![]() ![]() Researchers have found that these ancient inactive viruses are missing several genetic elements that HIV contains. “The concept is exciting and it makes sense: We want to accelerate what evolution has already achieved with thousands of relatives of HIV previously defeated and buried in every human cells.” “Armed with this knowledge, and inspired by these natural defenses, we will combine our expertise to that of other HOPE participants to engineer new repressive molecules that can target HIV and lock it permanently,” Feschotte said. His team’s goal is to identify the precise molecules (proteins) used by our own cells to lock endogenous retroviruses. Unlike HIV, however, they are no longer capable of infection because they are disabled and permanently silenced. “The central concept behind strategy is inspired by the way our cells naturally cope with the remnants of ancient retroviruses that have integrated into our genetic material during evolution,” said Cedric Feschotte, one of the investigators of the HOPE Collaboratory and professor of molecular biology and genetics at Cornell’s College of Agriculture and Life Sciences.įeschotte’s lab studies the biology of these so-called endogenous retroviruses, which make up 8% of our DNA. However, unlike HIV, the ancient viruses remain in a silenced state or are defective. ![]() HIV also integrates into the genome of a person living with HIV. The inspiration for the “block and lock” part of their strategy comes from ancient viruses that have integrated themselves into the human genome over millions of years of evolution. The researchers involved in the HOPE Collaboratory are calling their new, alternative tactic “block-lock-excise,” and it targets latent HIV in new ways, without reactivating it. And even a small remaining reservoir of latent virus means that someone living with HIV must remain on daily treatments. Most attempts at curing HIV have centered around purposefully reactivating the latent virus in order to flush it out with antiretroviral therapy – an approach called “shock and kill.” But researchers have struggled to reactivate every copy of the virus in the body or, at least, to do so without severe undesirable side effects. Moreover, a lapse in this daily therapy can lead to a rapid rebound of the infection. HIV is notorious for its ability to hide in a latent state in immune cells while latent viruses don’t cause overt symptoms or full-blown AIDS, they can lead to long-term health complications for those living with HIV and can’t be targeted with standard antiretroviral therapy. The HOPE Collaboratory is one of 10 groups awarded a five-year grant under the Martin Delaney Collaboratories program, the flagship program on HIV cure research at the NIH. ![]() “I think it’s extremely important for us to explore a broad range of scientific approaches to find the best cure for people living with HIV, as quickly as we can.” Melanie Ott, director of the Gladstone Institute of Virology, and the program director and a principal investigator of the HOPE Collaboratory. “This is a fundamentally different approach to targeting HIV than what everyone else has been trying,” said Dr. Their approach, which aims to both silence and permanently remove HIV from the body, takes advantage of knowledge about how other viruses have become naturally inactivated over time. The group, known as the HIV Obstruction by Programmed Epigenetics (HOPE) Collaboratory, will be led by researchers at Gladstone Institutes, Scripps Research and Weill Cornell Medicine, and will include investigators on the Ithaca campus. Now, with a $26.5 million grant from the National Institutes of Health (NIH), a multidisciplinary group of researchers from institutions around the world is trying a completely new strategy for curing HIV. ![]() But attempts to completely eliminate the virus from the bodies of people living with HIV, curing them for good, have failed. Over the last 40 years, HIV has shifted from a deadly and mysterious virus to one that can be controlled with daily drugs. ![]()
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