Historic 1st: DOCTORS COMPLETELY REMOVE HIV FROM MICE

 
scientist working in lab with DNA structure on a laptop screen
 
 
 

The first treatment is a long-acting slow-effective release (LASER) form of anti retro viral therapy.

The second treatment involves the removal of viral DNA using a gene editing tool called CRISPR-Cas9.

In a recent Nature Communications paper, the researchers describe how they tested the two-step approach in a mouse model of human HIV.

Of the mice that received LASER ant iretro viral therapy followed by gene editing, the “virus was eliminated from cell and tissue reservoirs in up to a third of infected animals,” note the authors.

In contrast, treating mice with either LASER anti retro viral therapy or gene editing — but not both — “resulted in viral rebound in 100% of treated infected animals.”

 

“The big message of this work,” says co-senior study author Kamel Khalili, Ph.D., of the Lewis Katz School of Medicine (LKSOM) at Temple University in Philadelphia, PA, “is that it takes both CRISPR-Cas9 and virus suppression through a method such as LASER [antiretroviral therapy], administered together, to produce a cure for HIV infection.”

Khalili is a professor in LKSOM’s department of neuroscience and its chair. He is also the director of LKSOM’s Center for Neuro virology and of its Comprehensive Neuro AIDS Center.

HIV can hide in a dormant state

According to the most recent figures from UN AIDS, worldwide, 36.9 million people were living with HIV in 2017. In the same year, around 1.8 million contracted the virus.

People with HIV who do not receive treatment have a high risk of developing AIDS, an advanced state of immune system damage. People with AIDS typically survive for no longer than 3 years without treatment.

 

HIV attacks CD4, or T helper, cells, which are a type of white blood cell that helps regulate immune responses to infection.

The virus fuses with the T helper cell, takes over its DNA, and forces the cell to make copies of HIV. When the copies are ready, the cell releases them into the bloodstream, from which point they can go on to infect more cells and start the process over again.

Anti retro viral therapy can halt, not kill, HIV

Anti retro viral therapy is a combination of drugs that stop the progress of HIV by targeting different stages of the virus’s life cycle.

Many people with HIV who receive anti retro viral therapy and adhere to their treatment regimen can expect to live a long life in good health. However, anti retro viral therapy does not rid the body of HIV, so people have to keep taking the drugs to prevent the development of AIDS.

If a person stops anti retro viral therapy, HIV can flare up again and continue its life cycle. This is because the virus inserts its genetic material into the genomes of the immune cells that it infects. This ability allows HIV to hide quietly in a place that anti retro viral therapy cannot reach.

In a 2017 study, Prof. Khalili and team described how they used CRISPR-Cas9 gene editing to remove HIV genetic material from the DNA of infected cells to massively reduce viral load. However, like anti retro viral therapy, gene editing by itself does not completely remove all traces of HIV.

 

Their new study describes how LASER anti retr oviral therapy targets HIV in its “viral sanctuaries” and drip feeds it with drugs that suppress the virus’s ability to replicate.

LASER therapy buys time for gene editing

LASER anti retro viral therapy differs from conventional anti retro viral therapy in that its drugs have a different chemistry, require fewer doses, and last longer.

LASER anti retro viral therapy drugs take the form of nano crystals that can quickly make their way into tissues harboring dormant HIV. Once inside HIV-affected cells, the nano crystals can slowly release their payload over several weeks.

Prof. Khalili explains that the purpose of the new study was “to see whether LASER [anti retro viral therapy] could suppress HIV replication long enough for CRISPR-Cas9 to completely rid cells of viral DNA.”

They tested the approach in mice with human T cells that could easily contract HIV and in which the virus became dormant following interrupted anti retro viral therapy treatment.

The team treated the mice with LASER anti retro viral therapy followed by CRISPR-Cas9 and then examined their HIV viral load. Various tests detected no trace of HIV DNA in around one-third of the animals.

“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,” Prof. Khalili concludes.

We now have a clear path to move ahead to trials in nonhuman primates and possibly clinical trials in human patients within the year.”

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