How CRISPR gene-editing tech can fight HIV – SFGate

Posted: October 23, 2017 at 11:46 am

Photo: LOREN ELLIOTT, Special To The Chronicle

A heat map illustrates how effectively mutated cells blocked HIV, in a UCSF lab.

A heat map illustrates how effectively mutated cells blocked HIV, in a UCSF lab.

How CRISPR gene-editing tech can fight HIV

Researchers at UCSF have received a three-year, $1.6 million grant to advance their work using novel gene-editing technology to make human blood cells less susceptible to HIV infection.

The grant, from biopharmaceutical giant Gilead Sciences, a global leader in sales of HIV treatments, will fund a team of scientists working to modify the DNA of a type of white blood cell to make them immune to HIV infection.

The cells, called T cells, have long been a focus of researchers seeking to improve HIV treatments. T cells help the immune system fight many diseases, including some cancers and flu viruses. They play a unique role in HIV because the virus targets and destroys T cells, and HIV-positive patients whose T cells become too depleted by the virus will progress to AIDS.

Using a gene-editing technique known as CRISPR, the UCSF researchers have already tested dozens of genes believed to play a role in how HIV spreads within the body. They do this by collecting blood samples from HIV-negative patients, altering the DNA of those cells, and then introducing the HIV virus to the modified cells in test tubes. Within two weeks, they can see whether the change to the gene has eliminated the cells ability to become infected with HIV.

CRISPR can be used to modify the DNA of plants, animals and other living organisms. It is considered a groundbreaking method because it is simpler and cheaper than other gene-editing techniques.

This is connecting CRISPR to HIV and opening up whole new avenues of research in understanding the interplay between human genetics and HIV, said Alex Marson, an assistant professor of microbiology and immunology at UCSF who leads the lab that received the Gilead grant.

The grant, announced this week, will allow Marsons lab to pursue an ambitious goal of uncovering why HIV remains dormant in some cells, only to awaken unpredictably, sometimes years later. Known as HIV latency, this characteristic of the virus is why HIV-positive patients must take antiretroviral drugs which are only effective in attacking the awake HIV for life.

The tricky thing about HIV, and one reason its so hard to cure, is that it can hide in the DNA of the human cells, said Joe Hiatt, a doctoral student of medicine and philosophy in Marsons lab and a leader in the research initiative. It becomes DNA and integrates into your DNA.

The problem has perplexed researchers for years. But Marson and Hiatt see potential for using CRISPR to discover which genes control HIV latency. They hope to use the gene-editing tool to create latent HIV cells in test tubes, and then modify the DNA in those cells to see which edits may coax the HIV out of hiding and make it susceptible to drugs. This will be the most challenging and complicated part of the research. If done successfully, it could lead to the development of drugs that target latent HIV and perhaps cure HIV permanently.

CRISPR technology is potentially revolutionary because HIV is a type of virus that will sneak its own genetic code into the genetic code of the human cell, said Ross Wilson, a scientist at UC Berkeleys Innovative Genomics Institute who is not involved in the grant. Its like hiding a book in a stack at the library, and the book has instructions to build a nasty bomb. To get rid of that information, you need to get it back out of the library. Weve never had the technology to do that inside the living cell until CRISPR came along. Its the first efficient way to do that inside living cells.

It is the first research initiative that Foster Citys Gilead, through its philanthropic program, has funded that involves using CRISPR as a tool in HIV cure-related research. While $1.6 million is not a huge amount, it comes with fewer restrictions than many government grants. The grant will fund a team of five researchers for three years.

It is one of five grants totaling $7.5 million, announced this week, that Gilead has awarded research institutions for HIV and AIDS-related initiatives. The others are to the University of Massachusetts Medical School; Dana-Farber Cancer Institute; Institute of Human Genetics, French National Center for Scientific Research and University of Montpellier; and Frederick National Laboratory for Cancer Research, AIDS and Cancer Virus Program.

A Gilead spokesman said that if the UCSF researchers discover how latent HIV can be targeted by drugs, the company will not necessarily have rights to licensing agreements or other commercial benefits. The grant is from the companys philanthropy program and is meant to support HIV research independent of Gileads business interests, he said.

Catherine Ho is a San Francisco Chronicle staff writer. Email: cho@sfchronicle.com Twitter: @Cat_Ho

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How CRISPR gene-editing tech can fight HIV - SFGate

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