Page 3«..2345..1020..»

Archive for the ‘Gene Therapy Research’ Category

Birth control research is moving beyond the pill – Science News Magazine

Mention the pill, and only one kind of drug comes to mind. The claim that oral contraceptives have on that simple noun testifies to the pills singular effect in the United States. Introduced in 1960, the pill gave women reliable access to birth control for the first time. The opportunity to delay having children opened the door to higher education and professional careers for many women.

More than 50 years later, the most commonly used form of reversible contraception in this country is still the pill. Additional methods have been developed for women such as implants, patches, vaginal rings and injectables but most do basically the same thing as the pill: use synthetic versions of sex steroid hormones to suppress ovulation. The method has proved its merit, but the current crop of contraceptives doesnt work for everyone. Some women cant tolerate the side effects stemming from manipulation of the hormones. Others cant use hormonal contraceptives at all, because of underlying health conditions.

In a survey, 62 percent of U.S. women ages 15 to 44 reported using contraception in 2011 to 2013. The pill was the most popular form of birth control, followed by female sterilization (which permanently blocks the fallopian tubes). Rounding out the top five methods were the male condom, long-acting reversible contraception (like intrauterine devices and implants) and male sterilization (vasectomy). In the survey, if women used more than one method, only the most effective method was counted.

And whats new for men? Their main mode of contraception, the condom, has been around for at least 400 years, perhaps longer. Alternatively, men who want to take the lead on family planning can go the surgical route with a vasectomy.

The dearth of alternatives is not due to a lack of research. Reproductive biologists and other researchers have made many exciting discoveries since the pill was introduced. But taking a promising finding in cells or in mice to human testing is hard for any drug. And for contraceptives, theres an extra wrinkle: Youre developing products for very healthy people, so you have to make sure [the drugs] are incredibly safe, and the side effect profile is acceptable, says Diana Blithe, a biochemist and chief of the contraceptive development program at the National Institute of Child Health and Human Development in Bethesda, Md.

Even with the long road to human testing, odds are that by the time the pill turns 75, there will be new options stocking the contraceptive cabinet. Researchers are currently exploring a method that keeps womens eggs in a state of suspended animation for later use. For men, there could be nonhormonal methods that stop sperm from developing and launching their epic journey. The impact of these novel methods might ripple out into society much as the pills once did.

There were 6.1 million pregnancies in the United States in 2011. Forty five percent of them, or a whopping 2.8 million, were not intentional, according to a 2016 report in the New England Journal of Medicine.

Unplanned pregnancies can have consequences for parents and kids, studies find. Womens education can be cut short. Unwanted pregnancies are linked to delayed prenatal care probably because moms dont realize theyre pregnant as well as low birth weight in infants. Postpartum depression is more common for mothers who did not intend to have a baby than for those who did.

The numbers also suggest that the contraceptives available arent meeting everyones needs. Some methods are expensive. And some users have health concerns or just dont stick with an option. In 2008, about 40 percent of unintended pregnancies were in couples that used contraception, but inconsistently, according to the Guttmacher Institute, a reproductive health research and policy organization in New York City.

Proportion of U.S. pregnancies in 2011 that were unplanned

From 2011 to 2013, the most popular reversible contraceptive choice for women ages 15 to 44 was the pill, with use at nearly 26 percent. The pill and other hormonal contraceptives contain the female sex steroid hormones estrogen and progesterone, or progesterone alone, usually in synthetic forms. These hormones prevent ovulation by suppressing the brains release of follicle-stimulating hormone and luteinizing hormone.

Some women find that hormonal contraceptives work well; other women experience side effects such as headaches, nausea, mood changes and acne. Oral contraceptives also increase the risk of blood clots, taking the drugs off the table for women with a history of blood clots, stroke or cardiovascular disease. The pill is also a no-go for women with severe hypertension or who have ever had breast cancer.

Relying on hormones to halt sperm production can also work. A new hormone-based gel for men, applied to the skin, is in human testing. It combines the male sex steroid testosterone with a synthetic progesterone. Plans are under way for couples to test the gel as their only form of birth control. But giving men hormones can come with side effects, such as reduced muscle mass and a drop in sexual function.

Discoveries that are beginning to explain the earliest stages of egg development and the finishing touches of sperm growth may lead to steroid-free alternatives.

Hormonal contraception disrupts ovulation, and the egg that was scheduled for departure from an ovary dies. But what if there was a method that preserved the egg for later?

When women are born, their ovaries have a full set of oocytes, or eggs a million or so. Each is housed within a sac of cells called a follicle. The outer portion of each ovary is filled with the earliest, dormant form of these egg-carrying follicles, called primordial follicles. The sleeping cells are waiting to be woken up, so they can begin growing in preparation for ovulation. But why the alarm clock goes off for one primordial follicle and not another is an open question, says reproductive biologist David Ppin of Massachusetts General Hospital and Harvard Medical School.

You could potentially preserve that pool of eggs for later in life, theoretically.

David Ppin

Todays hormonal contraceptives act on ovarian follicles that are already growing, and once that starts, there is no going back if ovulation doesnt happen, the egg dies. Aiming contraception at the sleeping eggs could mean putting off pregnancy, while holding on to the eggs. By preventing that first wake-up call, actually, you keep the egg, Ppin says. You could potentially preserve that pool of eggs for later in life, theoretically.

Meet the biological agent that could keep eggs asleep: Mllerian-inhibiting substance, or MIS. Also known as anti-Mllerian hormone, MIS is not a sex steroid hormone. It is produced in the developing testes and prevents male embryos from growing female reproductive parts. In adult female mice, MIS can also be a perpetual snooze button for primordial follicles, Ppin and colleagues, including Mass General and Harvard pediatric surgeon Patricia Donahoe, reported in the Feb. 28 Proceedings of the National Academy of Sciences.

Hundreds of follicles are estimated to be in various stages of development at any given time. The active growers release MIS locally, which limits the number of primordial follicles that wake up. This process allows the body to control and maintain the supply of eggs over a womans reproductive life span.

Primordial follicles, the sacs that house immature eggs, reside in the outermost region of the ovary. When follicles wake up, they begin to develop and move farther into the ovary. When a womans monthly menstrual cycle begins, follicle-stimulating hormone prompts additional growth of certain developing follicles. A dominant follicle matures. Luteinizing hormone helps the mature follicle open up, and the egg is ovulated and released into the fallopian tube. New experimental approaches to birth control aim to keep the primordial follicles dormant, so they can be available later in a womans life.

In their study, Ppin, Donahoe and colleagues used a virus to introduce a modified version of the MIS gene into certain cells in mice. This permanent change gave the mice a higher dose of MIS protein than is found normally in females. The follicles that had already been growing completed their development, but after that, no new follicles were activated, leaving a collection of sleeping-beauty primordial follicles.

When the researchers paired female mice treated with the gene therapy with males, the females were still able to become pregnant and have healthy babies within the first six weeks, because of those follicles that had already started growing in the ovaries. Once that supply was used up, the females were infertile.

Youre just stopping the horses that havent yet come out of the gate, Donahoe says.

To test a nonpermanent approach, the team gave normal female mice the MIS protein as a twice-daily shot. Activation of primordial follicles stopped. When treatment ended, the ovaries got back to business and follicles began growing again.

Ppin and Donahoe see several uses for MIS as a contraceptive. The permanent gene therapy method could be a nonsurgical contraceptive approach for pets or stray animals. The research team is working with the Cincinnati Zoo to study this method in cats.

Frequent shots of the MIS protein are too expensive for broad use, but they could help protect the reserve of ovarian follicles in young cancer patients. Growing follicles are dividing quite rapidly, so they are very sensitive to chemotherapy, Ppin says. Chemo can kill off the growing follicles, which means there is no more MIS to stop activation of other primordial follicles. Too many follicles wake up, which can deplete a womans egg supply. In mice given chemotherapy drugs, MIS-treated animals were left with more primordial follicles than untreated animals, the researchers found.

Still eager to make an MIS-like contraceptive for all women that is cheap and easy to use, perhaps as a pill, the researchers are searching libraries of small molecules to find one that mimics the action of MIS. Maybe it would be an already existing [U.S. Food and Drug Administration] approved medication thats the first screen we are performing or maybe its a very simple molecule, very cheap to synthesize, Ppin says.

Story continues below image

In the ovary of a normal mouse (left), a large follicle is shown at a late stage of development (a light pink oocyte surrounded by follicular cells, inset). In the ovary of a mouse treated with Mllerian-inhibiting substance, follicle development ceased and only primordial follicles were found (arrows, right).

In men, vitamin A does more than promote healthy eyes. Its essential for sperm production, too. The testes take up vitamin A from carrots and other foods and convert it to retinoic acid. The acid binds to the retinoic acid receptor, which is found in cells throughout the body.

In the 1990s, scientists reported that when they disrupted the gene for one version of the retinoic acid receptor, referred to as alpha, in mice, the animals are fine, but the males are sterile, says geneticist Debra Wolgemuth of Columbia University Medical Center. Wolgemuth and her colleagues, who study the biology of sperm production, set out to find a drug that could interfere with the receptor, rather than permanently knocking out the gene.

Wolgemuth came across a paper from 2001 by a group studying a drug that could bind to all three versions of the receptor, including alpha. The drug inactivates the receptor and shuts down the series of events that typically follow. Although tests in rats showed the drug could be taken orally and broken down safely by the body, the researchers highlighted one notable side effect. They called it testicular toxicity, Wolgemuth says.

Rather than a negative, Wolgemuth saw the toxicity as a sign of a potential male contraceptive. With molecular biologist Sanny Chung of Columbia and colleagues, she gave the drug to male mice for seven days, then examined their testes.

Sperm go through many stages of development as they transition from round germ cells to their final shape with a characteristic head and tail. Before sperm are released to begin their journey through the male reproductive system, says Wolgemuth, they line up like little soldiers in a battalion to leave the testes.

Story continues below image

In healthy mice, normal sperm line up at the center of a part of the testes known as the seminiferous tubule, ready for release (left, arrows). Mice treated with a drug that blocks whats known as the retinoic acid receptor have defective sperm that dont line up (right, arrows).

In mice treated with the drug, the sperm dont align properly, Wolgemuth and colleagues reported in 2011 in Endocrinology. The sperm arent released, so they die in the testes. The researchers found no evidence of harm to other organs. Male mice given the drug once a day for four weeks became infertile by the end of treatment and remained that way for four weeks after treatment stopped. By 12 weeks after treatment, the mice regained their mojo and successfully mated with females.

Later, the team gave mice a smaller dose of the drug for 16 weeks, over a quarter of their reproductive lives, notes Chung. The treated mice became sterile, but once off the drug, they soon became papas to healthy pups that grew into fertile adults, the researchers wrote in Endocrinology last year.

Next step: Wolgemuth plans to test the drug in nonhuman primates. Her group is also collaborating with a team of medicinal chemists to look for compounds that target only the alpha version of the retinoic acid receptor. Even though the tested drug did not lead to side effects, having an option that doesnt interfere with the other two versions of the receptor would be ideal, says Wolgemuth.

Another nonhormonal male contraceptive is the result of a long research career dedicated to such a product. In the late 1960s, Joseph Tash had two tours as a summer student in an obstetrics and gynecological department at Michael Reese Hospital in Chicago. He saw how heavily the burden of birth control fell to women. I felt it was important to try to expand the contraceptive and family planning choices to men, he says.

In 2013, the compound H2-gamendazole became the first nonhormonal contraceptive to receive FDA regulatory guidance, a crucial thumbs-up along the drug development road. Its a kind of checklist of the testing conditions and experiments necessary to proceed with preclinical and human trials.

Tash, now at the University of Kansas Medical Center in Kansas City, and colleagues began with an anticancer drug that, during clinical trials, severely cut down on sperm production. But there were a lot of side effects, Tash says, which would be totally unacceptable to otherwise healthy males. So the researchers designed similar drugs to minimize the side effects, including H2-gamendazole. Rats given a single oral dose of the drug once a week for six weeks became sterile after two weeks of use. By 10 weeks after the dosing stopped, all of the animals were fully fertile again.

The drug interferes with the last stage of sperm development, when the cells acquire their familiar sperm features. At this stage, as well as throughout the developmental process, sperm are tended to by Sertoli cells, which feed and support the growing sperm. The sperm are actually tethered to the Sertoli cells to prevent them from leaving the reef before they can swim.

H2-gamendazole disrupts the junctions between the sperm and the Sertoli cells, releasing the sperm prematurely and leading to their destruction. The testes have a built-in cleaning system, so to speak, that gets rid of the abnormal sperm, Tash says.

Tashs team has also tested H2-gamendazole in mice, rabbits, dogs and monkeys. In each animal, there was a block in sperm production just exactly like we see in the rats, Tash says. The team has also found that the drug can be taken as a pill and is rapidly taken up by the testes, at levels 10 to 20 times higher than in other tissues. I think this explains to a large extent why we havent seen any remarkable side effects, Tash says.

The work on H2-gamendazole, yet to be published, led to the FDAs regulatory guidance, a show of confidence in the drug. If Tash and colleagues can demonstrate to the FDA that the drug is safe and well tolerated, that might pique the interest of pharmaceutical companies to handle the final stages of testing and to take the drug to market. Its going to have to be a squeaky clean compound for pharma to become interested, Tash says.

Birth control methods born of these projects might shake things up outside the bedroom. If further testing finds that eggs kept asleep by an MIS-based contraceptive remain healthy and viable, delaying pregnancy may not necessarily lead to reduced fertility. A lot of women 35 and older are faced with reduced fertility, Ppin says. A method to target the activation of primordial follicles so you could keep them for later I think that would be beneficial.

Any new contraceptive options for men could shift the conversation men and women have about birth control. A multinational survey published in 2005 found more than half of men would be willing to use a new method of male birth control. There is an increasing number of men who are willing to help carry that burden, Tash says.

When that first product gets out there for men, Blithe adds, I think that will be a turning point.Any new contraceptive options for men could shift the conversation men and women have about birth control. A multinational survey published in 2005 found more than half of men would be willing to use a new method of male birth control. There is an increasing number of men who are willing to help carry that burden, Tash says.

This story appears in the Sept. 2, 2017 Science News with the headline, "Access denied: Scientists seek innovative ways to block the union of egg and sperm."

More here:
Birth control research is moving beyond the pill - Science News Magazine

Apic Bio Launches to Advance First-in-Class Gene Therapy for … – Business Wire (press release)

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Apic Bio, Inc., a pre-clinical stage gene therapy company leveraging its proprietary platform to advance therapies to treat rare diseases with complex mechanisms, in particular Alpha-1 Antitrypsin Deficiency (Alpha 1), launched today with an initial investment led by the venture philanthropy arm of the Alpha-1 Foundation and a private investor with the disease.

Its lead product, APB-101, targets the liver via an AAV delivered Dual Function Vector (df-AAV) whereby the Z-AAT protein is silenced and M-AAT protein is augmented. APB-101 has achieved a pre-clinical proof of concept with efficacy demonstrated in vitro and in vivo. It is currently undergoing pre-clinical GLP toxicology studies in non-human primates. Patients living with Alpha 1 lack sufficient levels of circulating AAT protein to protect lung tissue against damage from proteases, and experience the accumulation of mutant AAT polymers in the liver. Clinically, the deficiency is manifested by progressive emphysema and the accumulation presents a significant risk of liver cirrhosis.

John Reilly, Co-Founder & President said: We are grateful to TAP and A1AT Investors, LLC who have supported the successful start of Apic Bio by providing the first tranche of our seed financing round allowing us to secure key intellectual property rights and operational support. With such strong support from the advocacy and patient community, we are confident that we will identify the right corporate partners to help us achieve our business development goals and bring this exciting new therapy to patients.

The df-AAV platform allows treatment of other diseases with complex mechanisms where the mutant gene product must be reduced and the normal gene product must be augmented.

Dr. Chris Mueller, Co-founder and Chief Scientific Officer of Apic Bio said: We are encouraged by the feedback that we have received during our pre-IND meeting with the FDA that there is a clear path for us to conduct a first-in-human Phase 1/2 clinical study. Furthermore, we are very much looking forward to demonstrating the benefit of APB-101 to patients that have been living with alpha-1 and have had very little hope for a cure. Our data suggests this is a liver sparing approach for gene augmentation which may exceed the therapeutic and safety margins when compared to a strict gene augmentation without gene silencing that may exacerbate the underlying liver disease.

TAP is very pleased to provide this funding to Apic Bio. Their cutting-edge work on a therapy that addresses both the liver and lung disease brings us closer to finding a cure for Alpha-1 Antitrypsin Deficiency, thus fulfilling our mission, said Jean-Marc Quach, CEO for The Alpha-1 Project.

Todays launch of Apic Bio has been a long time coming for the hundreds of thousands of people who are challenged by Alpha 1, said Ed Krapels, who has been living with Alpha 1 and is the new companys first individual investor. Now that we are moving forward, we hope to work with patients, their advocates and researchers to make a cure readily available. Krapels added.

About Apic Bio: Apic Bio, Inc. is a spin-off from the University of Massachusetts Medical School (UMMS) and is based upon nearly 30 years of gene therapy research by its scientific founders Christian Mueller, PhD, Associate Professor of Pediatrics and a member of the Horae Gene Therapy Center at the University of Massachusetts Medical School, Terence R. Flotte, MD, the Celia and Isaac Haidak Professor in Medical Education, dean of the School of Medicine and provost and executive deputy chancellor of the University of Massachusetts Medical School; and colleagues at the Horae Gene Therapy Center. Their research is funded in part by an $11M grant from the National Heart, Lung, and Blood Institute (NHLBI).

View original post here:
Apic Bio Launches to Advance First-in-Class Gene Therapy for ... - Business Wire (press release)

Comic and Telethon Host Jerry Lewis Dies At 91 – WebMD

Aug. 21, 2017 -- Jerry Lewis, a consummate performer on stage and screen who used his fame to raise billions of dollars toward a cure for muscular dystrophy and other neuromuscular diseases, died Sunday at his home in Las Vegas. He was 91.

Born Joseph Levitch on March 16, 1926, in Newark, NJ, to vaudeville parents, Lewis wrote, appeared in, and directed 80-plus movies and TV shows over 5 decades in show business. He was memorable for his goofball antics and rubbery face (The Nutty Professor, The Bellboy, and The Ladies Man) and for his capacity for self-parody. Early in his career, he formed half of a comedy team with the late Dean Martin, with whom he hosted "The Martin and Lewis Radio Show" and made 16 films. In 1956, Lewis recorded an album (Jerry Lewis Just Sings) that made the Top 20 on the Billboard charts.

For many people, Lewis will be remembered best for raising awareness and money for the Muscular Dystrophy Association (MDA) during the 50-plus years he hosted the nationally televised Labor Day weekend telethon. In all, the shows raised more than $2 billion.

From 1956 until 2010, Lewis was the face of muscular dystrophy, a relatively rare neuromuscular disease that often begins in childhood and progressively robs a person of mobility. Lewis would wrap up the 21 1/2-hour annual show with a heartfelt version of Youll Never Walk Alone. He would typically sing it in a voice hoarse from hours of urging viewers to contribute to the cause, and probably from smoking on air throughout the broadcast.

In 1977, Lewis was nominated for a Nobel Prize for his 50 years of fighting muscular dystrophy.

(We) will be forever grateful to Jerry Lewis, a world-class humanitarian.

The reason for his stepping down as host of the telethon isnt clear -- The Hollywood Reporter wrote that he was unceremoniously dumped -- but Lewis never seemed to have talked about it publicly.

The MDA, on its website, praised Lewis efforts, saying it will be forever grateful to Jerry Lewis, a world-class humanitarian, for his indefatigable and inspiring work on behalf of kids and families with neuromuscular diseases, and for the countless dollars his commitment helped raise for critical research and services.

Perhaps Lewis left because the telethon, which had shrunk to a 2-hour show, had outlived its usefulness. In May 2015, the MDA announced it would end the telethon because of the expense and the realities of viewership and concentrate its fundraising on social media and other web-based channels.

The MDA raises money for medical research on 40 neuromuscular diseases, including Duchenne/Becker muscular dystrophy, the most prevalent form of MD, and amyotrophic lateral sclerosis (ALS), or Lou Gehrigs disease. In 2015, the organization said it was focusing support on gene therapy research and new drugs.

While Lewis did not suffer from a neuromuscular disease, he struggled with health issues for years. He had type 1 diabetes and pulmonary fibrosis, a condition in which tissue deep in the lungs scar and stiffen, making it more difficult for oxygen to get into the blood and causing shortness of breath. He suffered two heart attacks. He also had prostate cancer surgery in 1982. He had chronic back pain, which led to an addiction to the prescription painkiller Percodan, which he successfully replaced with an implanted device that dulls nerve impulses. In 2003, he had to wean himself off of steroids used to treat his lung disease.

Lewis last performances on stage were in March 2014, when he sold out two shows at La Mirada Theatre in California. He was 88 at the time, although he appeared in the 2016 film The Trust, with Nicolas Cage and Elijah Wood.

Lewis was divorced from Patti Lewis, with whom he had six children, and married SanDee Pitnick in 1983. They adopted a daughter together. In 2009, Lewis youngest son, Joseph, who struggled with drug addiction, committed suicide at age 45. In an interview he gave to The Hollywood Reporter in June 2014, Lewis was broken up by Josephs death, saying, To this day I don't understand it because it's unfair -- not unfair to me, but unfair to him. That he went that way made the unfairness stupidity. But he was my son and he's gone, and there's not a lot I can do about that. I beat myself a thousand times.

He was beloved throughout the world, but the French were particularly enchanted by Lewis. In 2006, for his 80th birthday, Lewis was awarded a medal and induction as a commander into the Legion of Honor, which is considered the highest decoration in France. It is akin to being knighted by the queen in England.

Lewis has two stars on the Hollywood Walk of Fame and received the Jean Hersholt Humanitarian Award at the 2009 Oscars ceremony. He received many other honors throughout this life, both for his humanitarian work and his work as a TV and movie star, and as a producer and director.

IMDb: Jerry Lewis Biography.

Biography.com: Jerry Lewis.

Muscular Dystrophy Association.

The Hollywood Reporter: At Home With Jerry Lewis as He Opens Up About Son's Death, Skirmishes With Fans.

The Associated Press: Jerry Lewis telethon ends decades-long run, fundraising awareness for Muscular Dystrophy Association.

CDC: Facts About Muscular Dystrophy.

Pulmonary Fibrosis Foundation.

CNN.com.

View original post here:
Comic and Telethon Host Jerry Lewis Dies At 91 - WebMD

Pacific Biosciences Is Advancing Genomics – Seeking Alpha

Pacific Biosciences of California (PACB) is a $480 million market cap company focused on development of innovative technologies and systems that impact diagnosis and treatment of disease and improve the world's food and energy supply. The company developed the Single Molecule, Real-Time (SMRT) Sequencing genomics technology, which enables real-time analysis of DNA synthesis. The company's technology can be used in human biomedical research to resolve heritability and variant types across populations or disease states.

Applications in plant sciences and agriculture include crop and livestock research acceleration via sequencing and transcriptome analysis. PACB technologies can also be used to characterize viruses and microbes of infectious disease, enabling the design of better vaccines and treatments.

So why would the reader be interested in PACB? The market for gene therapy applications are increasing at a CAGR of more than 20%, according to an analysis at Global Market Insights. In 2015, the gene therapy market was reported at over $800 million, and is expected to rise to $1.4 billion by 2024. The following figure depicts what this 20% growth looks like for a potential successful long investor. Nice, isn't it?

But gene therapies alone don't tell the whole story of market applications for genetic research tools. Cell therapy is an industry that plays a large role in applications for genetic analysis. The combined markets for cell and gene therapies are expected to rise from approximately $8 billion in 2018 to $12 billion in 2020. Strong Bio hopes that these predictive trend models can be useful for investors, and rather than focus on a company's pipeline in every article, it is striving to meet the needs of investors by focusing on some backstage players that have immense potential in advancing medical and agricultural research, such as PACB.

The rise in markets for gene therapies and cell therapies is expected to be driven by rapid technological advancement and increased adoption of new genomic techniques. Obviously, the largest market space in cell therapy and gene therapy application is cancer, with inflammatory disease also comprising a significant component of these potential markets. The World Health Organization predicts the number of new cancer cases will rise by as much as 70% over the next 20 years.

That is a lot of patients, and will fuel industry growth. In addition, favorable FDA regulation stances will serve cancer genetics industry growth in a positively weighted manner. Cancer genetics programs will begin to mainstream infrastructure to provide assays, informatics, and gene testing education to patients at hospital sites. Cancer will become a treatment regime reminiscent of chronic disease models, targeting specific molecules involved in specific patient's pathology.

The company sells its SMRT technology as a package product called Sequel System. SMRT supports numerous sequencing applications, bringing unique and novel depth and quality to genetic research. It is applicable in whole genome analysis for total genetic composition data of organisms including microbes, humans, plants, and animals. For instance, the company recently reported improving existing sequencing information for the maize plant genome, including fixing mistakes, reducing gaps, increasing sequence contiguity up to 50-fold, and adding difficult to reach (centromere region) sequences.

SMRT can be applied to produce in-depth analysis of genetic variations in disease models, using targeted approaches. It provides true long read lengths and highest consensus accuracy available, revealing a full spectrum of genetic variation for microbes and virus, and heterologous cell populations such as escaping cancer cell genomes. PACB SMRT technology offers RNA isoform sequencing functions that can produce full-length transcripts (eliminating the need for assembly, useful in transcriptome analyses). Epigenetic characterization of DNA modifications in prokaryotic and eukaryotic models are also possible.

The company recently announced an agreement by Novogene (China) to purchase ten Sequel systems in addition to ten already purchased earlier this year. To date Novogene is the largest user of PACB Sequel systems, and the reordering of technology indicates customer satisfaction and increased productivity.

Novogene and PACB have agreed to co-market and promote genomic applications. The company cites high demand by Novogene as impetus to double its production capacity to meet the orders, driven by a Chinese precision medicine initiative to sequence variants in 1000 individuals. The company is also participating in other world genome discovery projects.

Net loss for 2Q 2017 was $25.5 million, compared to $18.5 million for the second quarter of 2016. Operating expenses for 2Q 2017 was $32.4 million, compared to $28.7 million for 2Q 2016. The company reported $20.1 million in 2Q 2017 product, service, and other revenue compared to $17.2 million for 2Q, 2016. Cash and cash equivalents at end Q2 2017 was $102.6 million, compared to $72.0 million at December 31, 2016. In June 2017, the company did an offering of approximately 15 million shares at $3.10 per share, raising approximately $46 million.

Strong Bio wants to emphasize that the era of gene therapy is upon us, and several candidates are likely to be approved as potential first gene therapy products approved by FDA later this year. Emerging supportive technologies stand to benefit as the medical system and biotechnology investment centers begin to realize the fruits of such endeavors.

PACB is right in there for the upcoming revolution. To give the reader an idea of the power of its technology on client bottom line, the Sequel system was able to do the maize genomic work at a cost of around $20,000 per maize line, compared to the nearly $30 million in cost for the original maize genome reference.

It is well-positioned in the industry, with its technology being referenced in over 35 presentations at annual AGBT 2017 conference, demonstrating customer value. Over 135 references to PACB technology were made in the 2017 annual PAG conference. The stock has jumped a bit after announcing the sale of 10 Sequel units, but would be attractive on a pullback into the gap to the $3.00 offering range, and is thus watchlisted as an exciting prospect. It is also possible that some consolidation in this space could occur, leading to potential merger and acquisition action. Yahoo consensus target of 4 analysts is $5.95 per share.

Risks for investment in PACB include industry dynamics that the high cost of developing new treatments impedes growth in the gene therapy industry. Moreover, no gene therapy products have yet been approved by the FDA. However, advancements in rare diseases using the gene therapy/genomic approach are coming soon. It is clear that cell therapies that involve genomic research will offset the slow-to-start gene therapy development costs impediment, and serve as a catalyst for profitable efforts to fund gene therapies as they enter the market over the coming months and years.

Another risk for investors is that the company is not yet close to a cash-neutral revenue stream, so further dilution could be possible. There is some competition in the genomics industry as well, but Strong Bio regards SMRT as a front-runner in the space. One could have argued 20 years ago that there is no obvious value in sequencing genomes, but given the breakthroughs that are upon us in the upcoming gene therapy era, the time to place investments is rapidly drawing near. The reward to risk ratio for PACB is compelling.

Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.

I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

Originally posted here:
Pacific Biosciences Is Advancing Genomics - Seeking Alpha

Scientists foresee Russian gene therapy for HIV cure may be registered in 5-10 years – TASS

MOSCOW, August 17. /TASS/. A Russian gene therapy drug for individuals infected with HIV called Dinavir is undergoing pre-clinical trials, and the drug has already proved its efficiency on cells. The pre-clinical tests on animal models, clinical trials and the registration procedure may take up to 10 years, senior research fellow at the Epidemiology Central Research Institute of Rospotrebnadzor (the Federal Service on Surveillance for Customers Rights Protection and Human Well-Being) Dina Glazkova told TASS.

"This is not about the next year, but rather in five years, at the earliest. It takes up to 10 years on the average," she said.

Glazkova reiterated that the registration is made after the clinical trials. "Again, the clinical trials are costly, and the drug production is costly as well," the scientist added.

Dinavir proved to be safe while tested on cells, in vitro. A Phase II pre-clinical trial will utilize animal models to test the efficiency and safety of treatment. A Phase I clinical trial will be carried out on humans to test safety of the therapy and will take up not less than a year.

"Phase II takes up two to three years, and it is unclear how much will be required from us. Phase I is about safety, and it takes a few patients: five, maybe ten. Phase II is when we have to prove that the drug works in these five to ten [patients] and that it had a positive effect on them. Phase III is when we enroll a lot of patients [in the trial] to show that the five were cured not by accident and that it [the gene therapy] really works," Glazkova explained.

The gene therapy for HIV treatment is being developed by a group of researches at the Epidemiology Central Research Institute of Rospotrebnadzor.

See the original post here:
Scientists foresee Russian gene therapy for HIV cure may be registered in 5-10 years - TASS

Why three little virus-free pigs matter – The Messenger (subscription)

We've done some genetics. We've done DNA. We've done GMOs. We've done some immunology. We've done science literacy. Now, let's get down in the weeds a little bit and put all of that together to look at just exactly why virus-free piglets are news.

Aren't piglets just the cutest things? The three particular precious petite porkers in the picture have recently been making the rounds of the national news, usually under a headline that says something like "Scientists create virus-free pigs." This is an excellent example of a headline that really fails to do what a headline is supposed to, which is capture the reader's interest. Virus-free pigs. Big whoop.

If, however, you got past the lame headlines and you've read any of those stories, you know that this is sort of a big deal, on several different levels, and we'll use what we've already talked about in some of my earlier articles about genes, viruses, DNA, genetic engineering, and the value of science literacy to explore why these three little pigs are important.

These pigs are really just like any other pigs, except they were born without any genes in their genomes that code for a number of viruses found in all other pigs, called porcine endogenous retroviruses, or PERVs (yeah, I know. Not that kind of perv). Let's talks about what the term means and what PERVs are. The word "porcine" just means "related to pigs." "Endogenous" means "something that is normally found in or originating from within an organism." For instance, insulin is an endogenous human hormone, because it is produced by the pancreas and is normally present in people. "Retroviruses" are a group of viruses that use RNA (ribonucleic acid) instead of DNA (deoxyribonucleic acid) as their genetic material.

When a virus of any kind infects a cell, the reproductive machinery of the cell, which is normally used to make proteins and copy the DNA of the cell so that the cell can divide and reproduce, is hijacked by the virus. The virus causes the cell to make new copies of the viral genome and then to use the viral genes to make viral proteins. When the cell makes the new viral proteins, they are assembled into new viruses and the new viruses then can go out to infect other cells. Usually, the cell is destroyed in the process. Sometimes, though, the viral genes just get integrated into the genome of the infected host cell and the cell goes on living and reproducing as normal, only now, every time the cell divides, the new cell also has a copy of the viral genes in its DNA.

Sometimes, the viral genes just sit there, causing no

problems. This is called a "latent virus." It may sit there forever doing nothing, or sometimes, something happens to activate the latent virus and the viral genes start to be reproduced, viral proteins start to be made by the infected cells and that may cause disease. The Herpes simplex family of viruses is an example of latent viruses. Other examples of latent viruses are called retroviruses. In a retrovirus, the RNA from the retrovirus is used as a template to make DNA in the infected cell, and then the DNA becomes integrated into the host cell's genome. HIV is an example of a retrovirus that affects humans.

If you look at the genome of almost any organism, particularly complex organisms, like most of us, there is a lot of what is called "non-coding DNA." Non-coding DNA is exactly that -- it doesn't code for any specific proteins. There is some disagreement on whether this non-coding DNA has any function at all, but the amount of it is pretty amazing. Somewhere between 80 percent and 98 percent of the human genome is non-coding. This was a bit of a surprise when the Human Genome Project was going on in the 1990s.

The Human Genome Project was a very ambitious, very wide-ranging effort to identify all the genes in the human genome and map the location where each gene would be found on our chromosomes. The early expectation was that the human genome, based on the amount of DNA it contains (along with human ego), would contain hundreds of thousands of, possibly a million, individual genes. After all, something as marvelous as we are would obviously have the most genes of any creature, right? Wrong. The initial findings of the genome project was that humans have about 30,000 individual genes that code for proteins. This low number was quite the surprise. After all, there is a single-celled protozoan that has over 60,000 genes. There is a plant that has a genome almost three times the size of the human genome. Talk about you rude awakenings! Here we are, thinking how complex and wonderful we are, and there are flowers and pond scum with larger, more complex genomes than ours!

So, what does this have to do with our story today? Well, with the discovery that the vast majority of the human genome, and the genomes of most complex organisms, for that matter, doesn't code for proteins, it begs the question, "then why is it there and where did it come from?" Both of those are good questions that haven't been fully answered, but part of that "extra" DNA is probably DNA that originated long, long ago in our evolutionary history as viral DNA that got integrated into our own genome. The same is likely true for much of the PERV DNA in pigs.

In the case of PERVs, the viruses are found in most of the pig's cells, including the sperm and egg cells used in reproduction. Because they are in the reproductive cells, newborn pigs are already infected with the virus. The PERVs don't normally cause any disease in the pigs, as they usually remains latent in pig cells. The problem with PERVs is that they can be transferred to humans and infect human cells when pig organs or tissues are transplanted into people and PERVs can potentially cause disease in humans.

This is why scientists bothered to try to make virus-free pigs. Pigs have long been used as a source of organs and tissues for transplantation into humans. One reason for this is that the anatomy and physiology of pigs is very similar to that of humans, and so many of their organs and tissues are very similar to those of humans. Pigs and people are also of similar size, so swapping out parts works pretty well because, for instance, a heart valve from a pig is just about the same size as a heart valve from a human. Producing pigs that have tissues free of PERVs is a big step into making pig organs more available and safer for transplantation into humans.

The cute little virus-free piggies in the picture were created using a couple of genetic engineering techniques that are both revolutionary and controversial. The first technique is a new technology called CRISPR (pronounced "crisper"). It stands for "Clustered, Regularly Interspaced Short Palindromic Repeats." I'm not going to go into what all that means. What I will say is that it takes advantage of a genetic mechanism used by bacteria to avoid being infected by viruses. Yes, bacteria can be, and often are, infected by viruses. The CRISPR technology allows scientists to target specific gene sequences in the DNA of a cell, cut it out and replace it with a new gene sequence. CRISPR is hugely valuable in genetic research and has great promise in therapeutic use to treat genetic diseases. Theoretically, CRISPR could be used to cut out defective genes in a patient with a genetic disease and replace the bad gene with a good one. That sort of application is quite a way off. In the case of our pigs, however, CRISPR was used to cut out the genes for all the PERVs found in pig cells that were grown in a dish. The result of that was pig cells that were completely free of PERVs.

The second controversial technique that was used is called "somatic cell nuclear transfer." A somatic cell is just a term for any of the regular, non-reproductive cells found in an organism. In this technique, the nucleus of a cell, where all the genetic material is located, is removed. That nucleus is then transferred into another cell, from which the nucleus has also been removed, essentially turning the recipient cell into a genetic copy of the donor cell. If the recipient cell is a reproductive cell, like an egg cell, and the egg is fertilized, the genes contained in the donor cell will be present in all the cells that develop from the fertilized egg. In this case, the nuclei from the cells grown in the dish that were modified to be PERV-free were injected into fertilized pig eggs. The eggs were then implanted into surrogate mother pigs and they developed into our piglets.

This technology has incredible potential in transplant therapeutics, as well as gene therapy to correct some horrible diseases. Somatic cell nuclear transfer also has another name -- cloning. Dolly the Sheep, if you remember her, was the first mammal to be produced through cloning. The term "cloning" brings up all sorts of late-night horror movie terrors and visions of genetically engineered babies and so on. In reality, cloning is not fearsome or evil. It is just a fairly simple, very powerful tool in the field of genetic research.

However, here is where the science literacy part of the story comes into play. These techniques were used, in this case, as a step toward improving options for transplanted organs and tissues. It is theoretically possible, however, that these same techniques could be used for less clearly beneficial ends. It could, for instance, be further developed and adapted to be used to modify human embryos to create "designer babies." Clearly, this is an issue with profound bioethical considerations. It is important that we, as a human society, understand this science, and that includes you.

This technology, like other forms of genetic engineering, stem cell-based therapeutics, artificial intelligence, GMOs, and other equally powerful, potentially transformative science, could be hugely valuable in improving the human condition if used properly, but the consequences of abuse of the technology are also huge. We must be part of a well-informed populace to make reasoned, rational decisions on how we want our science to be used.

Already, the scientific communities of the U.S., UK, China, and others have set strict guidelines on what types of research along the lines of that which produced our virus-free pigs is permissible, but as science moves forward, there will need to be more discussion. The benefits and consequences of these technologies are so huge that we must discuss them from a position of knowledge and understanding, not from one of fear, ignorance and emotion. This is why it is so vitally important for everyone to be scientifically literate.

Michael J. Howard, Ph.D., is the vice president fo education and research at Baptist Health Madisonville. He can be reached by email at madisonvillescience@gmail.com or via Twitter at @madville_sci.

View original post here:
Why three little virus-free pigs matter - The Messenger (subscription)

Cancer Gene Therapy Market – Forecasts and Opportunity Assessment by Technavio – Business Wire (press release)

LONDON--(BUSINESS WIRE)--According to the latest market study released by Technavio, the global cancer gene therapy market is expected to grow at a CAGR of almost 21% during the forecast period.

This research report titled Global Cancer Gene Therapy Market 2017-2021 provides an in-depth analysis of the market in terms of revenue and emerging market trends. This market research report also includes up to date analysis and forecasts for various market segments and all geographical regions.

The rising prevalence rate of cancer has been a huge challenge for the global economies as the disease leads to high rate of mortality and economic losses. The current treatment options available come with many drawbacks such as severe side effects and relapse of cancer. These factors have led to high investment in the R&D for development of various novel therapies with cancer gene therapy being one of the major ones of them. The therapy mainly uses three types of treatment options namely oncolytic virotherapy, gene transfer therapy, and gene-induced immunotherapy.

This report is available at a USD 1,000 discount for a limited time only: View market snapshot before purchasing

Buy 1 Technavio report and get the second for 50% off. Buy 2 Technavio reports and get the third for free.

Technavios healthcare and life sciences research analysts categorize the global cancer gene therapy market into the following segments by therapy. They are:

Looking for more information on this market? Request a free sample report

Technavios sample reports are free of charge and contain multiple sections of the report including the market size and forecast, drivers, challenges, trends, and more.

Oncolytic virotherapy

Oncolytic virotherapy is one of the fastest growing treatment modality. In this therapy, the anti-cancer cells specifically destroy the cancer cells without causing harm to the normal cells. Each virus has a specific cellular tropism that determines which tissue will be preferentially infected by the virus and thus will further lead to the disease.

According to Sapna Jha, a lead oncology research analyst from Technavio, The oncolytic virotherapy has shown encouraging results in the pre-clinical studies. The novel treatment option holds great opportunity to make a significant effect on quality and length of the life of the individual. Adenovirus is the most commonly used virus in oncolytic virotherapy.

Gene transfer

Gene transfer or gene insertion is one of the most exciting and emerging cancer treatment methods. The therapy is expected to be the fastest growing type of therapy in the cancer gene therapy market. This is a radical new treatment method that involves the introduction of a new gene into the cancer cell or the surrounding tissues.

Genes with different functions have been proposed for this therapy; some of them include antiangiogenesis genes, cellular stasis genes, and suicide genes. Many different viral vectors are used to deliver these genes, Adenovirus being most common of them. Other than viral vectors, certain non-viral methods are also studied in the various clinical trial, which includes oligodendromer DNA coatings and naked DNA transfer, adds Sapna.

Gene-induced immunotherapy

Immunotherapy works on the concept of boosting the immune system of the individual to target and destroy cancer cells. However, traditional immunotherapy has shown limited success rate in the field. Various gene therapy techniques are being used to overcome this limitation.

The next-generation gene-induced immunotherapy vaccines are already in clinical trial. Gene-induced immunotherapy is a type of gene therapy where genetically engineered genes are used to generate an immune response against cancer. Growing knowledge and understanding of mechanisms regulating the initiation and maintenance of cytotoxic immune response has led to the designing of several genetic immunization strategies.

The top vendors highlighted by Technavios research analysts in this report are:

Browse Related Reports:

About Technavio

Technavio is a leading global technology research and advisory company. Their research and analysis focuses on emerging market trends and provides actionable insights to help businesses identify market opportunities and develop effective strategies to optimize their market positions.

With over 500 specialized analysts, Technavios report library consists of more than 10,000 reports and counting, covering 800 technologies, spanning across 50 countries. Their client base consists of enterprises of all sizes, including more than 100 Fortune 500 companies. This growing client base relies on Technavios comprehensive coverage, extensive research, and actionable market insights to identify opportunities in existing and potential markets and assess their competitive positions within changing market scenarios.

If you are interested in more information, please contact our media team at media@technavio.com.

Go here to see the original:
Cancer Gene Therapy Market - Forecasts and Opportunity Assessment by Technavio - Business Wire (press release)

Gene Therapy | Pfizer: One of the world’s premier …

Gene therapy is a technology aimed at correcting or fixing a gene that may be defective. This exciting and potentially transformative area of research is focused on the development of potential treatments for monogenic diseases, or diseases that are caused by a defect in one gene.

The technology involves the introduction of genetic material (DNA or RNA) into the body, often through delivering a corrected copy of a gene to a patients cells to compensate for a defective one, using a viral vector.

The technology involves the introduction of genetic material (DNA or RNA) into the body, often through delivering a corrected copy of a gene to a patients cells to compensate for a defective one, using a viral vector.

Viral vectors can be developed using adeno-associated virus (AAV), a naturally occurring virus which has been adapted for gene therapy use. Its ability to deliver genetic material to a wide range of tissues makes AAV vectors useful for transferring therapeutic genes into target cells. Gene therapy research holds tremendous promise in leading to the possible development of highly-specialized, potentially one-time delivery treatments for patients suffering from rare, monogenic diseases.

Gene therapy research holdstremendous promise

Pfizer aims to build an industry-leading gene therapy platform with a strategy focused on establishing a transformational portfolio through in-house capabilities, and enhancing those capabilities through strategic collaborations, as well as potential licensing and M&A activities.

We're working to access the most effective vector designs available to build a robust clinical stage portfolio, and employing a scalable manufacturing approach, proprietary cell lines and sophisticated analytics to support clinical development.

In addition, we're collaborating with some of the foremost experts in this field, through collaborations with Spark Therapeutics, Inc., on a potentially transformative gene therapy treatment for hemophilia B, which received Breakthrough Therapy designation from the US Food and Drug Administration, and 4D Molecular Therapeutics to discover and develop targeted next-generation AAV vectors for cardiac disease.

Gene therapy holds the promise of bringing true disease modification for patients suffering from devastating diseases, a promise were working to seeing become a reality in the years to come.

Continue reading here:
Gene Therapy | Pfizer: One of the world's premier ...

Listening for the Public Voice – Slate Magazine

Jupiterimages/Thinkstock

On Aug. 3, the scientific article in Nature finally gave us some facts about the much-hyped experiments that involved editing the genomes of human embryos at the Center for Embryonic Cell and Gene Therapy at Oregon Health and Science University. The story had broken in late July in Technology Review, spurring profuse hand-wringing and discussion. But until we saw the scientific paper, it was not clear what cells and methods were used, what genes were edited, or what the results were.

Now we know more, and while the paper demonstrates the possibility of genome editing of human embryos, it raises more questions than it answers. It is a useful demonstration of technical promise, though not an immediate prelude to the birth of a genome-edited baby. But the process by which the news emerged is also an ominous harbinger of the discombobulated way the debate about genetically altering human embryos is likely to unfold. We need open, vigorous debate that captures the many, often contradictory, moral views of Americans. Yet what we are likely to get is piecemeal, fragmented stories of breakthroughs with incomplete details, more sober publication in science journals that appear later, news commentary that lasts a few days, and very little systematic effort to think through what policy should be.

The science underlying this news cycle about human genome editing builds on a technique first developed six years ago by studying how bacteria alter DNA. CRISPR genome editing is the most recent, and most promising, way to introduce changes into DNA. It is faster, easier, and cheaper than previous methods and should eventually be more precise and controllablewhich is why it may one day be available for clinical use in people.

Though headlines about the study discussed designer babies, researchers prefer to emphasize how these techniques could help stop devastating genetic disorders. The Oregon experiments with human embryo cells corrected disease-associated DNA variants associated with heart muscle wasting that can cause heart failure. The treated embryos were alive for only a few days and were never intended to become a human baby. They were, however, human embryos deliberately created for the research.

U.S. guidance in this area is sparse and reflects the lack of societal consensus. In 1994, when the federal government was contemplating funding for research involving human embryos, the NIH Embryo Research Panel concluded that just this kind of experiment was ethically appropriate. But within hours of that reports release, then-President Bill Clinton announced he did not agree with creating embryos in order to do research on them.

The United States currently has just two policies relevant to genomic editing of human embryos. The first blocks federal funding: On April 28, 2015, Francis Collins, director of the National Institutes of Health, stated, NIH will not fund any use of gene-editing technologies in human embryos. This is not embedded in statute or formal executive order, but members of Congress are fully aware of it and it is, in effect, a federal policy. NIH can (and does) fund genome editing of nonembryonic cells that might be used to treat cancer and for other possible therapeutic purposes, but not embryonic cells that would have their effect by creating humans with germline alterations.

Second, Congress has prohibited the Food and Drug Administration from reviewing research in which a human embryo is intentionally created or modified to include a heritable genetic modification. This language comes from a rider to FDAs annual appropriations. Yet use of human embryonic cells for treatment should be subject to FDA regulation. So this language in effect means alterations of embryonic cells cannot be done in the United States if there is any intent to treat a human being, including implantation of an altered embryo into a womans uterus. This will remain true so long as the rider is included in FDAs annual appropriations. The federal government thus has two relevant policies, both of which take federal agencies out of the action: One removes NIH funding, and the other precludes FDA oversight of genome-edited human embryos.

This leaves privately funded research that has no direct therapeutic purpose, such as with the Oregon experiments. The funding came from OHSU itself; South Korean Basic Research Funds; the municipal government of Shenzhen, China; and several private philanthropies (Chapman, Mathers, Helmsley, and Moxie). The research complies with recommendations to study the basic cellular processes of genome editing, keeping an eye on possible future clinical use but only so long as the work does not attempt to create a human pregnancy.

By coincidence, on the same day the Nature paper came out, the American Journal of Human Genetics also published a thoughtful 10-page position statement about germline genome editing from the American Society for Human Genetics endorsed by many other genetic and reproductive medicine organizations from all over the world. It reviews recommendations of the National Academies of Sciences, Engineering, and Medicine, several international and U.S.-based organizations and commissions, and makes several recommendations of its own, concluding it is inappropriate to perform germline gene editing that culminates in human pregnancy, but also there is no reason to prohibit in vitro germline genome editing on human embryos and gametes, with appropriate oversight and consent from donors, to facilitate research on the possible future clinical applications. Indeed, the statement argues for public funding. Finally, it urges research to proceed only with compelling medical rationale, strong oversight, and a transparent public process to solicit and incorporate stakeholder input.

So is there a problem here? It is truly wonderful that medical and scientific organizations have addressed genome editing. It is, however, far from sufficient. Reports and scientific consensus statements inform the policy debate but cannot resolve it. All of the reports on genome editing call for robust public debate, but the simple fact is that embryo research has proven highly divisive and resistant to consensus, and it is far from clear how to know when there is enough thoughtful deliberation to make policy choices. Its significant that none of the reports have emerged from a process that embodied such engagement. The Catholic Church, evangelical Christians, and concerned civic action groups who view embryo research as immoral are not likely to turn to the National Academies of Sciences, Engineering and Medicine, the American Society for Human Genetics, the Hinxton Group, the Nuffield Council on Bioetics, or other scientific and medical organizations for their primary counsel. They may well listen to scientists, but religious and moral doctrine will get greater weight. Yet religious groups highly critical of embryo research are part of the political systemand whether we embrace this sort of genome editing in the United States is a political question, not a purely technical one.

Reports and scientific consensus statements inform the policy debate but cannot resolveit.

Addressing the political questions will be extremely difficult. The U.S. government is poorly positioned to mediate the policy debate in a way that recognizes and addresses our complex moral pluralism. NIH and FDA are two of the most crucial agencies, but current policies remove them from line authority, and with good reason, given that engaging in this debate could actually endanger the agencies other vital missions. International consensus about genome editing of human embryos remains no more likely than about embryo research in general: Some countries ban it while others actively promote and fund it. Private foundations dont have the mandate or incentive to mediate political debate about a controversial technology that rouses the politics of abortion. What private philanthropic organization would willingly take on such a thankless and politically perilous task, and what organization would be credible to the full range of constituencies?

So who can carry out the public engagement that everyone seems to agree we need? The likely answer is no one. This problem occurs with all debate about fraught scientific and technical innovations, but its particularly acute when it touches on highly ossified abortion politics.

The debate about genomic editing of human embryos is unlikely to follow the recommendations for systematic forethought proposed by illustrious research bodies and reports. Given the reactions weve seen to human embryonic stem-cell research in the past two decades, we have ample reason for pessimism. Rather, debate is more likely to progress by reaction to events as researchers make newsoften with the same lack of information we lived with for the last week of July, based on incomplete media accounts and quotes from disparate experts who lacked access to the details. Most of the debate will be quote-to-quote combat in the public media, leavened by news and analysis in scientific and medical journals, but surrounded by controversy in religious and political media. It is not what anyone designing a system would want. But the recommendations for robust public engagement and debate feel a bit vacuous and vague, aspirations untethered to a concrete framework.

Our divisive political system seems fated to make decisions about genomic editing of human embryos mainly amidst conflict, with experts dueling in the public media rather than through a thoughtful and well-informed debate conducted in a credible framework. As the furor over the Oregon experiments begins to dissipate, we await the event that will cause the next flare-up. And so it will continue, skipping from news cycle to news cycle.

History shows that sometimes technical advances settle the issues, at least for most people and in defined contexts. Furor about in vitro fertilization after Louise Brown, the first test tube baby, was born in 1978 gave way to acceptance as grateful parents gave birth to more and more healthy babies and welcomed them into their families. Initial revulsion at heart transplants gave way in the face of success. Anger about prospects for human embryonic stem-cell research might similarly attenuate if practical applications emerge.

Such historical examples show precisely why reflective deliberation remains essential, despite its unlikely success. Momentum tends to carry the research forward. Yet at times we should stop, learn more, and decide actively rather than passively whether to proceed, when, how, and with what outcomes in mind. In the case of genome editing of human embryos, however, it seems likely that technology will make the next move.

This article is part of Future Tense, a collaboration among Arizona State University, New America, and Slate. Future Tense explores the ways emerging technologies affect society, policy, and culture. To read more, follow us on Twitter and sign up for our weekly newsletter.

Read more from the original source:
Listening for the Public Voice - Slate Magazine

Pfizer commits $100M for a gene therapies plant in North Carolina – FiercePharma

Pfizer committed to building a $100 million gene therapies plant in North Carolinaand in exchange, North Carolina committed to providing the drugmaker with a quarter-million dollars' worth of help.

Pfizer will expand an 11,000-square-foot plant in Sanford, North Carolina that it acquiredlast year when it bought gene therapies biotech Bamboo Therapeutics in a deal valued at up to $688 million.Bamboo bought the facilitylast year from the University of North Carolina about the time that Pfizer made is initial investment in the company.

The drugmaker considered building a facility in Massachusetts where it has other research and manufacturing operations but decided on North Carolinawhere it will receive a $250,000 performance grant from the state for the project and its 40 jobs.

RELATED:Pfizer looks at building major gene therapy manufacturing facility in North Carolina

Pfizer is proud to further expand our presence in North Carolina, particularly as we build our leadership in gene therapy, Lynn Bottone, site leader at Pfizer Sanford said in a statement. We look forward to the next phase of this expansion as we build a clinical and commercial manufacturing facility.

A Pfizer spokeswoman said in an email Tuesday that it was too early in the process to provide any details about the size of the expansion or when it might be producing materials.

Bamboo has already produced phase I and II materials in the facility using what Pfizer said was superior suspension, cell-based production platform that increases scalability, efficiency and purity.

Bamboo is working on gene therapies for certain rare diseases related to neuromuscular conditions and the central nervous system. With gene therapies, genetic material is introduced into a patients body to replacemutations that cause diseaseand the expectation is that treatments may cure the condition.

RELATED: Pfizer doubles down on gene therapy pipeline with $70M Sangamo buy-in

Pfizer is among a number of companies exploring the new area and added to its portfolio this spring when it struck a licensing deal with Richmond, California-based Sangamo Therapeutics, which is working on gene therapies for treating hemophilia A. Under the deal, Sangamo got $70 million upfront and could gain $475 million in biobucks and sales royalties on any medications from the collaboration that gain approval.

Others are building manufacturing facilities as well. California-based BioMarin, recently completed the renovation of a 25,000-square-foot building in Novato, Novato, California, for manufacturing the gene therapies for hemophilia A which its has in clinical trials, the Marin Independent Journal reported Monday.

See the original post here:
Pfizer commits $100M for a gene therapies plant in North Carolina - FiercePharma

Grant enables study of mosquito virus as a genetic lab tool, malaria biocontrol – Penn State News

UNIVERSITY PARK, Pa. A virus that infects a species of malaria-transmitting mosquito could help scientists gain a better understanding of mosquito biology and eventually could lead to methods for stopping or slowing the spread of the disease, according to a researcher in Penn State's College of Agricultural Sciences.

Jason Rasgon, professor of entomology, has received a grant of $1.9 million from the National Institutes of Health to study the virus, called AgDNV. The goal of the five-year project is to develop a toolset that would enable researchers to genetically modify mosquitoes more easily, with an eye toward examining the influence of specific genes on mosquito phenotypes and developing malaria-control strategies.

"This project involves Anopheles gambiae, the main mosquito vector of malaria in Africa," Rasgon said. "Routine genetic manipulation of this species has proven challenging, so the development of novel tools for genetic modification is critical for both applied strategies for malaria control and for basic research into this mosquito's genetics and host-pathogen interactions."

To prove the feasibility of this concept, the research team will insert specific genes into a densonucleosis virus known as a "densovirus" which will infect the mosquito's tissues and express those genes.

"This virus is distantly related to the virus used in human gene therapy," Rasgon said. "So it's almost like gene therapy in the mosquito."

He explained that the densovirus is a tiny virus it contains only three genes and about 4,100 nucleotides and its entire genome can be synthesized artificially and placed into a plasmid, which is a circular piece of DNA.

"Once in that form, we easily can manipulate it and transfect it into insect cells in a dish, where it will make live, infectious virus that will have whatever genetic modifications we've put into it," said Rasgon.

Researchers then can infect mosquitoes either by putting the virus into water with mosquito larvae or by injecting it into adult mosquitoes. The virus then will infect them, and whatever gene was inserted will be expressed.

An Anopheles gambiae mosquito infected with AgDNV (virus) expressing green fluorescent protein.

Rasgon said this system would have great value as a laboratory tool: "If you want to test a gene by turning it on or off, you wouldn't need to develop a transgenic mosquito. You just could pop it into the virus, and it will express that gene in the mosquito for you."

It also could become a biocontrol agent, he said. "You could insert genes that would make the mosquito unable to transmit the malaria parasite or that would kill the mosquito or shorten its lifespan."

This specific virus occurs naturally and would be very safe as a control agent, Rasgon noted. The virus is not a human pathogen and is host-specific, meaning it infects only Anopheles gambiae and not other mosquitoes or nontarget organisms such as vertebrates.

In addition, once infected by the modified virus, adult female mosquitoes can transmit it to larvae by inoculating it into the water when laying eggs. Rasgon's lab also has found that male adult mosquitoes can transmit the virus to females during mating.

Rasgon maintains that this line of research illustrates the unpredictability and serendipity of science he discovered the existence of the virus by accident about 10 years ago.

"We were looking for a particular bacterium in a mosquito cell line using PCR [polymerase chain reaction], and we got a weird band where there shouldn't have been one," he said. "We wanted to know what it was so we sequenced it, and it turned out to be this virus.

"We've been unsuccessfully seeking funding to study it further for 10 years. So receiving this grant also is a testament to the value of persistence in science," he said.

Excerpt from:
Grant enables study of mosquito virus as a genetic lab tool, malaria biocontrol - Penn State News

Skewing the Aim of Targeted Cancer Therapies – Research Horizons

[Note to researchers: mRNA-protein level disparities found in metastatic ovarian cancer in more than 60% of measurements across 4,436 genes; evidence of micro RNA regulation]

Headlines, of late, have touted the successes of targeted gene-based cancer therapies, such as immunotherapies, but, unfortunately, alsotheir failures.

Broad inadequacies in a widespread biological concept that affects cancer research could be significantly deflecting the aim of such targeted drugs,according to a new study. A team exploring genetic mechanisms in cancer at the Georgia Institute of Technology has found evidence that a prevailing concept about how cells produce protein molecules, particularly when applied to cancer, could be erroneous as much as two-thirds of the time.

Prior studies by other researchers have also critiqued this concept about the pathway leading from genetic code to proteins, but this new study,led by cancer researcher John McDonald, has employed rare analytical technology to explore it in unparalleled detail. The study also turned up novel evidence for regulating mechanisms that could account for the prevailing concepts apparent shortcomings.

The concept stems from common knowledge about the assembly line inside cells that produces protein molecules. It starts with code in DNA, which is transcribed to messenger RNA, then translated into protein molecules, the cells building blocks.

That model seems to have left the impression that cellular protein production works analogously to an old-style factory production line: That the amount of a messenger RNA encoded by DNA on the front end translates directly into the amount of a corresponding protein produced on the back end. That idea is at the core of how gene-based cancer drug developers choose their targets.

To put that assumed congruence between RNA production and protein production to the test, the researchers examined -- in ovarian cancer cells donated by a patient -- 4,436 genes, their subsequently transcribed messenger RNA, and the resulting proteins. The assumption, that proverbial factory orders passed down the DNA-RNA line determine in a straightforward manner the amount of a protein being produced, proved incorrect 62 percent of the time.

The messenger RNA-protein connection is important because proteins are usually the targets ofgene-based cancer therapies, McDonald said. And drug developers typically measure messenger RNA levels thinking they will tell them what the proteins levels are. But the significant variations in ratios of messenger RNA to protein that the researchers found make the common method of targeting proteins via RNA seem much less than optimal.

McDonald,Mengnan Zhangand Ronghu Wu published their resultson August 15, 2017 in the journalScientific Reports. The work was funded by the Ovarian Cancer Institute, The Deborah Nash Endowment, Atlantas Northside Hospital and the National Science Foundation. The spectrophotometric technology needed to closely identify a high number of proteins is rare and costly but isavailable in Wus lab at Georgia Tech.

Whereas many studies look at normal tissue versus cancerous tissue, this new study focused on cancer progression, ormetastasis, which is what usually makes cancer deadly. The researchers looked at primary tumor tissue and also metastatic tissue.

The idea that any change in RNA level in cancerous development flows all the way up to the protein level could be leading to drug targeting errors, saidMcDonald, who heads Georgia Techs Integrated Cancer Research Center. Drug developers often look for oddly high messenger RNA levels in a cancer then go after what they believe must be the resulting oddly high levels of a corresponding protein.

Taking messenger RNA as a protein level indicator could actually work some of the time. In the McDonald teams latest experiment, in 38 percent of the cases, the rise of RNA levels in cancerous cells did indeed reflect a comparable rise of protein levels. But in the rest of cases, they did not.

So, there are going to be many instances where if youre predicting what to give therapeutically to a patient based on RNA, your prescription could easily be incorrect, McDonald said. Drug developers could be aiming at targets that arent there and also not shooting for targets that are there.

The analogy of a factory producing building materials can help illustrate what goes wrong in a cancerous cell, and also help describe the studys new insights into protein production. To complete the metaphor: The materials produced are used in the construction of the factorys own building, that is, the cells own structures.

In cancer cells, a mutation makes protein production go awry usually not by deforming proteins but by overproducing them. A lot of mutations in cancer are mutations in production levels. The proteins are being overexpressed, said McDonald, who is also aprofessor in Georgia Techs School of Biological Sciences.

A bad factory order can lead to the production of too much of a good material and then force it into the structures of the cell, distorting it. The question is: Where in the production line do bad factory orders appear?

According to the new study, the answer is less straightforward than previously thought.

The orders dont all appear on the front end of the assembly line with DNA over-transcribing messenger RNA. Additionally, some mutations that do over-transcribe messenger RNA on the front end are tamped down or canceled by regulating mechanisms further down the line, and may never end up boosting protein levels on the back end.

Regulating mechanisms also appear to be making other messenger RNA, transcribed in normal amounts, unexpectedly crank out inordinate levels of proteins.

At the heart of those regulating systems, another RNA called micro RNA may be micromanaging how much, or little, of a protein is actually produced in the end.

We have evidence that micro RNAs may be responsible for the non-correlation between the proteins and the RNA, and thats completely novel, McDonald said. Its an emerging area of research.

Micro RNA, ormiRNA, is an extremely short strand of RNA.

McDonald would like to see tissues from more cancer patients undergo similar testing. Right now, with just one patient, the data is limited, but I also really think it shows that the phenomenon is real, McDonald said.

Many past studies have looked at one particular protein and a particular gene, or a particular handful. We looked at more than 4,000, McDonald said. What that brings up is that the phenomenon is probably not isolated but instead genome-wide.

The studys authors would also like to see rarely accessible, advanced protein detecting technology become more widely available to biomolecular researchers, especially in the field of cancer drug development. Targeted gene therapy is a good idea, but you need the full knowledge of whether its affecting the protein level, McDonald said.

He pointed out that no one is at fault for the possible incompleteness of commonly held concepts about protein production.

As science progresses, it naturally illuminates new details, and formerly useful ideas need updating. With the existence of new technologies, it may be time to flesh out this particular concept for the sake of cancer research progress.

Also READ: Punching Cancer With RNA Knuckles with John McDonald

The research was supported by grants from the Ovarian Cancer Institute, The Deborah Nash Endowment Fund, Northside Hospital (Atlanta), and the National Science Foundation (CHE-452 1454501). Cancer tissues from ovary and omental sites were collected from a cancer patient at Northside Hospital with informed consent under Georgia Institute of Technology Institutional Review Board protocols (H14337). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of those agencies.

Read more:
Skewing the Aim of Targeted Cancer Therapies - Research Horizons

Gene Editing System Revamped to Target RNA Aggregates Found in Inherited ALS – ALS News Today

Researchers have found a way to break down aggregated RNA molecules that cause diseases such as certain inherited forms of amyotrophic lateral sclerosis (ALS).

As the technique has the potential to treat several diseases which currently lack treatment options, the research team from theUniversity of California, San Diego (UCSD) made sure to engineer the new system so that it could be delivered to specific tissues with non-infectious viruses.

The method builds on a well-known gene-editing system, called CRISPRCas9, but was adapted to target RNA instead of DNA. The new method is called RNA-targeting Cas9, or simply, RCas9.

This is exciting because were not only targeting the root cause of diseases for which there are no current therapies to delay progression, but weve re-engineered the CRISPR-Cas9 system in a way thats feasible to deliver it to specific tissues via a viral vector, the studys senior author, Gene Yeo, said in a press release. He is aprofessor of cellular and molecular medicine at UCSD School of Medicine.

The study, Elimination of Toxic Microsatellite Repeat Expansion RNA by RNA-Targeting Cas9, published in the journal Cell, described how the team rebuilt the Cas9 system to find and chop up disease-causing RNA molecules.

In gene editing, the CRISPRCas 9 system uses an RNA probe that matches a specific stretch of DNA. Once bound to the right gene, the Cas9 enzyme cuts the DNA, which then can be inactivated or edited. The new system targets RNA, and chops it upinstead of editing it.

RNA, whichis largely composed of similar building blocks as DNA, has numerous roles in a cell. For instance, it is used to take a copy of a gene to provide instructions for the cells protein-making machinery.

At times, however, RNA molecules start accumulating what researchers call microsatellite repeat expansions. These are stretches of repeat RNA letters that disrupt the normal activity of the RNA. When found in messenger RNAs, they prevent necessary proteins from being made.

Anabnormal sequence also makes the RNA accumulate in cells, disrupting other cell operations. This can be seen in ALS that runs in families, andin diseases such as myotonic dystrophy and Huntingtons.

In ALS, such repeats are found in the C9orf72 gene, and cause about a third of familial ALS cases, or those that run in families,according to the ALS Association.

Testing the new tool in lab-grown cells derived from ALS patients with such mutations, the team showed that RCas9 could eliminate at least 95 percent of accumulated RNA, seen as dense clusters, or foci, in the cells.

They also discovered that using RCas9 freed proteins that normally bind to RNA in cells. When abnormal RNA starts accumulating in a cell, these proteins get tied up interacting with the aggregates, instead of binding to their natural targets. Researchers said that treated patient-derived cells eventually resembled healthy cells.

For the system to be useful as a human therapy, it needs to fit into a virus the most common way to deliver gene therapy. Normal Cas9 is too large to fit into thevirus typically used. The team solved the issue by removing parts of the Cas9 enzyme required for cutting DNA, making the enzyme small enough to fit.

Yet, many more questions need to be answered before the method can be tried in patients.

The main thing we dont know yet is whether or not the viral vectors that deliver RCas9 to cells would elicit an immune response, Yeo said. Before this could be tested in humans, we would need to test it in animal models, determine potential toxicities and evaluate long-term exposure.

The group has launched a company, Locana, that will work onpreclinical-trial development of the method with the aim of bringing it to patients.

We are really excited about this work because we not only defined a new potential therapeutic mechanism for CRISPR-Cas9, we demonstrated how it could be used to treat an entire class of conditions for which there are no successful treatment options, said David Nelles, PhD, one of two lead studyauthors.

There are more than 20 genetic diseases caused by microsatellite expansions in different places in the genome. Our ability to program the RCas9 system to target different repeats, combined with low risk of off-target effects, is its major strength, added Ranjan Batra, PhD, the studys other lead author.

Original post:
Gene Editing System Revamped to Target RNA Aggregates Found in Inherited ALS - ALS News Today

Pfizer Plans Gene Therapy Manufacturing Investment in North … – BioPharm International

Pfizer is moving forward with plans to invest in a new clinical and commercial gene therapy manufacturing facility in Sanford, NC, but the work is still in the preliminary stages, said the company. A $100-million investment in the Sanford facilities is expected to create 40 jobs, according to a press release from the North Carolina governors office.

The facility will build upon a technology first developed at the University of North Carolina at Chapel Hill. Gene therapy focuses on highly specialized, one-time treatments that address the root cause of diseases caused by genetic mutation. The technology involves introducing genetic material into the body to deliver a correct copy of a gene to a patients cells to compensate for a defective or missing gene.

Gene therapy is an important area of focus for Pfizer. In 2016, the company acquired Bamboo Therapeutics, a privately held biotechnology company based in Chapel Hill focused on developing gene therapies for the potential treatment of patients with certain rare diseases related to neuromuscular conditions and those affecting the central nervous system. Pfizer also committed $4 million to support postdoctoral fellowships in North Carolina universities for training in gene therapy research, according to the press release.

A performance-based grant of $250,000 from the One North Carolina (NC) Fund will help facilitate Pfizers expansion. The One NC grant will formally be awarded to Wyeth Holdings, a wholly owned subsidiary of Pfizer. The One NC Fund provides financial assistance to local governments to help attract economic investment and to create jobs. Companies receive no money upfront and must meet job creation and capital investment targets to qualify for payment. All One NC grants require a matching grant from local governments and any award is contingent upon that condition being met.

Source: Pfizer, NC Governors Office

Read more:
Pfizer Plans Gene Therapy Manufacturing Investment in North ... - BioPharm International

MoU signed to commercialise gene therapy in India – Odisha Sun Times

New Delhi: In a bid to advance research and commercialise regenerative medicine and gene therapy in India, the Association of Biotechnology Led Enterprise (ABLE) a consortium of biotechnology companies on Friday signed a Memorandum of Understanding (MoU) with a Japan-based trade association.

The collaboration between ABLE and Forum for Innovative Regenerative Medicine (FIRM) will focus on advancing the individual and common missions by sharing information including technology, policy and laws partnerships and opportunities such as co-sponsoring meetings and other cooperation based on common concern.

It will also help advance and promote commercialisation of life saving products in regenerative medicine within India, Japan and other countries.

We are proud to be a partner in this revolutionary research and industry collaborations. The partnership is a step forward to enhance the learning and training on cell and gene treatment leading to enhancement of the cell and gene therapies which help to address major unmet medical needs in India, P. Manohar, Head (Committee for regenerative medicine group) at ABLE, said in a statement on Friday.

Our association with ABLE is an opportunity to work towards the advancement of the field (of regenerative medicine and cell and gene therapies) and tap on the potential to transform human healthcare. Through the partnership, we can share learnings and insights to contribute towards curing major human illness, added Yuzo Toda, Chairman at FIRM. (IANS)

See original here:
MoU signed to commercialise gene therapy in India - Odisha Sun Times

Americans want a say in human genome editing, survey shows – Los Angeles Times

When it comes to CRISPR, our society has some important decisions to make.

Just last week, scientists reported a new first in the journal Nature: They edited heritable cells in human embryos to treat an inherited form of heart disease. The day after the research was published, a group of genetics experts published a statement calling for further debate before applications of the technology are taken any further in humans.

According to a new survey of 1,600 adults published in the journal Science today, much of the American public shares this desire for engagement in decision-making. Led by Dietram Scheufele, a professor of science communication at the University of Wisconsin - Madison, the study found that while support for gene editing applications varies, a majority of respondents think the public should be consulted before genome editing is used in humans.

Gene editing presents the potential for remarkable benefits.

The potential to cure genetic disease and to ensure the safety of the world's food supply in the face of climate change are perhaps the most exciting opportunities, said Jennifer Doudna, a chemist at UC Berkeley who was an early pioneer of the powerful gene-editing technique CRISPR-Cas9 and was not involved in the new study.

But it also raises some serious ethical questions, especially when we turn our attention to tweaking the human genome, Scheufele said. Many people find some applications like disease treatment valuable, and others like making your children more intelligent morally shaky.

For example, scientists may eventually develop a cure for what some people dont consider an illness like a disability, Scheufele said. Would those who chose not to undergo genetic therapy or who couldnt afford it then be discriminated against even more as a result?

These and other ethical concerns go beyond the bounds of science, Scheufele says, and his poll results show that the public wants to be involved in the debate.

Oregon Health & Science University

Embryos develop into blastocysts after co-injection, which could someday be used in fertility clinics to help people trying to have children free of genetic disease.

Embryos develop into blastocysts after co-injection, which could someday be used in fertility clinics to help people trying to have children free of genetic disease. (Oregon Health & Science University)

Because of the fast-moving progress of gene editing research and the vast potential for both beneficial applications and negative consequences, many experts have called for public engagement on the issue including in a consensus report released this year by the National Academy of Sciences (NAS) and the National Academy of Medicine (NAM).

The new study strove to answer some questions emerging from the National Academies report. First, how do people feel about different applications of gene editing? And secondly, do Americans agree that the public should be consulted on gene editing applications? Similar questions had been asked in previous polls, but the authors wanted to get some more specific data.

Human genome editing can be used for two broad purposes: therapy or enhancement. Therapeutic applications include the treatment of genetic disorders like muscular dystrophy or sickle cell disease, while enhancement might be used to change your daughters eye color or make her grow taller.

Each of these changes can be heritable or not, depending on which type of cell is tweaked. Somatic cells are nonreproductive, so any changes to these cells will not be passed on to future generations. Germline cells, on the other hand, are heritable therefore, any modifications will be inherited by the treated persons children and grandchildren.

Reprinted with permission from D.A. Scheufele et al., Science 357:6351 2017

A graphic from the paper showing the acceptance of gene editing by application.

A graphic from the paper showing the acceptance of gene editing by application. (Reprinted with permission from D.A. Scheufele et al., Science 357:6351 2017)

The new poll shows that two-thirds of Americans support therapeutic applications, whether to somatic (64% support) or germline (65% support) cells. When it comes to enhancement, however, there is much less approval. Only 39% of respondents find somatic enhancement acceptable, with 35% saying it is unacceptable. Levels of support dropped even lower for heritable germline enhancement, to 26% in acceptance and 51% in opposition.

When these results were broken down by how religious respondents were, some variation emerged. Religious people are less supportive of genome editing overall. Only half of them expressed some support of treatment applications, compared with 75% of nonreligious respondents. When it comes to enhancement, 28% of religious respondents and 45% of nonreligious people reported some level of support.

The authors also ranked respondents in terms of low, medium and high knowledge by their score on a nine-question factual quiz. Those in the high-knowledge category were far more supportive of treatment applications, with 76% in support compared with only 32% of low-knowledge respondents.

When asked about enhancement applications, the high-knowledge group was very polarized, with 41% in support and a nearly equal amount in opposition. In contrast, half of low-knowledge people reported that they neither support nor oppose gene editing.

Robert Blendon, who studies health policy at the Harvard School of Public Health, said that the polarization could be there for a reason. Those who know more about the technology have probably learned about it because they have a vested interest maybe a genetic disease runs in their family or they are concerned with ethical consequences.

Reprinted with permission from D.A. Scheufele et al., Science 357:6351 2017

A graphic from the paper showing the opinions of respondents based on religiosity and knowledge.

A graphic from the paper showing the opinions of respondents based on religiosity and knowledge. (Reprinted with permission from D.A. Scheufele et al., Science 357:6351 2017)

The more religious people were, the less likely they were to trust the scientific community to responsibly develop new technologies. This trend was opposite when it came to knowledge: The more knowledgeable people were about the technology, the more likely they were to trust the scientists.

While the two groups may have very different reasons, both highly religious and highly knowledgeable people agreed that the public should be involved in decision-making before gene editing is used in humans.

Blendon said that while its clear the public wants a say in how gene editing is used, its unclear exactly what public engagement looks like. The first way most people might think of being consulted is through their elected officials, but other surveys suggest that the public actually doesnt think the government should be making decisions about genome technology.

Scheufele said that there is currently no infrastructure in place for crucial two-way communication between scientists and the public on the genome editing issue but its important to develop it.

Diverse groups and perspectives have an important role to play in shaping the early stages of human genome editing research, Scheufele said. Scientists may not think to investigate all the questions that the public may deem vital.

If we ask the wrong questions, he said, then we may have perfect technical answers to all the wrong questions.

mira.abed@latimes.com

@mirakatherine

See the original post here:
Americans want a say in human genome editing, survey shows - Los Angeles Times

Skin transplants could treat diabetes and obesity – Futurity: Research News

Skin transplantation could be an effective way to deliver gene therapy to treat type 2 diabetes and obesity, new research in mice suggests.

The technique could enable a wide range of gene-based therapies to treat many human diseases.

We think this can provide a long-term safe option for the treatment of many diseases

We resolved some technical hurdles and designed a mouse-to-mouse skin transplantation model in animals with intact immune systems, says study author Xiaoyang Wu, assistant professor in the cancer research department at the University of Chicago.

We think this platform has the potential to lead to safe and durable gene therapy in mice and, we hope, in humans, using selected and modified cells from skin.

Beginning in the 1970s, physicians learned how to harvest skin stem cells from a patient with extensive burn wounds, grow them in the laboratory, then apply the lab-grown tissue to close and protect a patients wounds. This approach is now standard. However, the application of skin transplants is better developed in humans than in mice.

The mouse system is less mature, Wu says. It took us a few years to optimize our 3D skin organoid culture system.

This study is the first to show that an engineered skin graft can survive long term in wild-type mice with intact immune systems.

We have a better than 80 percent success rate with skin transplantation, Wu says. This is exciting for us.

The researchers focused on diabetes because it is a common non-skin disease that can be treated by the strategic delivery of specific proteins.

They inserted the gene for glucagon-like peptide 1 (GLP1), a hormone that stimulates the pancreas to secrete insulin. This extra insulin removes excessive glucose from the bloodstream, preventing the complications of diabetes. GLP1 can also delay gastric emptying and reduce appetite.

Using CRISPR, a tool for precise genetic engineering, they modified the GLP1 gene. They inserted one mutation, designed to extend the hormones half-life in the blood stream, and fused the modified gene to an antibody fragment so that it would circulate in the blood stream longer. They also attached an inducible promoter, which enabled them to turn on the gene to make more GLP1, as needed, by exposing it to the antibiotic doxycycline. Then they inserted the gene into skin cells and grew those cells in culture.

When these cultured cells were exposed to an air/liquid interface in the laboratory, they stratified, generating what the authors referred to as a multi-layered, skin-like organoid.

Next, they grafted this lab-grown gene-altered skin onto mice with intact immune systems. There was no significant rejection of the transplanted skin grafts.

When the mice ate food containing minute amounts of doxycycline, they released dose-dependent levels of GLP1 into the blood. This promptly increased blood-insulin levels and reduced blood-glucose levels.

When the researchers fed normal or gene-altered mice a high-fat diet, both groups rapidly gained weight. They became obese. When normal and gene-altered mice got the high-fat diet along with varying levels of doxycycline, to induce GLP1 release, the normal mice grew fat and mice expressing GLP1 showed less weight gain.

Expression of GLP1 also lowered glucose levels and reduced insulin resistance.

Together, our data strongly suggest that cutaneous gene therapy with inducible expression of GLP1 can be used for the treatment and prevention of diet-induced obesity and pathologies, the authors write.

When they transplanted gene-altered human cells to mice with a limited immune system, they saw the same effect. These results, the authors wrote, suggest that cutaneous gene therapy for GLP1 secretion could be practical and clinically relevant.

This approach, combining precise genome editing in vitro with effective application of engineered cells in vivo, could provide significant benefits for the treatment of many human diseases, the authors note.

We think this can provide a long-term safe option for the treatment of many diseases, Wu says. It could be used to deliver therapeutic proteins, replacing missing proteins for people with a genetic defect, such as hemophilia. Or it could function as a metabolic sink, removing various toxins.

Skin progenitor cells have several unique advantages that are a perfect fit for gene therapy. Human skin is the largest and most accessible organ in the body. It is easy to monitor. Transplanted skin can be quickly removed if necessary. Skins cells rapidly proliferate in culture and can be easily transplanted. The procedure is safe, minimally invasive, and inexpensive.

There is also a need. More than 100 million US adults have either diabetes (30.3 million) or prediabetes (84.1 million), according the Centers for Disease Control and Prevention. More than two out of three adults are overweight. More than one out of three are considered obese.

Additional authors of the study are from the University of Chicago and the University of Illinois at Chicago. The National Institutes of Health, the American Cancer Society, and the V Foundation funded the study.

Source: University of Chicago

Follow this link:
Skin transplants could treat diabetes and obesity - Futurity: Research News

Drugmakers’ hopes for gene therapy rise despite tiny sales in Europe – Reuters

LONDON (Reuters) - The science of gene therapy is finally delivering on its potential, and drugmakers are now hoping to produce commercially viable medicines after tiny sales for the first two such treatments in Europe.

Thanks to advances in delivering genes to targeted cells, more treatments based on fixing faulty DNA in patients are coming soon, including the first ones in the United States.

Yet the lack of sales for the two drugs already launched to treat ultra-rare diseases in Europe highlights the hurdles ahead for drugmakers in marketing new, extremely expensive products for genetic diseases.

After decades of frustrations, firms believe there are now major opportunities for gene therapy in treating inherited conditions such as haemophilia. They argue that therapies offering one-off cures for intractable diseases will save health providers large sums in the long term over conventional treatments which each patient may need for years.

In the past five years, European regulators have approved two gene therapies - the first of their kind in the world, outside China - but only three patients have so far been treated commercially.

UniQure's (QURE.O) Glybera, for a very rare blood disorder, is now being taken off the market given lack of demand.

The future of GlaxoSmithKline's (GSK.L) Strimvelis for ADA-SCID - or "bubble boy" disease, where sufferers are highly vulnerable to infections - is uncertain after the company decided to review and possibly sell its rare diseases unit.

Glybera, costing around $1 million per patient, has been used just once since approval in 2012. Strimvelis, at about $700,000, has seen two sales since its approval in May 2016, with two more patients due to be treated later this year.

"It's disappointing that so few patients have received gene therapy in Europe," said KPMG chief medical adviser Hilary Thomas. "It shows the business challenges and the problems faced by publicly-funded healthcare systems in dealing with a very expensive one-off treatment."

These first two therapies are for exceptionally rare conditions - GSK estimates there are only 15 new cases of ADA-SCID in Europe each year - but both drugs are expected to pave the way for bigger products.

The idea of using engineered viruses to deliver healthy genes has fuelled experiments since the 1990s. Progress was derailed by a patient death and cancer cases, but now scientists have learnt how to make viral delivery safer and more efficient.

Spark Therapeutics (ONCE.O) hopes to win U.S. approval in January 2018 for a gene therapy to cure a rare inherited form of blindness, while Novartis (NOVN.S) could get a U.S. go-ahead as early as next month for its gene-modified cell therapy against leukaemia - a variation on standard gene therapy.

At the same time, academic research is advancing by leaps and bounds, with last week's successful use of CRISPR-Cas9 gene editing to correct a defect in a human embryo pointing to more innovative therapies down the line.

Spark Chief Executive Jeffrey Marrazzo thinks there are specific reasons why Europe's first gene therapies have sold poorly, reflecting complex reimbursement systems, Glybera's patchy clinical trials record and the fact Strimvelis is given at only one clinic in Italy.

He expects Spark will do better. It plans to have treatment centers in each country to address a type of blindness affecting about 6,000 people around the world.

Marrazzo admits, however, there are many questions about how his firm should be rewarded for the $400 million it has spent developing the drug, given that healthcare systems are geared to paying for drugs monthly rather than facing a huge upfront bill.

A one-time cure, even at $1 million, could still save money over the long term by reducing the need for expensive care, in much the same way that a kidney transplant can save hundreds of thousands of dollars in dialysis costs.

But gene therapy companies - which also include Bluebird Bio (BLUE.O), BioMarin (BMRN.O), Sangamo (SGMO.O) and GenSight (SIGHT.PA) - may need new business models.

One option would be a pay-for-performance system, where governments or insurers would make payments to companies that could be halted if the drug stopped working.

"In an area like haemophilia I think that approach is going to make a ton of sense, since the budget impact there starts to get more significant," Marrazzo said.

Haemophilia, a hereditary condition affecting more than 100,000 people in markets where specialty drugmakers typically operate, promises to be the first really big commercial opportunity. It offers to free patients from regular infusions of blood-clotting factors that can cost up to $400,000 a year.

Significantly, despite its move away from ultra-rare diseases, GSK is still looking to use its gene therapy platform to develop treatments for more common diseases, including cancer and beta-thalassaemia, another inherited blood disorder.

Rivals such as Pfizer (PFE.N) and Sanofi (SASY.PA) are also investing, and overall financing for gene and gene-modified cell therapies reached $1 billion in the first quarter of 2017, according to the Alliance of Regenerative Medicine.

Shire (SHP.L) CEO Flemming Ornskov - who has a large conventional haemophilia business and is also chasing Biomarin and Spark in hunting a cure for the bleeding disorder - sees both the opportunities and the difficulties of gene therapy.

"Is it something that I think will take market share mid- to long-term if the data continues to be encouraging? Yes. But I think everybody will have to figure out a business model."

Reporting by Ben Hirschler; editing by David Stamp

Read this article:
Drugmakers' hopes for gene therapy rise despite tiny sales in Europe - Reuters

UCSD team adapts CRISPR to edit RNA for disease therapies – The San Diego Union-Tribune

UC San Diego researchers have invented a technology that offers a possible new way to fight genetic diseases, and have built a San Diego biotech company around their discovery.

The scientists adapted the powerful CRISPR/Cas9 DNA editing system, which has transformed the world of biology, to work on RNA, the messenger molecule that carries DNAs instructions into cells.

The system worked in cell cultures to stop production of RNA involved in forms of myotonic dystrophy, ALS and in Huntingtons disease. These are all incurable genetic diseases that can be fatal. This RNA can be toxic in itself, or produce abnormal proteins that cause disease.

About 95 percent of the disease-causing RNA was destroyed in the cell cultures.

The scientists have formed a San Diego biotech company called Locana to bring the technology to patients. Several years of development, including animal testing, is expected before that can happen.

The study was published Thursday in the journal Cell. Go to j.mp/rnacrispr to get the study. Gene Yeo was the senior author. The first authors were David Nelles and Ranjan Batra, postdoctoral researchers in Yeos lab.

CRISPR/Cas9 cuts DNA at specified targets, inactivating or altering gene sequences. It has been used for such feats like editing the genome of human embryos. The adapted system doesnt target the genome, but only RNA.

Scientists led by UC San Diegos Gene Yeo modified CRISPR so it doesnt target DNA and instead attacks specific RNA sequences, while leaving others alone. This specificity is vital for therapeutic purposes. It is delivered by an adenovirus, a virus commonly used in gene therapy.

The study expands on previous research that showed the RNA-adapted CRISPR could track RNA as it moves around cells. It didnt affect RNA production, however.

That study included Jennifer Doudna, a UC Berkeley scientist who helped pioneer the CRISPR system. Doudna is on Locanas scientific advisory board, Yeo said. He and Nelles are co-founders of Locana.

The Cas9 component, a protein that destroys the target, was too large to be delivered by the virus. So the team cut the proteins size by removing unnecessary parts used to cleave DNA. The result, RCas9, is guided by an accompanying RNA molecule to the target site.

Yeo said he expects the viral delivery system will remain effective for perhaps five to 10 years. Thats important because RNA is continually being produced from DNA, so the new disease-causing RNA must likewise be destroyed.

CRISPR star Jennifer Doudna calls for public debate on embryo editing

With embryo gene editing a reality, humanity enters a new era

Gene editing used to find cancer's genetic weak spots

DARPA funds UC gene drive research against mosquito-borne diseases

Can geneticists engineer healthier humans?

UCSD gene drive technology offers life-transforming power

bradley.fikes@sduniontribune.com

(619) 293-1020

Read the rest here:
UCSD team adapts CRISPR to edit RNA for disease therapies - The San Diego Union-Tribune

Silverstein-backed startup will test gene therapy for Parkinson’s – FierceBiotech

Regenxbio has joined forces with investment firm OrbiMed and a new nonprofit foundation to create Prevail Therapeutics, a startup focused on new biologics and gene therapiesfor Parkinson's disease (PD).

Prevail will draw on the expertise of the Silverstein Foundation for Parkinson's with GBA, which concentrates on a particular form of the disease caused by mutations in the glucocerebrosidase gene.

The foundation was set up this year by OrbiMed's co-head of private equity Jonathan Silverstein, who was diagnosed with GBA-linked PD in February and is mobilizing efforts to discover a cure for the disease. Silverstein backed the foundation with $10 million of his own money, and is intent on accelerating research into PD with GBA as well as other forms of the disease.

Prevail says it will focus initially on research coming out of the lab of its co-founder and CEO Asa Abeliovich, M.D., Ph.D., who is on the faculty of Columbia University as well as being a scientific adviser to the Silverstein Foundation and co-founder of neurodegenerative disease biotech Alector.

By joining forces with Regenxbio, Prevail launches with an exclusive license to the gene therapy specialist's adeno-associated virus (AAV) based vector technology NAV AAV9 for PD and other neurodegenerative disorders.

Silverstein said that the NAV platform and Dr. Abeliovich's "deep expertise in the molecular mechanisms of neurodegeneration provides us with a promising opportunity to develop potential life-changing therapies for patients suffering from Parkinson's disease and other neurodegenerative diseases."

He told CNBC today that Prevail's board will also have some big names, including Leonard Bell, co-founder and former CEO of Alexion, OrbiMed venture partner and Alexion co-founder Steve Squinto and serial entrepreneur Peter Thompson of Silverback Therapeutics and Corvus Pharmaceuticals.

The new company will initially focus on GBA1, the most common of the PD mutations, which is estimated to be present in up to 10% of U.S. PD patients and perhaps 100,000 people worldwide. The disease mechanism linked to the mutationan accumulation of alpha-synuclein in the brainmay have implications for the broader PD population and other neurodegenerative diseases.

"Many of the drugs we are trying for Parkinson's with GBA may work in the broader Parkinson's population," said Silverstein. The aim will be to get drugs approved for use in GBA patients first, and then expand their use into other patient groups.

The work of the foundation is attracting investment from companies who are not even active in PD, with cancer specialist Celgene today pledging a grant of $5 million.

Read more from the original source:
Silverstein-backed startup will test gene therapy for Parkinson's - FierceBiotech

Pfizer chooses Sanford, North Carolina site for $100m gene therapy plant – BioPharma-Reporter.com

Pfizer has chosen a site in Sanford, North Carolina for a gene therapy production plant, just 40 miles from its recent acquisition Bamboo Therapeutics Inc.

The US drug firm had been search for a site since March.

According to North Carolina Governor Roy Cooper, Pfizer will spend $100m (85m) on the new facility and has also committed $4m to support postdoctoral fellowships in North Carolina universities for training in gene therapy research.

The project will create jobs that deliver a total payroll impact of more than $3.9m each year to the community according to the North Carolina Department of Commerce and the Economic Development Partnership.

The project will be part funded by a $250,000 grant previously awarded to Wyeth which was acquired by Pfizer in 2009 - by the One North Carolina Fund, which helps local Governments attract economic investment.

Bamboo buy

The decision follows a little over a year after the US drug manufacturer acquired Bamboo Therapeutics, a North Carolina-based gene therapy developer.

The deal included a recombinant Adeno-Associated Virus (rAAV) vector design and production technology, a Phase I candidate for Giant Axonal Neuropathy and a preclinical programme targeting Duchenne Muscular Dystrophy (DMD).

Pfizer also gained a 11,000sq ft gene therapy manufacturing facility in Chapel Hill that Bamboo bought from the University of North Carolina in 2016.

See more here:
Pfizer chooses Sanford, North Carolina site for $100m gene therapy plant - BioPharma-Reporter.com

Pfizer investing $100M in Sanford plant expansion, adding jobs … – Triangle Business Journal


Triangle Business Journal
Pfizer investing $100M in Sanford plant expansion, adding jobs ...
Triangle Business Journal
Pfizer has confirmed plans to invest $100 million in the expansion of its Sanford research and manufacturing plant.

and more »

Follow this link:
Pfizer investing $100M in Sanford plant expansion, adding jobs ... - Triangle Business Journal

Pfizer to invest $100M in Sanford gene therapy operation, add jobs … – WRAL Tech Wire

Updated Aug. 8, 2017 at 7:02 a.m.

Published: 2017-08-07 16:07:00 Updated: 2017-08-08 07:02:05

Sanford, N.C. Pharmaceutical giant Pfizer Inc. plans to invest $100 million in its Sanford operations as part of a push into gene therapy, officials said Monday.

The effort builds on a technology developed at the University of North Carolina at Chapel Hill and will create 40 jobs in Sanford.

"Pfizer is proud to further expand our presence in North Carolina, particularly as we build our leadership in gene therapy," Lynn Bottone, site leader at Pfizer Sanford, said in a statement. "We look forward to the next phase of this expansion as we build a clinical and commercial manufacturing facility."

Preliminary work on the expansion and initial hiring have already begun. The 230-acre campus employs about 450 people, reports the N.C. Biotechnology Center.

Gene therapy is a potentially transformational technology for patients that involves highly specialized, one-time treatments to address the root cause of diseases caused by genetic mutation. The technology involves introducing genetic material into the body to deliver a correct copy of a gene to a patients cells to compensate for a defective or missing gene.

Last year, Pfizer acquired Bamboo Therapeutics Inc., a privately held biotechnology company in Chapel Hill focused on developing gene therapies for the potential treatment of patients with certain rare diseases related to neuromuscular conditions and those affecting the central nervous system. Pfizer also committed $4 million to support postdoctoral fellowships in North Carolina universities for training in gene therapy research.

"We are excited that Carolinas research will improve lives and create jobs for North Carolinians," UNC-Chapel Hill Chancellor Carol Folt said in a statement. "This is a perfect example of how placing innovation at the center of our university creates new opportunities. We are proud to be a part of the technologies, expertise and infrastructure that went into Bamboo Therapeutics and helped make this manufacturing expansion in Sanford possible. Gene therapy is a strength at Carolina, and we look forward to continue to help advance this industry."

Pfizer is also expanding a drug-manufacturing facility in Rocky Mount that it acquired from Hospira in 2015. The $190 million project will add 65,000 square feet of sterile injectable facilities but will not create any new jobs. The plant employs about 300 people.

Gov. Roy Cooper visited Pfizers Sanford facility last week to take a tour and meet with the companys senior leaders.

"North Carolina is one of the few places in the country with the biotech resources to take an idea all the way from the lab to the manufacturing line," Cooper said in a statement. "Pfizers investment in Lee County is a prime example of how North Carolinas world-class universities and cutting-edge industries work together to move our state forward."

Pfizer qualified for a performance-based grant of $250,000 from the One North Carolina Fund, which provides state assistance matched by local governments to help attract economic investment and create jobs. Companies receive no money upfront and must meet job and investment targets to obtain payment.

WRAL TechWire any time: Twitter, Facebook

Read more from the original source:
Pfizer to invest $100M in Sanford gene therapy operation, add jobs ... - WRAL Tech Wire

Pfizer Inc. Expands Biopharmaceutical Research Center in Sanford, North Carolina – Area Development Online

Related ResearchPfizer Inc., one of the worlds premier biopharmaceutical companies, will expand its research-production facilities in Sanford, North Carolina. The company will prepare to produce new gene therapy medicines.

Governor Roy Cooper announced the company plans to invest $100 million in its research facility in Lee County, creating 40 jobs and building upon a technology first developed at the University of North Carolina at Chapel Hill.

The Pfizer expansion in Sanford will focus on gene therapy, a potentially transformational technology for patients, focused on highly specialized, one-time treatments that address the root cause of diseases caused by genetic mutation. The technology involves introducing genetic material into the body to deliver a correct copy of a gene to a patients cells to compensate for a defective or missing gene.

Pfizer is proud to further expand our presence in North Carolina, particularly as we build our leadership in gene therapy, states Lynn Bottone, Site Leader at Pfizer Sanford. We look forward to the next phase of this expansion as we build a clinical and commercial manufacturing facility.

As an incentive a performance-based grant of $250,000 from the One North Carolina Fund will help facilitate Pfizers expansion in Lee County. The One NC grant will formally be awarded to Wyeth Holdings, LLC, a wholly-owned subsidiary of Pfizer Inc.

The One NC Fund provides financial assistance to local governments to help attract economic investment and to create jobs. Companies receive no money upfront and must meet job creation and capital investment targets to qualify for payment. All One NC grants require a matching grant from local governments and any award is contingent upon that condition being met.

North Carolina is one of the few places in the country with the biotech resources to take an idea all the way from the lab to the manufacturing line, Governor Cooper said. Pfizers investment in Lee County is a prime example of how North Carolinas world-class universities and cutting-edge industries work together to move our state forward.

In 2016, the company acquired Bamboo Therapeutics, Inc., a privately held biotechnology company based in Chapel Hill focused on developing gene therapies for the potential treatment of patients with certain rare diseases related to neuromuscular conditions and those affecting the central nervous system. Pfizer also committed $4 million to support postdoctoral fellowships in North Carolina universities for training in gene therapy research.

Innovation drives economic opportunity and expansion, said North Carolina Commerce Secretary Anthony M. Copeland. Pfizers decision to expand in North Carolina proves how our investments in education pay off in new jobs and new solutions to the worlds toughest challenges.

We are excited that Carolinas research will improve lives and create jobs for North Carolinians, said Carol Folt, Chancellor of the University of North Carolina at Chapel Hill. This is a perfect example of how placing innovation at the center of our university creates new opportunities. We are proud to be a part of the technologies, expertise and infrastructure that went into Bamboo Therapeutics and helped make this manufacturing expansion in Sanford possible. Gene therapy is a strength at Carolina and we look forward to continue to help advance this industry.

The North Carolina Department of Commerce and the Economic Development Partnership of N.C. (EDPNC) were instrumental in supporting the companys investment decision. In addition to North Carolina Commerce and the Economic Partnership of North Carolina, other key partners in the project include the North Carolina General Assembly, the North Carolina Community College System, the University of North Carolina at Chapel Hill, the North Carolina Biotechnology Center, Duke Energy, Lee County, and the Sanford Area Growth Alliance.

Go here to see the original:
Pfizer Inc. Expands Biopharmaceutical Research Center in Sanford, North Carolina - Area Development Online

Gene Therapy Is Now Available, but Who Will Pay for It? – Scientific American

By Ben Hirschler

LONDON (Reuters) - The science of gene therapy is finally delivering on its potential, and drugmakers are now hoping to produce commercially viable medicines after tiny sales for the first two such treatments in Europe.

Thanks to advances in delivering genes to targeted cells, more treatments based on fixing faulty DNA in patients are coming soon, including the first ones in the United States.

Yet the lack of sales for the two drugs already launched to treat ultra-rare diseases in Europe highlights the hurdles ahead for drugmakers in marketing new, extremely expensive products for genetic diseases.

After decades of frustrations, firms believe there are now major opportunities for gene therapy in treating inherited conditions such as haemophilia. They argue that therapies offering one-off cures for intractable diseases will save health providers large sums in the long term over conventional treatments which each patient may need for years.

In the past five years, European regulators have approved two gene therapies - the first of their kind in the world, outside China - but only three patients have so far been treated commercially.

UniQure's Glybera, for a very rare blood disorder, is now being taken off the market given lack of demand.

The future of GlaxoSmithKline's Strimvelis for ADA-SCID - or "bubble boy" disease, where sufferers are highly vulnerable to infections - is uncertain after the company decided to review and possibly sell its rare diseases unit.

Glybera, costing around $1 million per patient, has been used just once since approval in 2012. Strimvelis, at about $700,000, has seen two sales since its approval in May 2016, with two more patients due to be treated later this year.

"It's disappointing that so few patients have received gene therapy in Europe," said KPMG chief medical adviser Hilary Thomas. "It shows the business challenges and the problems faced by publicly-funded healthcare systems in dealing with a very expensive one-off treatment."

These first two therapies are for exceptionally rare conditions - GSK estimates there are only 15 new cases of ADA-SCID in Europe each year - but both drugs are expected to pave the way for bigger products.

The idea of using engineered viruses to deliver healthy genes has fuelled experiments since the 1990s. Progress was derailed by a patient death and cancer cases, but now scientists have learnt how to make viral delivery safer and more efficient.

Spark Therapeutics hopes to win U.S. approval in January 2018 for a gene therapy to cure a rare inherited form of blindness, while Novartis could get a U.S. go-ahead as early as next month for its gene-modified cell therapy against leukaemia - a variation on standard gene therapy.

At the same time, academic research is advancing by leaps and bounds, with last week's successful use of CRISPR-Cas9 gene editing to correct a defect in a human embryo pointing to more innovative therapies down the line.

Spark Chief Executive Jeffrey Marrazzo thinks there are specific reasons why Europe's first gene therapies have sold poorly, reflecting complex reimbursement systems, Glybera's patchy clinical trials record and the fact Strimvelis is given at only one clinic in Italy.

He expects Spark will do better. It plans to have treatment centers in each country to address a type of blindness affecting about 6,000 people around the world.

Marrazzo admits, however, there are many questions about how his firm should be rewarded for the $400 million it has spent developing the drug, given that healthcare systems are geared to paying for drugs monthly rather than facing a huge upfront bill.

A one-time cure, even at $1 million, could still save money over the long term by reducing the need for expensive care, in much the same way that a kidney transplant can save hundreds of thousands of dollars in dialysis costs.

But gene therapy companies - which also include Bluebird Bio, BioMarin, Sangamo and GenSight - may need new business models.

One option would be a pay-for-performance system, where governments or insurers would make payments to companies that could be halted if the drug stopped working.

"In an area like haemophilia I think that approach is going to make a ton of sense, since the budget impact there starts to get more significant," Marrazzo said.

Haemophilia, a hereditary condition affecting more than 100,000 people in markets where specialty drugmakers typically operate, promises to be the first really big commercial opportunity. It offers to free patients from regular infusions of blood-clotting factors that can cost up to $400,000 a year.

Significantly, despite its move away from ultra-rare diseases, GSK is still looking to use its gene therapy platform to develop treatments for more common diseases, including cancer and beta-thalassaemia, another inherited blood disorder.

Rivals such as Pfizer and Sanofi are also investing, and overall financing for gene and gene-modified cell therapies reached $1 billion in the first quarter of 2017, according to the Alliance of Regenerative Medicine.

Shire CEO Flemming Ornskov - who has a large conventional haemophilia business and is also chasing Biomarin and Spark in hunting a cure for the bleeding disorder - sees both the opportunities and the difficulties of gene therapy.

"Is it something that I think will take market share mid- to long-term if the data continues to be encouraging? Yes. But I think everybody will have to figure out a business model."

More here:
Gene Therapy Is Now Available, but Who Will Pay for It? - Scientific American

Archives