Scientists one step closer to finding cure for HIV after successfully eliminating the virus from infected mice
Results show that the treatment to suppress HIV replication and gene editing therapy, when given sequentially, can eliminate HIV from cells and organs of infected animals
In a first, scientists claim to have eliminated HIV from the DNA of infected mice, which could be a critical and promising step toward the development of a possible cure for millions of people infected with the virus. Calling it a "groundbreaking" discovery, the research team says their results show that it is possible to produce a cure for HIV infection.
"Data provides proof-of-concept that permanent viral elimination is possible," states the paper. The method used by the team is now being tested in primates, and the team hopes to move to clinical trials on human patients in 2020, which will be subject to approval by the Food and Drug Administration (FDA).
According to UNAIDS, 36.9 million people globally were living with HIV in 2017, even as 940,000 people died from AIDS-related illnesses in 2017. Current HIV treatment focuses on the use of antiretroviral therapy (ART). While ART suppresses HIV replication, it does not eliminate the virus from the body. Therefore, ART is not a cure for HIV, and it requires life-long use.
If it is stopped, HIV rebounds, renewing replication and fueling the development of AIDS. UNAIDS estimates show that 77.3 million people have become infected with HIV since the start of the epidemic, even as 35.4 million people have died from AIDS-related illnesses since the start of the epidemic.
The findings state that the HIV rebound is directly attributed to the ability of the virus to "integrate its DNA sequence into the genomes of cells of the immune system", where it lies dormant and beyond the reach of antiretroviral drugs. In the new study — a collaborative effort between researchers at the Lewis Katz School of Medicine at Temple University and the University of Nebraska Medical Center (UNMC) — the team used a combination of gene editing tool CRISPR and a recently developed therapeutic strategy known as long-acting slow-effective release or LASER ART to eliminate HIV from the genomes of living animals, thus curing them of the virus. The team included virologists, immunologists, molecular biologists, pharmacologists, and pharmaceutical experts.
In their previous work, the research team used CRISPR-Cas9 technology to develop a novel gene editing and gene therapy delivery system aimed at removing HIV DNA from genomes that harbor the virus. Similar to ART, however, gene editing cannot totally eliminate HIV on its own. Accordingly, for the new study, the researchers combined their gene editing system with LASER ART.
"LASER ART targets viral sanctuaries and maintains HIV replication at low levels for extended periods of time, reducing the frequency of ART administration. The long-lasting medications were made possible by pharmacological changes in the chemical structure of the antiretroviral drugs. The modified drug was packaged into nanocrystals, which readily distribute to tissues where HIV is likely to be lying dormant. From there, the nanocrystals, stored within cells for weeks, slowly release the drug,” share the researchers in their findings.
The researchers also wanted to see whether LASER ART could suppress HIV replication long enough for CRISPR-Cas9 to completely rid cells of viral DNA.
For their experiment, the research team used mice engineered to produce human T cells that are susceptible to HIV infection. Once the infection was established, mice were treated with LASER ART and subsequently with CRISPR-Cas9. At the end of the treatment, the analysis showed a total elimination of HIV in one-third of the infected mice.
The study — Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice — was published on July 2 in Nature Communications.