15 March 2022

And the sediment remained

HIV gene therapy: what are scientists thinking about?

Tatiana Ten, Life4me+

Scientists have high hopes for developments in the field of HIV gene therapy. Currently, CRISPR-Cas9 technology is considered one of the most promising strategies — a kind of "genetic scissors" that allow you to remove viral genes from the cell structure.

Previous studies have shown that CRISPR effectively cuts out not only the genes of hereditary diseases from cells, but also the integrated human immunodeficiency virus (HIV 1).

Scientists from the University of Pisa (Italy) decided to find out — where does the cut-out DNA of the virus go?

Dr. Michele Lai, one of the authors of the study, believes that the cut-out viral DNA molecules form stable rings that can integrate into the genome. That is, they can form small infectious molecules. This fact may become a problem in the work on CRISPR technology in the treatment of HIV.

To test this idea, Lai and his colleagues treated HIV-infected cells with CRISPR and used a method of specific amplification of ring viral DNA. This allowed them to detect tiny plasmids in cells treated with CRISPR, capable of resuming the development of infection.

"We did some calculations, and it turned out that for every 1000 cells there is about one such cell. Even if CRISPR works in 100% of T cells, you will still have a sufficient number of cells in which [plasmids] can trigger infection," said Mauro Pistello, senior author of a paper published in the Journal of Virology (Lai et al. CRISPR/Cas9 Ablation of Integrated HIV-1 Accumulates Proviral DNA Circles with Reformed Long Terminal Repeats). 

Further experiments confirmed this theory — even after successful removal of the virus with the help of gene therapy, "it can assemble into something functional."

Experts believe that such a course of events is "the most provocative scenario." But, since such a risk exists, the process needs to be studied in detail during further research. This will create a "functional and safe strategy for gene therapy in the future."

"The idea of a multi—purpose strategy to combat HIV using gene therapy now has two levels of support: curbing the evolution of viral resistance and eliminating the possibility of reassembling the virus into a functional molecule," the scientists say.

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