“Knocking out” genes in cells of people living with HIV could lead to new methods of treatment, say scientists
Targeting the human genes that HIV takes over and uses to replicate could provide a new approach to HIV treatment and suppression – although more research is required.
A potential new way of treating HIV could target five human genes, three of which were previously unknown, which act as hosts of the virus inside the body and are not necessary for cell survival, according to a group of scientists in the USA.Researchers say the genes inside CD4+ cells – the human cells which the virus uses to replicate – could be disrupted without interfering with cell survival, creating new possibilities for suppressing HIV.
The team, from the Ragon Institute and the Broad Institute, used a cutting-edge molecular tool, called CRISPR, which allows genomes to be edited through changing parts of their DNA sequence.
Two previously-known genes, the HIV co-receptors CD4 and CCR5, were also picked out by CRISPR, an impressively versatile new system capable of targeting and knocking out more than 18,500 genes at DNA level. Using other techniques, previous research had identified hundreds of other host dependency factors, but without the CRISPR technology, study results yielded large discrepancies and could not be verified.
The system uses two molecules to introduce a mutation into the DNA which the cell recognises and tries to repair – allowing scientists to observe the cell’s response. It has already proved instrumental in other studies pursuing a cure for HIV, including a laboratory dish study which also targeted HIV-infected cells in March 2016.
Ryan J Park, one of the authors of the report, believes the findings could help to reduce the ability of the virus to build resistance by leading to a greater diversity of antiretroviral drugs.
“Because HIV mutates so rapidly, drug-resistant strains frequently emerge – particularly when patients miss doses of their medication,” he said, warning that further studies would be required to explore the toxicity of targeted gene therapy, which he called a “challenging” and “potentially costly” approach.
“Current anti-HIV medications overwhelmingly target viral proteins. Developing new drugs to target human genes required for HIV infection is a promising approach, with potentially fewer opportunities for the development of resistance.”
ARVs currently interfere with the replication process used by the virus to insert its code into CD4 cells.
“Viruses commandeer human genes to make essential building blocks for their replication,” said Bruce Walker, the director of the Ragon Institute and a co-corresponding author of the paper.
“Viruses are very small and have very few genes – HIV has only nine, while humans have more than 19,000.”
The findings also highlighted factors in host cells which are vital to the development of viruses but can be removed without critically damaging the cell.
“Our goal was to identify human genes that are absolutely essential for HIV to replicate but could be eliminated without harming a human patient.”
The paper, ‘A genome-wide CRISPR screen identifies a restricted set of HIV host dependency factors’, is published in Nature Genetics.