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Scientists eliminate HIV from animal’s genome for the first time; indicate possible cure for HIV

Current HIV treatment focuses on the use of antiretroviral therapy (ART). ART suppresses HIV replication but does not eliminate the virus from the body. Therefore, ART is not a cure for HIV, and it requires life-long use.

By: Lifestyle Desk | New Delhi | Published: July 3, 2019 5:11:45 pm
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For the first time, researchers have eliminated replication-competent HIV-1 DNA — the virus responsible for AIDS — from the genomes of living animals.

The study, published in the journal Nature Communications, marks a critical step toward the development of a possible cure for humans infected with HIV. Most HIV-positive individuals can live their entire life without progressing to AIDS, although it requires a cocktail of different medications that interrupt viral replication.

“Our study shows that treatment to suppress HIV replication and gene editing therapy, when given sequentially, can eliminate HIV from cells and organs of infected animals,” said Kamel Khalili, director of the center for neurovirology and the Comprehensive NeuroAIDS Center at Temple University’s Lewis Katz School of Medicine, who is one of the study’s lead authors.

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Current HIV treatment focuses on the use of antiretroviral therapy (ART) which suppresses HIV replication but does not eliminate the virus from the body. Therefore, ART is not a cure for HIV, and needs to be taken life-long. If it is stopped, HIV rebounds, renewing replication and fuelling the development of AIDS.

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 ART drugs.

In previous work, Dr Khalili’s team used CRISPR-Cas9 technology to develop a novel gene editing and gene therapy delivery system aimed at removing HIV DNA from genomes harbouring the virus. In rats and mice, they showed that the gene editing system could effectively excise large fragments of HIV DNA from infected cells, significantly impacting viral gene expression. However, gene editing also cannot completely eliminate HIV on its own.

For the new study, Dr Khalili and colleagues combined their gene editing system with a recently developed therapeutic strategy known as long-acting slow-effective release (LASER) ART. LASER ART was co-developed by Dr Howard Gendelman and Benson Edagwa, PhD, assistant professor of pharmacology at UNMC.

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.

According to Dr Khalili, “We wanted to see whether LASER ART could suppress HIV replication long enough for CRISPR-Cas9 to completely rid cells of viral DNA.”

“The big message of this work is that it takes both CRISPR-Cas9 and virus suppression through a method such as LASER ART, administered together, to produce a cure for HIV infection,” Dr Khalili said. “We now have a clear path to move ahead to trials in non-human primates and possibly clinical trials in human patients within the year.”

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