CRISPR prospects for HIV treatment

13 March 2015

New research using ‘cellular scissors’ gets one step closer to producing a drug which could potentially prevent and treat human immunodeficiency virus (HIV). 

The scientists adapted the powerful bacterial defence technology known as CRISPR/Cas9 to target HIV inside human cells. The CRISPR/Cas9 system is used by bacteria to cut up foreign DNA at specific regions dictated by guide RNAs

Scientists have already used CRISPR/Cas9, and the older zinc finger nuclease method, to edit genes, but the Salk Institute team were interested in its defensive potential. They used CRISPR/Cas9 to target and disrupt the HIV lifecycle within human cells. Senior author, Juan Carlos Izpisua Belmonte said: “Understanding the immune responses by which bacteria protect themselves against viral infections have allowed us to engineer novel platforms for the targeting of devastating viruses, such as HIV, in human patients”.  

Existing HIV treatment uses combinations of drugs to suppress active infection whilst reducing the chances of drug resistance developing. The drugs target individual steps of the HIV virus lifecycle; for instance, some stop affected cells producing more viruses. Significantly, the treatments do not remove copies of the virus that are hidden within the DNA of human cells, and if the treatment is stopped then active growth of the virus can rapidly resume. 

The researchers developed guide RNAs to bind to unique spots on the HIV viral genome. Adding these RNA, CRISPR and other molecules needed for the system to work to immune cells that had been infected with HIV, they found CRISPR cut the right spots in HIV’s genes, inactivating the virus. The virus was removed in 72% of cells. Further, CRISPR cut up HIV that was hidden and dormant within the cells’ DNA. 

Importantly, the researchers showed that the CRISPR/Cas9 works before and after the virus is embedded in the host cell genome. The study also showed for the first time the method is effective against active, full length HIV rather than the shortened, inactive version of the virus. 

Further, the team found the system could potentially prevent an infection. When they added CRISPR/ Cas9 to human cells before they became infected with HIV the system prevented an infection by chopping up copies of the virus before they could start replicating.

Going forward, more research is needed to determine how the technology could be used in human patients. The team are already starting to explore the issue of HIV evolving to escape CRISPR by looking at the effectiveness of adding more guiding RNAs to the mix. First author of the research paper, Hsin-Kai (Ken) Liao said: “If we target multiple regions at the same time, we reduce the chance that the virus can develop resistance”.

Meanwhile the US Food and Drug Administration (FDA) have granted approval for further clinical trials for an HIV therapy that involves a genome editing technique to modify the gene that produces one of the cell surface molecules HIV uses to get inside white blood cells. Another similar technique has also been granted approval for clinical trials.

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