipov and colleagues created embryos in the lab with sperm from a carrier of the disease-causing mutation in the MYBPC3 gene, and eggs from 12 healthy donors. And they sent CRISPR/Cas9 into the fertilized egg.

As the embryos developed, they found that after CRISPR/Cas9 cut the sequence in the embryo DNA with the problematic gene. In most cases the embryos repaired the breaks with a healthy copy of the gene from the maternal donor.

In all, 36 out of 54 embryos ended up with mutation-free copies of MYBPC3. (Another, slight different round of the experiment yielded 42 out of 58 embryos with mutation-free copies of the gene.) Which means that had those embryos become children, the children would have had practically no chance of developing hypertrophic cardiomyopathy. Thats pretty significant since this a disease that affects one in 500 people and can cause sudden cardiac death and heart failure. If one parent has a mutant copy of MYBPC3, their child has a 50 percent chance of inheriting the condition.

These results are also promising for people (mainly older women and couples) who have a limited number of viable embryos to use to get pregnant with in vitro fertilization. Currently, reproductive medicine doctors use something called preimplantation genetic diagnosis, or PGD, to identify embryos with harmful mutations. And when they find embryos with mutations linked to disease, they often discard them, which can leave patients with few healthy embryos to try to transfer into the womb. (Transfer success rates are overall pretty low.)

The researchers say that in the future, their technique could be used with PGD to help fix the mutations in embryos that otherwise would be discarded, giving women and couples more embryos to transfer and a better chance of getting pregnant.

Were not ready for gene editing in embryos that would be implanted for pregnancy anytime soon. But this is a big advance because the researchers got stronger results than anyone who has ever tried to target disease-causing genes with CRISPR-Cas9 before.

And while the experiment focused only on this particular gene and disease, the researchers say they feel confident the technique would work for many of the thousands of other inherited disorders out there linked to one mutation because their approach has so far proved to be efficient, accurate, and safe.

But in a press conference on Tuesday, one of the co-authors, Paula Amato, an OB-GYN doctor at OHSU, stressed that many more safety tests would be needed before proceeding with a clinical trial. We want to replicate the study with other mutations and other [sperm and egg] donors, she said. In particular, she said shes interested in seeing if it works on BRCA1 and 2, mutations that increase the risk of breast and ovarian cancers.

Other researchers, including Nerges Winblad and Fredrik Lanner at Karolinska Institutet in Sweden, who wrote an accompanying article in Nature, are encouraged by the results but still cautious about the safety of the technology. They zeroed in on issues that have shown up in previous studies: off-target effects, or undesirable mutations in genome regions close to the targeted sequence, and mosaicism, where not all embryo cells make the desired changes. According to Winblad and Lanner, researchers will have to keep showing that they can reliably avoid these and other abnormalities in edited embryos before [the technology] can be used as a therapy for inherited diseases.

Amato and her co-authors said theres also plenty of room for other improvement. Some of their embryos DNA ended up with unintended additions or deletions. So their goal would be to get 80 to 90 percent of a large group of embryos mutation-free to ensure that the technique is reliable before attempting a clinical trial.

Again, this wasnt the first time scientists had tried to use CRISPR to edit human embryos. Chinese researchers have done it twice: once in 2015 to modify a gene linked to the blood disorder called beta thalassaemia, and then in 2016 to make genes resistant to HIV. But both of these experiments were smaller, and one used abnormal embryos while the other used immature eggs. And the results from both were messy, suggesting that embryo editing had a long, hard road ahead.

It was precisely those messy results, along with a host of other concerns, that prompted the Organizing Committee for the International Summit on Human Gene Editing at the National Academies of Sciences, Engineering, and Medicine to advise researchers in December 2015 to be extremely cautious about editing sperm, eggs, and embryos (known collectively as the human germline). Then in a report in February, it said clinical trials on human genome editing might one day be allowed, but in the meantime, researchers could attempt to correct mutations that cause a serious disease or condition and only when no reasonable alternatives exist. And definitely no research on enhancement of human traits like intelligence or strength for now.

At present, the US government does not fund any genomic editing of human embryos. (Mitalipov and his colleagues got funding from their university this new study.) And the Food and Drug Administration is prohibited by Congress from considering any clinical trials related to genetic editing of eggs, sperm, or embryos.

The impressive new findings in Nature raise huge questions about how the US should proceed with this field of research. How soon to allow clinical trials, for instance?

I believe [the National Academies] can reconsider what mutations and what cases the gene corrections can be used and must be used to allow clinical trials in the future to go forward, said Mitalipov. We may not be in agreement with the committees. The work is back and forth, and the committees hopefully will consider new options.

He added that hed be willing to move this research to the UK, if necessary. He also is sensitive about how his results are portrayed, given the American publics reticence, and in some cases fear, about genetic modification.

I dont like the word editing, he said. We didnt edit or modify anything. … We used CRISPR to correct, using existing maternal genes.

Other CRISPR researchers have weighed in about where the field should go from here.

In my opinion, we still need to respect the recommendations in the [National Academy of Sciences] report published in February that recommended refraining from clinical use of human germline editing until and unless theres broad societal consensus about the value, Jennifer Doudna, a UC Berkeley molecular biologist and a leading CRISPR researcher, told the Los Angeles Times.

It may be quite a while before a clinical trial is approved. In the meantime, any prospective parents who want to avoid passing on disease-causing genes to their kids will have to continue to use PGD during in vitro fertilization.

As weve reported, scientists from myriad fields are using CRISPR to try to grow better food, destroy viruses, and clean up the environment.

Hank Greely explains for Vox why in 20 to 40 years, most Americans wont have sex to reproduce.

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Scientists successfully used CRISPR to fix a mutation that …

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Hormone Replacement Therapy –

A few years ago, the use of hormone replacement therapy (HRT) looked like a medical mess. For decades, women were told that HRT — usually a combination of estrogen and progestin — was good for them during and after menopause. Then the 2002 results of the Women’s Health Initiative study seemed to show just the opposite: hormone replacement therapy actually had life-threatening risks such as heart attacks, strokes, and cancer.

“Women felt betrayed,” says Isaac Schiff, MD, chief of obstetrics and gynecology at Massachusetts General Hospital in Boston. “They were calling their doctors, saying, ‘How could you put me on this drug which causes heart attacks, strokes, and cancer?'”

Almost overnight, standard medical practice changed. Doctors stopped prescribing hormone replacement therapy and 65% of women on HRT quit, according to Schiff.

But some experts say hormone replacement therapy may be coming back. All along HRT remained an important treatment for menopause symptoms like hot flashes. And now, a number of recent studies show that hormone replacement therapy may have protective benefits for women who are early in menopause.

“I think we swung too positive on hormone therapy in the past and then we went too negative,” says Schiff, who is also chair of the American College of Obstetricians and Gynecologists Task Force on Hormone Therapy. “Now we’re trying to find a balance in between.”

“We’re definitely in a gray zone of uncertainty about hormone therapy,” says Jacques Rossouw, MD, project officer for the federal Women’s Health Initiative (WHI). “But when you’re uncertain, you have to err on the side of safety.”

While Rossouw concedes that new studies show some preventative benefit for younger women, he says any potential benefit is very slight. And, he notes, there is no evidence that any benefit would last if women kept taking hormones as they got older.

But increasing numbers of researchers say there should be a place for hormone replacement therapy as a preventive treatment for limited periods as it may help prevent disease in younger women around the age of menopause.

“We have evidence that hormone therapy can prevent heart disease, hip fractures, and osteoporosis, and that it cuts the risk of developing diabetes by 30% in younger women,” says Shelley R. Salpeter, MD, a clinical professor of medicine at Stanford University’s School of Medicine.

In one recent study, Salpeter and her colleagues found that HRT reduced the number of heart attacks and cardiac deaths by 32% in women who were 60 or younger (or women who had been through menopause less than 10 years ago). In older women, hormone replacement therapy seemed to increase cardiac events in the first year, and then began to reduce them after two years.

The 32% drop is significant, but perhaps not as dramatic as it sounds. In hard numbers, Salpeter estimates that of women aged 50 to 59 who don’t get hormone replacement therapy, about 7 out of 4,800 will have a cardiac event in one year. With HRT, 3 out of 4,800 will have a cardiac event.

Salpeter’s study indicates something crucial: The age at which a woman starts HRT may make a big difference.

Salpeter argues that when a person first starts hormone replacement therapy, her risk of blood clots increases slightly. In healthy women who are in their 50s — and close to the age of menopause — this increase is very unlikely to cause problems. The higher risk subsides after a couple of years, she says, although other experts disagree.

But women in their 60s may be more likely to already have early heart disease or hardening of the arteries (arteriosclerosis). In these cases, the risk of blood clots becomes more serious. So if a woman first starts hormone replacement therapy in her 60s, the initial risks are more dangerous, Salpeter says.

This is what Salpeter says affected the results of the Women’s Health Initiative trial. The average age of a woman in that trial was 63, with a range of ages between 50 and 79. She and other critics argue that the researchers were looking at many women who might already have been sick.

“I was surprised when I first heard the [WHI] results,” says Lynne T. Shuster, MD, director of the Women’s Health Clinic at the Mayo Clinic in Rochester, Minn. “But, once I saw the details, I wasn’t surprised anymore. They gave women who were older and possibly had underlying arteriosclerosis a pill that increased the risk of blood clotting. Of course it increased the risk of heart problems.”

Shuster and Salpeter argue that those results have no bearing on whether younger, healthy women in their 50s would benefit from HRT.

“Basically, [the WHI researchers] were looking at the wrong group of people,” Salpeter tells WebMD.

Rossouw defends the WHI study design. “We were specifically testing the hypothesis that hormone therapy would help protect older women against disease,” Rossouw tells WebMD, “The results were absolutely clear: They do not.”

Media reports on the WHI results may have given people inflated fears of hormone replacement therapy’s risks, the doctors say.

For example, the Women’s Health Initiative results showed that combined hormone replacement therapy seems to increase the risk of breast cancer by 33%, Schiff says. That’s a serious increase. Still, the risk to any one woman is not as high as it sounds, Schiff says.

“According to the WHI, without hormone therapy, 3 of every 1,200 women aged 55 to 59 will develop breast cancer this year,” says Schiff. “With hormone therapy, 4 out of 1,200 will. It’s a 33% increase, but the absolute risk is still very, very small.”

Shuster points out that other behaviors — like drinking two glasses of wine a night — also increase breast cancer risk by a similar amount.

Women who take estrogen alone — a treatment only available to people who have had a hysterectomy — appear to have a lower risk of developing breast cancer than women who take progestin and estrogen together. In a 2006 JAMA article, researchers from the Women’s Health Initiative found that after about seven years of treatment with estrogen, there seemed to be no increased risk of breast cancer.

However, estrogen-only therapy may have long-term risks. A May 2006 study published in the Archives of Internal Medicine found using estrogen-only therapy for 20 years or more showed increased risk of developing breast cancer.

As HRT is being re-evaluated — and new evidence is coming in — it’s difficult to know who should get hormone replacement therapy and for how long.

The U.S. Food and Drug Administration (FDA) recommends that HRT should be used in women who have severe menopausal symptoms.

“Estrogens are the best agents we have for the relief of menopausal symptoms like hot flashes, vaginal dryness, and loss of sexuality,” says Schiff. They’re also a good treatment for menopausal symptoms that are often not recognized: Difficulty sleeping, stiffness, joint pain, and mood changes.

But for disease prevention — lowering the risk of heart attacks, strokes, and most cases of osteoporosis — the FDA still does not recommend hormone replacement therapy.

“We have other ways of cutting the risks of heart attacks and strokes,” Schiff tells WebMD, including better diet, exercise, and other medicines.

Will HRT ever again be used as prevention for these serious diseases? Only time and research will tell. The experts remain divided.

“I believe that studies in the next few years will support using hormone therapy in younger women [closer to the onset of menopause] for prevention,” says Shuster. “But “we don’t have all the information yet.”

Another big question is how long hormone replacement therapy can be used safely. It was once thought that using it for five years or less to relieve menopausal symptoms had no risks. But the WHI study seemed to show that was not the case.

There are still a lot of unknowns. Many women now take doses of hormones that are lower than the ones used in the WHI trial. Hormones are also delivered not just through pills, but in other forms, like skin patches. We don’t know yet whether these lower concentrations and different forms might decrease the risks.

For now, the FDA recommends that women who take hormone replacement therapy for menopausal symptoms take the lowest effective dose and for the shortest time period to alleviate symptoms.

With all of the contradictory messages, it’s hard for a woman to know what to do. There’s also a lot of lingering anger about what happened in the wake of the Women’s Health Initiative results.

“I lost a lot of faith in my doctors after that,” says April Dawson, a 63-year-old Connecticut woman who used hormone replacement therapy for about a year. “And all of the women I know feel the same way.

“In the first place, I didn’t like the idea of going on medication when I didn’t have any symptoms,” Dawson tells WebMD. “But I feel like my doctors ganged up on me and pushed me to take it.”

Today, doctors are far more likely to tell each woman that she must make the decision herself, weighing the pros and cons of hormone replacement therapy, considering her symptoms, family history, lifestyle, and risk of disease.

If you take HRT, keep in mind that the absolute risks are low. But you should still regularly check in with your doctor. Ask if there is any new information that might cause you to rethink your decision.

“Hormone therapy is a field that continues to change rapidly,” says Shuster. “Treatment has to be more individualized than ever. Women are seeking the one right answer, but for now, we just don’t have one.”

SOURCES: American College of Obstetricians and Gynecologists web site,”Frequently Asked Questions about Hormone Therapy, “News release: ACOG IssuesState-of-the-Art Guide to Hormone Therapy.” Chen, WY et al, Archives ofInternal Medicine, May 8, 2006; vol 166: pp1027-1032. April Dawson,Milford, Conn. Jacques Rossouw, MD, project officer for the Women’s HealthInitiative at the National, Heart, Lung and Blood Institute, Bethesda, MD.Salpeter, SR et al, JGIM, July 2004; vol 21: pp 363-366. Salpeter, S,Climacteric 2005; vol 8: pp307-310. Salpeter, SR et al, Diabetes,Obesity and Metabolism, in press. Salpeter, SR et al, Journal ofGeneral Internal Medicine, July 2004; vol 19: pp 791-804. Shelley R.Salpeter, MD, clinical professor of medicine at Stanford University’s School ofMedicine. Isaac Schiff, MD, chief of obstetrics and gynecology at MassachusettsGeneral Hospital in Boston; chair of the American College if Obstetricians andGynecologists Task Force on Hormone Therapy. Lynne T. Shuster, MD, director ofthe Women’s Health Clinic at the Mayo Clinic in Rochester, MN. Stefanick, ML etal, JAMA, April 12, 2006; vol 295: pp 1647-1657. U.S. Food and DrugAdministration web site, “Questions and Answers for Estrogen and Estrogen withProgestin Therapies for Postmenopausal Women.”

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Hormone Replacement Therapy –

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Hypogonadism: Types, Causes, & Symptoms –

What Is Hypogonadism?

Hypogonadism occurs when your sex glands produce little or no sex hormones. The sex glands, also calledgonads, are primarily the testes in men and the ovaries in women. Sex hormones help control secondary sex characteristics, such as breast development in women, testicular development in men, and pubic hair growth. Sex hormones also play a role in the menstrual cycle and sperm production.

Hypogonadism may also be known asgonad deficiency. It may be calledlow serum testosteroneorandropause when it happens in males.

Most cases of this disorder respond well to appropriate medical treatment.

9 Warning Signs of Low Testosterone


There two types of hypogonadism are primary and central hypogonadism.

Primary hypogonadism means that you dont have enough sex hormones in your body due to a problem in your gonads. Your gonads are still receiving the message to produce hormones from your brain, but they arent able to produce them.

In central hypogonadism, the problem lies in your brain. The hypothalamus and pituitary gland in your brain, which control your gonads, arent working properly.


The causes of primary hypogonadism include:

Central, or secondary, hypogonadism may be due to:


Symptoms that may affect females include:

Symptoms that may affect males include:


Your doctor will conduct a physical exam to confirm that your sexual development is at the proper level for your age. They may examine your muscle mass, body hair, and your sexual organs.

If your doctor thinks you might have hypogonadism, the first round of testing will involve checking your sex hormone levels. Youll need a blood test to check your level of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Your pituitary gland makes these reproductive hormones.

Youll have your estrogen level tested if youre female. Youll have your testosterone level tested if youre male. These tests are usually drawn in the morning, which is when your hormone levels are highest. If youre male, your doctor may also order a semen analysis to check your sperm count. Hypogonadism can reduce your sperm count.

Your doctor may order more blood tests to help confirm the diagnosis of hypogonadism and rule out any underlying causes.

Iron levels can affect your sex hormones. For this reason, your doctor may test for anemia, or iron deficiency. Your doctor may also wish to measure your prolactin levels. Prolactin is a hormone that promotes breast development and breast milk production in women, but its present in both genders. Your doctor may also check your thyroid hormone levels because thyroid problems can cause symptoms similar to hypogonadism.

Imaging tests can also be useful in diagnosis. Anultrasoundof the ovaries uses sound waves to create an image of the ovaries and check for any problems, including ovarian cysts and polycystic ovarian syndrome (PCOS).Your doctor may order MRIscans or CTscans to check for tumors in your pituitary gland.


Your treatment will involve increasing the amount of female sex hormones in your body if youre a woman.

Your first line of treatment will probably be estrogen therapy if youve had a hysterectomy. Either a patch or pill can administer the supplemental estrogen hormone.

Because increased estrogen levels can increase your risk of endometrial cancer, youll be given a combination of estrogen and progesterone if women who havent had a hysterectomy. Progesterone can lower your risk of endometrial cancer if youre taking estrogen.

Other treatments can target specific symptoms. If youre a woman and you have a decreased sex drive, you may receive low doses of testosterone. If you have menstrual irregularities or trouble conceiving, you may receive injections of the hormone human choriogonadotropin (hCG) or pills containing FSH to trigger ovulation.

Testosterone is a male sex hormone. Testosterone replacement therapy (TRT) is a widely used treatment for hypogonadism in males. You can get testosterone replacement therapy by:

Injections of a gonadotropin-releasing hormone may trigger puberty or increase your sperm production.

Treatment for males and females is similar if the hypogonadism is due to a tumor on the pituitary gland. Treatment may include radiation, medication, or surgery to shrink or remove the tumor.


According to the Urology Care Foundation, hypogonadism is a chronic condition that requires lifelong treatment. Your sex hormone level will probably decrease if you stop treatment.

Seeking support through therapy or support groups can help you before, during, and after treatment.

Can Testosterone Supplements Improve Your Sex Drive?

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Hypogonadism: Types, Causes, & Symptoms –

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DMG Health – About Us

Martin Nwosu MD is the founder and medical director of Doctors Medical Group (DMG) Health and wellness center. Founded in 2010, DMG is the leading Anti-Aging and Functional Medicine specialty practices in Middle Tennessee and surrounding states. The practice reflects his passion to bring an integrative approach to patient care that combines the latest in scientifically validated treatment protocols with the best of conventional medical therapies.

Dr. Nwosu specializes in treating men and women with bio-identical hormone replacement, weight management, a functional approach to treating and preventing chronic disease, and therapies to reverse the symptoms of aging and enhance overall wellness and longevity. Dr. Nwosu is a diplomat in Geriatric medicine, a board-certified internal medicine, a member of the American Academy of Anti-Aging Medicine and a member of the American Association of Pain Management. His practice emphasizes a thorough competency in the areas of nutrition, fitness, stress reduction, bio-identical hormone replacement and spirituality as a necessary basis for optimal health

By utilizing bio-identical hormone products that restore hormones to optimal levels, strengthen the immune system, and increase energy levels, we are able to help you regain and prolong your quality of life. Our Center has many years of experience in treating hypothyroidism, adrenal fatigue and hormone imbalances using bioidentical hormones, desiccated thyroid supplementation and Dr. Nwosus 8-Point Treatment Regimen. Given our years of experience, level of expertise, and renowned treatment using bio-identical hormones, the DMG Health & Wellness Center is considered the Hormone center of choice.

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DMG Health – About Us

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Melatonin – Impressive Health Benefits | Life Extension …

New research indicates that melatonin does much more than help some people sleep better. Exciting studies show that melatonins multifaceted effects may improve treatment outcomes in cancer patients and extend their lives. Additional applications of melatonin include guarding the nervous system against degenerative diseasessuch as Alzheimers disease and strokeand preventing debilitating migraines.

Melatonin is secreted from the pineal gland deep inside the brain. For more than a quarter-century, scientists have been intrigued by melatonins ability to coordinate the bodys physiological rhythms that help set the brains biological clock.

The principal factor affecting melatonin is light, which inhibits the secretion of this hormone. Darkness has the opposite effect from light, resulting in signaling to the pineal gland to increase melatonin secretion. The normal cycles of melatonin production are altered due to factors including aging, medications, and light exposure at night. While the long-term health effects of disrupted melatonin secretion are not yet fully known, some scientists have suggested that years of working nights could lead to adverse effectseven cancer.

Fortunately, melatonin supplements can safely and effectively restore balance to the bodys circadian rhythm of this important hormonehelping achieve a restful nights sleep and keeping your biological clock ticking throughout a long, healthy life span.

Melatonin is a powerful and versatile antioxidant produced within the body. Melatonin protects both lipids and proteins against damage, and can scavenge some of the most dangerous free radicals in the bodyincluding hydroxyl radicals and hydrogen peroxide. Unlike other antioxidants, melatonin easily diffuses into all cells, and even crosses the blood-brain barrier to protect the delicate brain.1

Unfortunately, levels of naturally produced melatonin decline with advancing age, leaving older adults with limited antioxidant protection against conditions associated with oxidative stress, particularly neurodegenerative diseases.1 Supplementing with melatonin may thus help older adults enhance their antioxidant protection against some of the most ravaging diseases of aging, such as Alzheimers disease, Parkinsons disease, and stroke.

Melatonin levels are particularly low in patients with Alzheimers disease. Nearly half of affected individuals suffer from sleep disturbances and sundowningincreased confusion, agitation, and other symptoms in the afternoon and evening.2 Not surprisingly, melatonin supplementation benefits patients with Alzheimers disease by improving sleep and reducing late-day aggravation of symptoms. Melatonin has also been found to decrease cognitive deterioration in individuals with Alzheimers disease, possibly by protecting brain cells from the toxic protein, beta-amyloid.2

Melatonin may likewise play an important role in assisting patients suffering from Parkinsons disease. Parkinsons disease is associated with disrupted melatonin secretion in the brain, and supplemental melatonin may help improve sleep efficiency in affected adults.3

The brain can suffer dramatic, irreparable damage when an individual suffers a stroke. Utilizing animal models of stroke, scientists have found that melatonin may offer important protection against stroke-related damage and deterioration. When administered at the time of stroke, melatonin limited the area of brain tissue damage, decreased brain cell death, lessened behavioral deficits, and reduced the rate of stroke-related death. These investigators believe that melatonins protective actions stem from its free-radical-scavenging and antioxidant activities, and suggest that melatonin may hold promise in improving stroke outcomes in humans.4

Melatonin may help manage one of the leading risk factors for strokeelevated blood pressure. While an earlier study reported that hypertensive men taking melatonin experienced reduced nighttime blood pressure, a newer study confirms the same benefit for women.5 In a randomized, double-blind study, 18 women

(aged 47 to 63) with either normal blood pressure or treated high blood pressure received a three-week course of slow-release melatonin (3 mg) or placebo, one hour before bedtime. Researchers recorded blood pressure readings for 41 hours at the end of the trial. While the daytime blood pressure readings remained unchanged com-pared to placebo, the melatonin treatment significantly decreased nighttime blood pressure, without modifying heart rate.6

One of melatonins most important applications is in fighting a wide array of cancers, including breast and liver cancers, non-small-cell lung cancer, and brain metastases from solid tumors.7

When women with metastatic breast cancer who had failed to respond to tamoxifen received melatonin supplements (20 mg every evening), they demonstrated an improved response to the chemotherapy drug. More than one quarter of the subjectswhose disease otherwise was expected to progress rapidlybegan responding to the chemotherapy treatment. Most of the women also experienced anxiety relief from the melatonin supplementation.8 Laboratory studies suggest that melatonin may help fight hormone-responsive breast cancers by inhibiting the aromatase enzyme, which is responsible for the local synthesis of estrogens.9,10

Emerging research suggests that melatonin may help fight one of the most common malignancies in aging menprostate cancer. In the laboratory, scientists treated androgen-sensitive and androgen-insensitive prostate cancer cells with pharmacological concentrations of melatonin. Treatment with melatonin dramatically reduced the number of prostate cancer cells, while the remaining cells displayed signs of slowed replication and increased differentiationcharacteristics of healthy, non-cancerous cells. Melatonin may thus hold promise against prostate cancers, whether they are hormone-sensitive or hormone-insensitive.11

Scientists conducted a meta-analysis of 10 randomized, controlled trials examining melatonins effects (alone or as an adjuvant treatment) on patients with various types of cancer. Supplementation with melatonin reduced the relative risk of death at one year by an impressive 34%regardless of the type of cancer or the melatonin dosage. Importantly, no adverse effects were reported.12

In addition to its benefits for cancer survival, melatonin may also help counteract the toxicity of chemotherapy treatment. Two-hundred-fifty individuals undergoing chemotherapy for advanced cancers of the lung, breast, gastrointestinal tract, or head and neck received chemotherapy, either alone or in combination with melatonin (20 mg/day). After one year, the melatonin-supplemented individuals demonstrated a higher rate of survival, and were significantly protected against many of the side effects associated with chemotherapy, including decreased platelet count, neurotoxicity, heart damage, mouth sores, and fatigue.13

A promising study suggests that migraine sufferers may be able to reduce the frequency and severity of their headaches by using melatonin. Researchers gave 34 migraine sufferers (29 women and 5 men) a 3-mg dose of melatonin, 30 minutes before bedtime, for three months. Of the 32 patients who finished the study, more than two thirds experienced at least a 50% reduction in number of headaches per month. Additionally, the intensity and duration of headaches decreased. The scientists believe that melatonins anti-inflammatory effect and free-radical-scavenging effects contribute to its headache-relieving benefits.14

Obtaining sufficient amounts of quality sleep is an absolute necessity for good health, yet many of us experience sleep difficulties on occasion. Insomnia occurs due to a variety of factorsranging from long hours of work or travel to sleep-disruptive conditions, such as urinary frequency and stressful events. Elderly adults may be particularly susceptible to difficulty sleeping and nighttime awakenings, due to the decline in melatonin levels associated with aging.15 Melatonin can help promote healthy sleep patterns in some people, regardless of the cause of insomnia.

A large analysis revealed several of melatonins sleep-enhancing benefits. Reviewing 15 studies of sleep in healthy adults, scientists noted that melatonin administration significantly reduced sleep latency (the amount of time needed to fall asleep), while boosting sleep efficiency (the percentage of time in bed spent asleep) and increasing total sleep duration.16

Men with benign prostatic enlargement often experience poor sleep due to nighttime urinary frequency. Scientists from the United Kingdom found that melatonin may offer an effective solution. When 20 older men were treated with 2 mg of melatonin each day for one month, they experienced a significant decrease in nighttime urination, and reported that their condition was less bothersome than before treatment.15

Individuals who work the night shift are often chronically tired due to difficulty falling asleep during the daytime. Supplementing with melatonin has helped improve the length and quality of daytime sleep in these individuals. These findings demonstrate an important characteristic of melatonin: the hormone exerts its hypnotic (sleep-inducing) and sedative (anxiety-relieving) effects, regardless of dosage time.7

Traveling to different time zones often leads to the fatigue and insomnia known as jet lag. Supplementing with melatonin can help prevent or reduce jet lag, particularly when traveling across several time zones. Melatonin works by helping re-synchronize the bodys circadian rhythms, helping the traveler adapt to the local time.7

Melatonin is used in doses ranging from 0.3-5.0 mg to promote sleep, with doses of 1-3 mg most common.17 Studies examining melatonins effects on cancer have utilized doses of 3-50 mg/day.7

Melatonin has a sedating effect, which may be magnified by the use of benzodiazepines or other sedating drugs such as antihistamines or antidepressants. Similarly, the use of melatonin with valerian, 5-hydroxytryptophan, or alcohol may increase sedation.17

The bioavailability of oral melatonin is increased by co-administration of the antidepressant drug fluvoxamine (Luvox).17 Beta blockers, as well as aspirin and other non-steroidal anti-inflammatory drugs, may decrease melatonin production in the body.17

A factor in restorative sleep, melatonins benefits extend to neuroprotection and fighting cancer. Its powerful antioxidant effect offers important enhancements to the brain and nervous system, helping protect against age-related damage. Most exciting are melatonins benefits for cancer patientsrelieving anxiety and improving survival from an array of cancers. Finally, migraine sufferers using melatonin may enjoy a vast decline in the frequency and severity of their headachesleading to a tremendously improved quality of life.

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Melatonin – Impressive Health Benefits | Life Extension …

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CRISPR Update CRISPR Updates, News and Articles

Sharifnia, T., et. al. (2017) Cell Chemical Biology. 24:1075-1091.

Rare cancers have traditionally been difficult to study due to low incidence and limited sample availability. However, new technologies, such as sequencing, have allowed for a greater understanding of the underlying genetic causes. In tandem with sequencing technologies, CRISPR/Cas and small molecule screens have allowed researchers to rapidly screen rare cancers for possible mechanisms and treatments.

Sharon Begley, STAT, 25 September 2017,

The season of Nobel Prize awards has arrived, and with it comes a slew of predictions. This year, STAT has identified who they believe has the best chance of winning the Nobel Prize in Medicine; including the CRISPR crowd of Emmanuelle Charpentier, George Church, Jennifer Doudna, and Feng Zhang. The only problem being each Nobel Prize can only be awarded to three people.

Rachael Lallensack, Nature News, 18 September 2017,

Two new studies in the Proceedings of the National Academy of Sciences (, provide insight into butterfly wing color. The studies identified two genes, WntA is responsible for creation of the coloring pattern and borders, while optix fills the color within the borders. Understanding butterfly coloration could provide insights into adaptations such as mimicry.

Vella, M.R. et. al. (2017) Scientific Reports 7:11038.

CRISPR/Cas gene drives could be used to eliminate vector-borne diseases such as malaria and Lyme disease. However, release of modified organisms is controversial in part due to unforeseen consequences. Developing strategies for gene drive reversal could prove useful if such problems arise. This paper develops models to evaluate the effectiveness of gene drive counter-measures in order to evaluate their potential use.

Bikard, D., Barrangou, R., (2017) Current Opinion in Microbiology, 37:155-160.

Self-targeting bacteria with CRISPR usually proves fatal. This observation could lead to a new type of antimicrobial where the CRISPR/Cas system is introduced to fight infection. This review discusses how CRISPR/Cas could target bacterial infections, as well as how the system may be delivered to the infection site.

David Nield, Science Alert, 9 September 2017,

The Japanese morning glory plant has traditionally had violet flowers, however using CRISPR to disrupt a single gene, scientists have altered the flower color to white. White morning glories can be found; however, it took 850 years for the white version to appear. CRISPR accomplished the task in less than 12 months. This is the first time CRISPR has been used to alter flower color in higher plants.

Liu, X., et. al. (2017) Cell 170:1028-1043.

Many genes are regulated by cis-regulatory elements, though the molecular composition of these elements remains unknown. In a new study published in Cell, Liu et. al. describe a new technique called CAPTURE (CRISPR affinity purification in situ of regulatory elements) that uses a biotin labeled dCas9 to isolate cis regulatory elements in an unbiased fashion, allowing for insights into genome structure and function.

Stanford Medicine News Center, 29 August 2017,

Researchers at Stanford University School of Medicine have created a new online computer game called Eterna where players design RNA molecules that could act as an on/off switch for Cas9. Molecular biologists at Stanford will then create the most promising molecules and test them in living cells. Researchers aim to have 100,000 players contribute 10 solutions each. As the research team tests the molecules in the lab, they will provide information to the players for further refinement.

Julia Franz and Katie Hiler, WUNC Science Friday, 27 August 2017,

Despite the results of Augusts CRISPR edited embryo paper being called into question, its publication has resulted in an increase in the ethics debate. Scientists agree that CRISPR gene editing will continue to improve and society must grapple with the ethical problems. Ira Flatow sits down with the author of the August Nature article and with Kelly Ormond, genetics professor at Stanford University and member of the Stanford Center for Biomedical Ethics, to discuss the results and how to proceed.

Dieter et. al. (2017) BioRxiv, 181255.

On 02 August 2017, a Nature article claimed a major breakthrough in CRISPR genome editing. Researchers from around the world, including the United States, announced that they had successfully corrected viable human embryos heterozygous for the MYBPC3 mutation that results in heart disease, without mosaicism. Recently, the results of this article have been called into question with the publishing of a BioRxiv article. The authors of the new paper identify other possible mechanisms that could have caused the observed results and suggest additional experiments to effectively prove CRISPR gene editing.

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CRISPR Update CRISPR Updates, News and Articles

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About Stem Cells

Stem cells are found in the early embryo, the foetus, amniotic fluid, the placenta and umbilical cord blood. After birth and for the rest of life, stem cells continue to reside in many sites of the body, including skin, hair follicles, bone marrow and blood, brain and spinal cord, the lining of the nose, gut, lung, joint fluid, muscle, fat, and menstrual blood, to name a few.In the growing body, stem cells are responsible for generating new tissues, and once growth is complete, stem cells are responsible for repair and regeneration of damaged and ageing tissues. The question that intrigues medical researchers is whether you can harness the regenerative potential of stem cells and be able to grow new cells for treatments to replace diseased or damaged tissue in the body.

To find out more about how stem cells are used in research and in the development of new treatments download a copy of The Australian Stem Cell Handbook or visit Stem Cell Clinical Trials to find out more about the latest clinical research using stem cells.

Stem cells can be divided into two broad groups:tissue specific stem cells(also known as adult stem cells) andpluripotent stem cells(including embryonic stem cells and iPS cells).

To learn more about the different types of stem cells visit our frequently asked questions page.

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About Stem Cells

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CRISPR breakthrough could drop miscarriage rates | TechCrunch

Gene-editing technology CRISPR has revealed a clue in how human embryos begin to develop, possibly reducing the risk of miscarriage in those crucial first few weeks of pregnancy.

CRISPR Cas9 can modify or snip out genetic defects thought to contribute to miscarriage, but until now it wasnt clear why some embryos continued to form into a fetus and others did not. However,findings, published Wednesday in the journal Nature, hold genetic clues.

British scientists conducting the study found that a certain human genetic marker called OTC4 played an important role in the formation and development in the early stages of embryonic development. The scientists used CRISPR Cas9 to knock out this important gene in days-old human embryos and found that without it, these embryos ceased to attach or grow properly.

The findings could not only help us better understand why some women suffer more miscarriages than others, but it could also potentially greatly increase the rate of successful in vitro fertilization (IVF) procedures.

IVF is sometimes the only way a couple can make a baby using their own genes, but even with technological improvements over the years, the rates of success are still poor.Only about 36 percent of IVF cycles result in a viable pregnancy, and a mere 24 percent produce a baby, according to the Centers for Disease Control.

Of course, this is not the first time scientists have tested on human embryos. The practice has sparked a fierce international debate, but earlier this year, U.S. scientists used CRISPR technology to cut out a gene known to cause heart defects in three-day old human embryos.

None of the embryos in that study or this latest one were meant to go on to become human beings and were discarded after the study was finished. However, both studies hint at the potential CRISPR could have in the formation of human life in the future.

It will likely take years before putting this breakthrough into practice on viable embryos meant to develop beyond a few days, and theres likely still much more research needed, but it does give hope for those whove suffered a miscarriage and wanting to ensure they can one day carry a healthy baby to full term.

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CRISPR breakthrough could drop miscarriage rates | TechCrunch

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CRISPR gene-editing could result in more successful birth rates

Usually, this type of study is conducted on mice, which are easier to come by and carry less ethical considerations. But, in this case, scientists knocked out the gene in 41 human embryos donated by couples who had undergone in-vitro fertilization (IVF). The researchers claim the switch allowed them to highlight key differences between the role of OCT4 in human and mouse models. The team are hoping their findings can help scientists better grasp why some women suffer more miscarriages than others. Additionally, the study could also increase the rate of successful IVF procedures.

This isn’t the first time scientists have used human embryos. Earlier this year, a team of researchers from Oregon became the first to use CRISPR tech to cut out genes that cause inherited diseases in humans. Before that, scientists in China utilized the technique to repair a gene that can bring about a fatal blood disorder.

The new study is being hailed as a compelling first step. “We were surprised to see just how crucial this gene is for human embryo development, but we need to continue our work to confirm its role,” Norah Fogarty of the Francis Crick Institute told CNN. “Other research methods, including studies in mice, suggested a later and more focused role for OCT4, so our results highlight the need for human embryo research.”

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CRISPR gene-editing could result in more successful birth rates

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Clinic North Vancouver | Bioidentical Hormone Treatments

Our goal is to help you to improve your health and quality of life, while identifying the possible cause of your symptoms. We strive to offer you the best care possible in a professional, spa-like space and support you through the latest Naturopathic Medical practices.

Are you suffering for a health condition you need help treating? Are you generally healthy but have noticed increasing difficulty with your weight, mood, energy, focus or hormones? Thepractitioners at Marine Drive Naturopathic Clinic offer programs and treatments to help you not only to feel better, but examine the cause of your symptoms or conditions.

Our team includes Naturopathic Physicians Dr. Cathryn Coe,Dr. Cameron McIntyre, Dr. Elizabeth Miller, Dr. Lynn Klassen, and Dr. Sarah Wulkan.

Weight gain? Hot flashes? Poor sleep? We offer comprehensive thyroid and hormone testing to identify hormonal imbalances, correcting them using bioidentical hormone treatments or herbal support

Are you or your child affected by learning difficulties or cognitive problems? We offer testing and treatment for conditions such as autism spectrum disorders, Alzheimers disease and dementia, and ADD/ADHD. Our Clinical Counsellor also offers support forparents of children with autism and spectrum disorders

The clinic is conveniently located along Marine Drive in North Vancouver with plenty of free parking and direct access to public transit. Come in, relax, enjoy a cup of tea and read a magazine in our spa-like environment. At Marine Drive Naturopathic Clinic, your treatment begins the minute you walk in the door

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Clinic North Vancouver | Bioidentical Hormone Treatments

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What Is a Hormone Doctor? | Career Trend

A hormone doctor, or an endocrinologist, is a physician who treats diseases related to the endocrine system. While primary care physicians (family practitioners and internal medicine physicians) can treat many hormonal disorders without a need for specialized training, a physician may also receive advanced training and specialize in endocrinology. A primary care physician can determine whether he or she can treat a patient or whether the patient should be referred to a specialist treating only disorders of the endocrine system.

The endocrine system is composed of many glands, including the pituitary, thyroid, parathyroids, adrenals, hypothalamus, pineal body, ovaries and testicles. The islet cells of the pancreas are also part of the endocrine system. These glands secrete hormones (chemical messengers) that regulate the bodys metabolism, growth, sexual development and sexual function, by complex feedback systems comparable to a thermostat regulating room temperature.

A hormone doctor can specialize in diseases of one or two glands or treat patients in all areas of endocrinology. A large part of a typical practice could involve treating diabetes and related complications. The physician may also treat thyroid disorders, inborn metabolic disorders, over- and underproduction of hormones, osteoporosis, menopause, cholesterol disorders, hypertension, and short or tall stature. Patients with endocrine cancer are usually referred to an oncologist.

To treat non-reproductive hormonal disorders, a physician generally completes four years of medical or osteopath school and a three-year residency in either family medicine or internal medicine. He or she must pass a board examination to become board certified in family or internal medicine. To become board certified as an endocrine specialist, the physician completes a three-year endocrinology fellowship program and passes a board certification examination.

Reproductive endocrinologists complete four years of residency training in obstetrics and gynecology, rather than training in family medicine or internal medicine. They must complete two or three years of fellowship training in reproductive endocrinology and infertility and pass the board certification examination. These specialists treat infertility by using in vitro fertilization, embryo and sperm freezing, assisted embryo hatching, pre-implantation genetic diagnosis and other emerging technologies. Reproductive endocrinologists also treat a wide range of reproductive disorders, including endometriosis, polycystic ovary syndrome, gonadal dysgenesis, galactorrhea, repeat pregnancy loss, ectopic pregnancy and excess hair in women, to name just a few.

A hormone doctor may work in academic medical centers, community hospitals, private group practices or private solo practices. Each situation can involve different work hours, a different patient base, and different lifestyles. Unlike surgical specialties, hormone doctors generally do not take call hours, but they may be called on an emergency basis to see a patient in a hospital when the physician on staff cannot appropriately treat the patient.

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What Is a Hormone Doctor? | Career Trend

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Gene therapy | Cancer in general | Cancer Research UK

Gene therapy is a type ofbiological therapy for cancer that is still in the early stages of research.

Genes are coded messages that tell cells how to make proteins. Proteins are the molecules that control the way cells behave. Our genes decide what we look like and how our body works.We have many thousands of separate genes.

Genes are made ofDNAand they are in the nucleus of the cell. The nucleus is the cell’s control centre.Genes are grouped together to make chromosomes. We inherit half our chromosomes from our mother and half from our father.

Cancer cells are different from normal cells. They have changes (called faults or mutations) in several of their genes which make them divide too often and form a tumour. The genes that are damaged mightbe:

Many gene changes that may make a cell become cancerous are caused by environmental or lifestyle factors, such as smoking.

Some people have inherited faulty genes that increase their risk of particular types of cancer. Inherited damaged genes cause between 2 and 3 in every 100 (2% to 3%) of cancers.

Gene therapy is a type of treatment which uses genes to treat illnesses. Researchers have been developing differenttypes of gene therapyto treat cancer.

The ideas for these new treatments have come about because we are beginning to understand how cancer cells are different from normal cells. It is stillearly days for this type of treatment. Some of these treatments are being looked at in clinical trials. Otherscan now be used for some people with types of cancer such as melanoma skin cancer.

Getting genes into cancer cells is one of the most difficult aspects of gene therapy. Researchers are working on finding new and better ways of doing this. The gene is usually taken into the cancer cell by a carrier called a vector.

The most common types of carrier used in gene therapy are viruses because they can enter cells and deliver genetic material. The viruses have been changed so that they cannot cause serious disease but they may still cause mild, flu like symptoms.

Some viruses have been changed in the laboratory so that they target cancer cells and not healthy cells. So they only carry the gene into cancer cells.

Researchers are testing other types of carrier such as inactivated bacteria.

Researchers are looking at different ways of using gene therapy:

Some types of gene therapy aim to boost the body’s natural ability to attack cancer cells. Ourimmune systemhas cells that recognise and kill harmful things that can cause disease, such as cancer cells.

There are many different types of immune cell. Some of them produce proteins that encourage other immune cells to destroy cancer cells. Some types of therapy add genes to a patient’s immune cells. Thismakes them better at finding or destroying particular types of cancer.

There are a few trials using this type of gene therapy in the UK.

Some gene therapies put genes into cancer cells to make the cells more sensitive to particular treatments. The aim is to make treatments,such as chemotherapy or radiotherapy, work better.

Some types of gene therapy deliver genes into the cancer cells that allow the cells to change drugs from an inactive form to an active form. The inactive form of the drug is called a pro drug.

First of all you have treatment with the the carrier containing the gene, then you havethe pro drug.The pro drug circulates in the body and doesn’t harm normal cells. But when it reaches the cancer cells, it is activated by the gene and the drug kills the cancer cells.

Some gene therapies block processes that cancer cells use to survive. For example, most cells in the body are programmed to die if their DNA is damaged beyond repair. This is called programmed cell death or apoptosis. Cancer cells block this process so they don’t die even when they are supposed to.

Some gene therapy strategies aim to reverse this blockage. Doctors hope these new types of treatment will make the cancer cells die.

Some viruses infect and kill cells. Researchers are working on ways to change these viruses so they only target and kill cancer cells, leaving healthy cells alone.

This sort of treatment uses the viruses to kill cancer cells directly rather than to deliver genes. So it is not cancer gene therapy in the true sense of the word. But doctors sometimes refer to it as gene therapy.

A drug called T-VEC (talimogene laherparepvec)isnowavailable as a treatmentfor melanoma skin cancer. It isalso calledImlygic. It is also being looked at in trials for other types of cancer, such as head and neck cancer.

T-VEC uses a strain of the cold sore virus (herpes simplex virus)that been changed by altering the genes that tell the virus how to behave. It tells the virus to destroy the cancer cells and ignore the healthy cells.

T-VEC can beused to treatsome people with melanoma skin cancer whose cancer cannot be removed with surgery. You have T-VEC as an injectiondirectly into yourmelanoma.

Use the tabs along the top to look at recruiting,closed and results.

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Gene therapy | Cancer in general | Cancer Research UK

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Relief of Overactive Bladder – page 1 | Life Extension …

A common and frustrating complaint we at Life Extension hear is how to stop urinary incontinence.

Our frustration has been that despite aggressive research, we could not identify a safe solution to this problem that plagues so many aging women (and men to a lesser extent).

Even more numerous are inquiries we receive from people seeking relief from frequent daytime and nighttime urinary urges.

In a breakthrough discovered by Japanese scientists, a natural plant extract combination has been shown to reduce incontinent episodes by up to 79%,1 daytime urination by up to 39%,2 and nighttime urination by up to 68%.3

This article will discuss the research findings on maturing women who found significant relief after taking this novel supplement for only six to eight weeks.

Additionally, this article will discuss more limited data obtained when men suffering from nighttime urinary urgencies were given this same plant extract.

Urinary frequency becomes more common with advancing age, with nearly half of people over 60 reporting to suffer from nocturia (two or more episodes of urination during the night).

Urinary incontinence is defined as an involuntary loss of urine. It represents a major social and hygiene problem in the aging population. About 48% of women and 17% of men over age 70 suffer urinary incontinence.4

Overactive bladder affects one in six adults over age 40, and is defined as having an urgent need to empty the bladder during the day-night, along with incontinence. Those afflicted with an overactive bladder have to go to the bathroom frequently, leak urine into their clothes, and report feeling depressed, stressed, and sleep-deprived.

In women, stress incontinence (involuntary loss of urine during physical activity such as sneezing or exercise) is usually caused by a weakening of the bladder sphincter and pelvic floor muscles. Shrinkage (atrophy) of tissues where the bladder and urethra meet also contributes to the problem. Hormonal changes occurring after menopause are thought to be an underlying cause of these anatomical changes in the bladder sphincter that lead to urinary incontinence.

In postmenopausal women, decreased androgen (testosterone) levels weaken the pelvic floor and sphincter muscles, while an estrogen deficit induces atrophy of the urethra.

Mainstream medicine offers only mediocre therapies to address urinary incontinence. Drugs commonly used for this condition are expensive and side-effect-prone. Only a small proportion of the affected population seeks treatment because most people consider their urinary symptoms a consequence of normal aging.

Fortunately, a safe, natural, and low-cost approach has been developed that has demonstrated remarkable benefits in human clinical trials.

Pumpkin seeds were traditionally used by Native American tribes to facilitate passage of urine. A European herbal encyclopedia first mentioned the use of pumpkins seeds to treat urinary problems in the year 1578. The German health regulators approve pumpkin seed as a treatment for irritable bladder.

Pumpkin seed oil has been included in products used to alleviate urinary difficulties. While some effects have been shown when using the fat-soluble (oil) fraction of the pumpkin seed, it is the water-soluble portion that demonstrated impressive symptomatic effects in recent studies.

Japanese scientists have patented a method to obtain the water-soluble constituents of the pumpkin seed, which are absorbed far more efficiently into the bloodstream.

Urinary incontinence worsens after menopause. While menopausal problems are usually associated with estrogen deficit, low levels of testosterone and progesterone are also underlying culprits.

Water-soluble pumpkin seed extract exerts an anabolic (tissue-building) effect on the pelvic floor muscles via several mechanisms. By inhibiting the aromatase enzyme, it may make more testosterone available to strengthen the pelvic muscles.5

Secondly, this water-soluble pumpkin seed fraction binds to the androgen receptor on pelvic muscle cells, thus inducing a strengthening effect. This is important because androgen receptors are expressed in the pelvic floor and lower urinary tract in humans.6 By promoting androgenic activity, water-soluble pumpkin seed extract may play an important role in female pelvic floor structural integrity and lower urinary tract disorders.5

Nitric oxide is a molecule critically involved in lower urinary tract functions. For the urination muscles to relax when the bladder is full, nitric oxide is required. When nitric oxide synthesis is inhibited, the result is bladder hyperactivity and reduced bladder volume.

The dual mechanisms of strengthening pelvic floor muscles, while increasing nitric oxide synthesis,5 help explain how water-soluble pumpkin seed extract alleviated urinary incontinence in three separate studies on aging women.1-3

Soy extracts provide standardized phyoestrogens that are potentially effective in ameliorating geriatric symptoms relating to estrogen deficit.

The ingestion of standardized soy extract has been hypothesized to decrease the atrophy of tissues where the bladder and urethra meet and thus alleviate frequent urinary urges and incontinence.

A study was done to evaluate the effects of water-soluble pumpkin seed extract in anesthetized rats to determine bladder functionality.7

As measured by a cystometrogram, bladder parameters showed a dramatic 54.5% improvement in rats receiving water-soluble pumpkin extract compared to other agents.

When the excretion frequency was measured, a 60% reduction in urine excretion frequency occurred after administration of water-soluble pumpkin seed extract. No improvement was seen in the group given inactive solvent.

Conclusions from the study showed that water-soluble pumpkin extract significantly increases maximum bladder capacity while decreasing urination frequency.

A study of 39 incontinent females (aged 55-79 years) using water-soluble pumpkin seed and soy isoflavone extracts was conducted over a six-week period.1 The objective was to evaluate the effects on frequency of daytime and nighttime urinations and number of incontinent episodes.

After six weeks, the number of nighttime urinations was reduced from 3.3 to 2.0 a 39% improvement. Daytime urinations went from 8.0 to 6.7 after six weeks a modest 16% improvement.

The number of incontinent episodes, however, plunged to a remarkably low number. Prior to receiving the water-soluble pumpkin seed-soy extract, these women experienced an average of 7.3 incontinent episodes a day. After six weeks of using this supplement, daily incontinent episodes averaged only 1.5 an astounding 79% decrease in urinary incontinence!

When these women were questioned about the effects they noticed in response to taking water-soluble pumpkin seed-soy extract, there was a 73% subjective improvement in the highest fulfilled category. When the global improvement ratio was evaluated, which included degree of satisfaction after sleeping, 81.8% of women with two to four episodes of nightly urinations reported that they were markedly improved.

A study of 50 incontinent women (aged 35-84 years) was conducted using the same water-soluble pumpkin seed-soy extract supplement to evaluate the effect on stress incontinence episodes.3

Before the pumpkin seed-soy supplement was given, these women averaged 2.1 incontinent events each day. After taking the supplement for six weeks, incontinent events fell to an average of only 0.7 a day a remarkable 67% decrease in stress-induced incontinent episodes!

A consumer test of 10 women (aged 45-65 years) was conducted using the same water-soluble pumpkin seed and soy extract supplement.2

After eight weeks, daytime urinations went from 9.3 to 5.6 a 39% reduction. Nighttime urinations went from 2.0 to 0.8 a 60% reduction.

Prior to initiating the pumpkin seed-soy supplement, there was an average of 2.3 incontinent episodes each day. After eight weeks, the frequency of incontinent episodes declined to only 1.0 per day a 57% reduction!

Relief of Overactive Bladder – page 1 | Life Extension …

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CRISPR: A game-changing genetic engineering technique …

Have you heard? A revolution has seized the scientific community. Within only a few years, research labs worldwide have adopted a new technology that facilitates making specific changes in the DNA of humans, other animals, and plants. Compared to previous techniques for modifying DNA, this new approach is much faster and easier. This technology is referred to as CRISPR, and it has changed not only the way basic research is conducted, but also the way we can now think about treating diseases [1,2].

CRISPR is an acronym for Clustered Regularly Interspaced Short Palindromic Repeat. This name refers to the unique organization of short, partially palindromic repeated DNA sequences found in the genomes of bacteria and other microorganisms. While seemingly innocuous, CRISPR sequences are a crucial component of the immune systems [3] of these simple life forms. The immune system is responsible for protecting an organisms health and well-being. Just like us, bacterial cells can be invaded by viruses, which are small, infectious agents. If a viral infection threatens a bacterial cell, the CRISPR immune system can thwart the attack by destroying the genome of the invading virus [4]. The genome of the virus includes genetic material that is necessary for the virus to continue replicating. Thus, by destroying the viral genome, the CRISPR immune system protects bacteria from ongoing viral infection.

Figure 1 ~ The steps of CRISPR-mediated immunity. CRISPRs are regions in the bacterial genome that help defend against invading viruses. These regions are composed of short DNA repeats (black diamonds) and spacers (colored boxes). When a previously unseen virus infects a bacterium, a new spacer derived from the virus is incorporated amongst existing spacers. The CRISPR sequence is transcribed and processed to generate short CRISPR RNA molecules. The CRISPR RNA associates with and guides bacterial molecular machinery to a matching target sequence in the invading virus. The molecular machinery cuts up and destroys the invading viral genome. Figure adapted from Molecular Cell 54, April 24, 2014 [5].

Interspersed between the short DNA repeats of bacterial CRISPRs are similarly short variable sequences called spacers (FIGURE 1). These spacers are derived from DNA of viruses that have previously attacked the host bacterium [3]. Hence, spacers serve as a genetic memory of previous infections. If another infection by the same virus should occur, the CRISPR defense system will cut up any viral DNA sequence matching the spacer sequence and thus protect the bacterium from viral attack. If a previously unseen virus attacks, a new spacer is made and added to the chain of spacers and repeats.

The CRISPR immune system works to protect bacteria from repeated viral attack via three basic steps [5]:

Step 1) Adaptation DNA from an invading virus is processed into short segments that are inserted into the CRISPR sequence as new spacers.

Step 2) Production of CRISPR RNA CRISPR repeats and spacers in the bacterial DNA undergo transcription, the process of copying DNA into RNA (ribonucleic acid). Unlike the double-chain helix structure of DNA, the resulting RNA is a single-chain molecule. This RNA chain is cut into short pieces called CRISPR RNAs.

Step 3) Targeting CRISPR RNAs guide bacterial molecular machinery to destroy the viral material. Because CRISPR RNA sequences are copied from the viral DNA sequences acquired during adaptation, they are exact matches to the viral genome and thus serve as excellent guides.

The specificity of CRISPR-based immunity in recognizing and destroying invading viruses is not just useful for bacteria. Creative applications of this primitive yet elegant defense system have emerged in disciplines as diverse as industry, basic research, and medicine.

In Industry

The inherent functions of the CRISPR system are advantageous for industrial processes that utilize bacterial cultures. CRISPR-based immunity can be employed to make these cultures more resistant to viral attack, which would otherwise impede productivity. In fact, the original discovery of CRISPR immunity came from researchers at Danisco, a company in the food production industry [2,3]. Danisco scientists were studying a bacterium called Streptococcus thermophilus, which is used to make yogurts and cheeses. Certain viruses can infect this bacterium and damage the quality or quantity of the food. It was discovered that CRISPR sequences equipped S. thermophilus with immunity against such viral attack. Expanding beyond S. thermophilus to other useful bacteria, manufacturers can apply the same principles to improve culture sustainability and lifespan.

In the Lab

Beyond applications encompassing bacterial immune defenses, scientists have learned how to harness CRISPR technology in the lab [6] to make precise changes in the genes of organisms as diverse as fruit flies, fish, mice, plants and even human cells. Genes are defined by their specific sequences, which provide instructions on how to build and maintain an organisms cells. A change in the sequence of even one gene can significantly affect the biology of the cell and in turn may affect the health of an organism. CRISPR techniques allow scientists to modify specific genes while sparing all others, thus clarifying the association between a given gene and its consequence to the organism.

Rather than relying on bacteria to generate CRISPR RNAs, scientists first design and synthesize short RNA molecules that match a specific DNA sequencefor example, in a human cell. Then, like in the targeting step of the bacterial system, this guide RNA shuttles molecular machinery to the intended DNA target. Once localized to the DNA region of interest, the molecular machinery can silence a gene or even change the sequence of a gene (Figure 2)! This type of gene editing can be likened to editing a sentence with a word processor to delete words or correct spelling mistakes. One important application of such technology is to facilitate making animal models with precise genetic changes to study the progress and treatment of human diseases.

Figure 2 ~ Gene silencing and editing with CRISPR. Guide RNA designed to match the DNA region of interest directs molecular machinery to cut both strands of the targeted DNA. During gene silencing, the cell attempts to repair the broken DNA, but often does so with errors that disrupt the geneeffectively silencing it. For gene editing, a repair template with a specified change in sequence is added to the cell and incorporated into the DNA during the repair process. The targeted DNA is now altered to carry this new sequence.

In Medicine

With early successes in the lab, many are looking toward medical applications of CRISPR technology. One application is for the treatment of genetic diseases. The first evidence that CRISPR can be used to correct a mutant gene and reverse disease symptoms in a living animal was published earlier this year [7]. By replacing the mutant form of a gene with its correct sequence in adult mice, researchers demonstrated a cure for a rare liver disorder that could be achieved with a single treatment. In addition to treating heritable diseases, CRISPR can be used in the realm of infectious diseases, possibly providing a way to make more specific antibiotics that target only disease-causing bacterial strains while sparing beneficial bacteria [8]. A recent SITN Waves article discusses how this technique was also used to make white blood cells resistant to HIV infection [9].

Of course, any new technology takes some time to understand and perfect. It will be important to verify that a particular guide RNA is specific for its target gene, so that the CRISPR system does not mistakenly attack other genes. It will also be important to find a way to deliver CRISPR therapies into the body before they can become widely used in medicine. Although a lot remains to be discovered, there is no doubt that CRISPR has become a valuable tool in research. In fact, there is enough excitement in the field to warrant the launch of several Biotech start-ups that hope to use CRISPR-inspired technology to treat human diseases [8].

Ekaterina Pak is a Ph.D. student in the Biological and Biomedical Sciences program at Harvard Medical School.

1. Palca, J. A CRISPR way to fix faulty genes. (26 June 2014) NPR [29 June 2014]

2. Pennisi, E. The CRISPR Craze. (2013) Science, 341 (6148): 833-836.

3. Barrangou, R., Fremaux, C., Deveau, H., Richards, M., Boyaval, P., Moineau, S., Romero, D.A., and Horvath, P. (2007). CRISPR provides acquired resistance against viruses in prokaryotes. Science 315, 17091712.

4. Brouns, S.J., Jore, M.M., Lundgren, M., Westra, E.R., Slijkhuis, R.J., Snijders, A.P., Dickman, M.J., Makarova, K.S., Koonin, E.V., and van der Oost, J. (2008). Small CRISPR RNAs guide antiviral defense in prokaryotes. Science 321, 960964.

5. Barrangou, R. and Marraffini, L. CRISPR-Cas Systems: Prokaryotes Upgrade to Adaptive Immunity (2014). Molecular Cell 54, 234-244.

6. Jinkek, M. et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. (2012) 337(6096):816-21.

7. CRISPR reverses disease symptoms in living animals for first time. (31 March 2014). Genetic Engineering and Biotechnology News. [27 July 2014]

8. Pollack, A. A powerful new way to edit DNA. (3 March 2014). NYTimes [16 July 2014]

9. Gene editing technique allows for HIV resistance? [13 June 2014]

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CRISPR: A game-changing genetic engineering technique …

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Thanks to CRISPR, gene-edited pigs could be organ donors for …

Why it matters to you

Pigs could be a solution to the shortage of transplant organs. CRISPR gene editing makes them safer candidates.

There is a massive shortage of transplant organs worldwide, and scientists are desperate to come up with a solution whether that be boosting patients immune systems to let them accept otherwise incompatible organs, or creating technology for preserving organs after they are harvested. A new international research initiative has another approach: Using CRISPR gene editing on pigs to make them into safe organ donor candidates for humans.

The reason pigs are desirable as possible sources of organs is that their organs are similar to humans in both size and anatomy. Unfortunately, they also carry viruses known as porcine endogenous retroviruses (PERVs) embedded in their DNA. As this research demonstrated, this can be passed on to humans, although gene editing can be used to eradicate it.

Currently, the major problem of human transplants is the great shortage of transplantable human organs, Lin Lin, a researcher in the department of biomedicine at Denmarks Aarhus University, told Digital Trends. While using pig organs, we can in principle use as many as we need. Eradicating PERVs makes porcine organs safer for human transplants. However, there are still several other barriers that we have to cross in order to make pig organs better for human transplants. This is now achievable with the great development in CRISPR gene editing.

Using an optimized CRISPR-Cas9 gene editing technology and porcine somatic cell nuclear transfer, this work successfully generated viable pigs that are 100 percent PERV-inactivated.Thirty-seven PERV-inactive piglets have so far been born, with 15 remaining alive. The oldest of these is four months old, which means it will need to be monitored for a longer period of time to make sure it suffers no ill-effects.

The next major step is to solve the problem of vigorous immune responses, such as complement activation, coagulation and thrombosis, triggered by xenotransplantation, Lin said. Many previous works have demonstrated that the immunological incapability can be alleviated through tailoring the pig genome. Thus, a serial of very sophisticated gene editing and modifications will be further introduced into the PERV-inactivated pigs and tested in higher primates.

A paper describing the research was recently published in the journal Science.

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Thanks to CRISPR, gene-edited pigs could be organ donors for …

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CRISPR – CRISPR-Cas9 | Gene Editing

CRISPR or CRISPR Cas9 is commonly used to refer to a revolutionary genome editing technology that enables efficient and precise genomic modifications in a wide variety of organisms and tissues.

Definition: Clustered Regularly Interspaced Short Palindromic Repeat or CRISPR (pronounced ‘crisper’) was identified in a prokaryotic defence system. CRISPR are sections of genetic code containing short repetitions of base sequences followed by spacer DNA segments

Identified in archaea and bacteria, short nucleic acid sequences are captured from invading pathogens and integrated in the CRISPR loci amidst the repeats. Small RNAs, produced by transcription of these loci, can then guide a set of endonucleases to cleave the genomes of future invading pathogens, thereby disabling their attacks.

Definition: CRISPR ASsociated protein 9 (Cas 9) is an endonuclease used in an RNA-guided gene editing platform. It uses a synthetic guide RNA to introduce a double strand break at a specific location within a strand of DNA

Cas9 was the first of several restriction nucleases (or molecular scissors) discovered that enable CRISPR genome editing. The CRISPR Cas9 mechanism has since been adapted into a powerful tool that puts genome editing into the mainstream.

In the laboratory, CRISPR Cas9 genome editing is achieved by transfecting a cell with the Cas9 protein along with a specially designed guide RNA (gRNA) that directs the cut through hybridization with its matching genomic sequence. When the cell repairs that break, errors can occur to generate a gene knockout or additional genetic modifications can be introduced. Our CRISPR gene editing technology is particularly good for the efficient generation of complete knockout of genes on multiple alleles.

Use of wild-type Cas 9 has been shown to lead to off-target cleavage, but a modified version introduces only single strand nicks to the DNA, which in pairs still stimulate the repair mechanisms while significantly decreasing the risk of off-target cutting.

Horizon has licensed gene editing IP from Harvard University, the Broad Institute and ERS Genomics with the goal of being able to ensure that we will be able to offer uninterrupted use of CRISPR tools to our customers. Our scientists have extensive knowledge of CRISPR technology including the benefits of using each Cas9 structure.

Other Gene Editing Systems

Genome editing can be achieved using the widely used S. Pyogenes (spCas9), and also utilising CRISPR Cas 9 protocol for S. Aureus (scCas9), Cpf1, HiFi Cas9, Nickase Cas9, Nuclease Cas9, NgAgo gDNA and even synthetic spCas9 with alternative PAM sites.

Our genome editing knowledge also includes rAAV and ZFNs.

Continue your CRIPSR/Cas9 research with ourpopular education and training webinars:

Find out more about our exciting upcoming eventwhere the future of CRISPR will be discussed:

The CRISPR Forum 2017

Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P, Moineau S, Romero DA, Horvath P. 2007.CRISPR provides acquired resistance against viruses in prokaryotes. Science 315(5819): 1709-1712.

Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. 2012.A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337(6096): 816-821.

Continued here:
CRISPR – CRISPR-Cas9 | Gene Editing

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Birth of CRISPR’d pigs advances hopes for turning pigs into …


ioengineer Luhan Yang swiped through the photos on her phone until she got to one that made her beam: It showed her crouching down by a pudgy, wide-eyed newborn she calls my baby.

This newborn is a pig, and its the first to be born with dozens of genetic changes that could enable scientists to turn swine into a source of organs for human transplants, Yang and her colleaguesreported on Thursday in Science.

Theynamed the piglet Laika, after the first dog to orbit Earth in 1957. The new Laika, born this year in China after numerous miscarriages and other setbacks, could be a pioneer in her own right. Using the genome-editing technology CRISPR-Cas9, Yang and her team at the biotech startup eGenesis knocked out pig DNA that has long been considered a deal-breaker for efforts to use pigs as organ donors. Laika and 36 other designer piglets are completely free of it.


There are additional Olympic-level hurdles to overcome before people facing death from organ failure get replacement kidneys, hearts, livers, or lungs from the species that provides their bacon and pork chops.Other genetic changes will be necessary. And regulators require stringent tests in lab primates before a single patient could get a CRISPRd pig organ; that will take years.

But after decades of dashed hopes, experts say, xenotransplantation might actually be in the offing.

Its an elegant tour de force of genetic engineering, so my hat is off to them, said Dr. A. Joseph Tector, of the University of Alabama, Birmingham, who has also made genetically modified pigs aimed at producing transplantable organs. But if you want to move xenotransplantation to the hospital, there are many more things youll have to do.

Doctors wont have to do much persuasion, however, to get patients to accept organs from another species. There is so much desperation among people on transplant lists, and 20 a day are dying as they wait, said Dr. Adam Griesemer, a xenotransplantation researcher and transplant surgeon at Columbia University Medical Center. This could be a path to a transplant for them. Colleagues keep asking me when were going to do it.

Pigs are scientists first choice because their organs and physiology are pretty close matches to humans, and they come with less ethical baggage than, say, chimps or baboons. But for years, the path to xenotransplantation has been paved with disappointment. Pig organs with genetic changes, transplanted into baboons and other lab animals,kept failing within weeks, even though the recipients received immune-suppressing drugs to prevent organ rejection.

Yang believes that CRISPR can accomplish what previous approaches have not: make multiple, simultaneous changes in pig DNA so that the animals organs work, and work safely, in people.

The team at Massachusetts-based eGenesis, working with scientists in China, used the Dolly recipe to clone pigs. They started with cells from adult pigs, and used an electrical jolt to fuse them with pig ova whose DNA had been removed. They grew the resulting embryos in lab dishes and then transferred healthy ones to sows, hoping for pregnancies.

The adult cells were not as nature made them, however. In a key step, the scientists used the genome-editor CRISPR to cripple all 25 copies of PERV genes DNA in the pig genome that makes potentially dangerous viruses that could infect anyone who receives a pig organ. (PERV stands for porcine endogenous retroviruses.) Initially, in about one-third of the CRISPRd pig cells, the PERV genes were almost all gone. In most of the rest, CRISPR missed its mark. That wasnt unexpected; for all the hype around CRISPR, it isnt perfect.

The unwelcome surprise was that cells that were effectively CRISPRd the ones the scientists needed to clone designer pigs were dying like orchids in the tundra. Apparently, in its zeal to attack so many PERV genes, CRISPR had shredded the cells genomes fatally.

Its quite a problem, when you move to so many targets, said Yang, the chief scientific officer at eGenesis. If there are multiple cuts in the genome at the same time, chromosomes rearrange themselves. That can happen when you make two or three [CRISPR edits], and were dealing with 25.

The eGenesis scientists, many of them alums of George Churchs lab at Harvard Medical School, scrambled for a solution. They eventually stumbled on a cocktail of molecules that both increased the number of PERV targets that CRISPR hit and, even better, kept the well-CRISPRd cells alive. We were able to get cells to grow even with very aggressive gene editing, Yang said: 100 percent of the cells doused with the chemical cocktail were 100 percent PERV-free.

As is typical with cloning, very few of the cloned embryos were healthy enough to implant into sows, and few implanted embryos resulted in births. Crucially, however, of the 37 piglets born from 17 sows, all were PERV-free. And CRISPR did not change any DNA it wasnt supposed to; there were no off-target effects.

The oldest pigs are nearly 5 months old, or adolescents; 15 remain alive. The rest were killed so the scientists could see whether their organs were developing normally.

So far, so good, Yang said, showing that pigs dont need PERVs to live: Weve shown you can produce PERV-free pigs which could serve as a source for future xenotransplants.

Among eGenesiss next experiments: see if the pigs are fertile and, if so, whether their CRISPRd genetic changes, including inactivating PERVs, are inherited. That could provide an easier source of transplantable organs than cloning.

Other scientists have also used CRISPR to produce pigs with altered genomes, including pigs in which a genethat triggers organ rejection was eliminated. Last year, scientists announcedthat hearts from genetically-modified pigs survived in baboons for up to 945 days, a record.

UABs Tector and his colleagues, with financial backing from United Therapeutics Corp., are using CRISPR not on PERVs but on other pig genes. Knocking out threein particular could protect pig organs from being attacked by the human immune system, he said; lab macaques that received kidneys from the pigs have survived as long as 499 days. We have a pig we are very confident we can make work for kidney transplants, Tector said.

There is disagreement about whether pig organs would have to be PERV-free to be successfully transplanted into people. Tector said transplant patients could take anti-retroviral drugs, just as they take immune-suppressing drugs, to kill the viruses.

Nevertheless, eGenesis scientists achievement with their 25 DNA edits, the eGenesis pigs set the record for genome modifications suggests that however many edits are needed to make pigs into organ donors might be feasible. The challenge is to identify which pig genes are necessary and sufficient to change so that the animals organs have a shot at working in people.

Senior Writer, Science and Discovery

Sharon covers science and discovery.

Birth of CRISPR’d pigs advances hopes for turning pigs into …

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