Genome editing tool – CRISPR eliminates HIV infection in mice.

By Kavish Khatib

Researchers have developed and demonstrated the successful removal of HIV-1 provirus from mice organs and tissue completely. By using a gene-editing technique called CRISPR (clustered regularly interspaced short palindromic repeats). This ground-breaking technique is a tremendous advancement in the cure of HIV infection.

The research team, led by investigators at the Lewis Katz School of Medicine at Temple University and the University of Pittsburgh showed that it is possible to excise HIV DNA from the genomes of living animals to eliminate further infection. However, they admitted that practical problems need to be overcome. The main issue is to efficiently deliver the CRSIPR genome to the target genome. Nonetheless, their work is a huge step forward towards carrying out clinical trials of the technique on humans.


‘ – the main issue is to efficiently deliver the CRSIPR genome to the target genome’


The applied method involves using CRISPR-associated protein 9 (Cas9) to mediate the genome editing. Essentially, a single guide RNA is loaded with the enzyme Cas9 and this complex is injected and it finds any DNA complementary to the single guide RNA and cleaves it. Moreover, an extra DNA sequence is then inserted in the hopes that it may recombine in the same spot that was just cleaved – thereby swapping the gene directly.

The CRISPR-associated protein 9 (Cas9) is an RNA-guided mechanism was first discovered in 2005. It is an RNA-guided endonuclease originally discovered as part of the bacterial adaptive immunity. It is used as resistance to foreign genetic elements and plays a key role in a bacterial defence system.


mice

Schematic process of CRISPR/Cas excising the HIV DNA in mice


The current treatment for HIV infection is a combined antiretroviral therapy (cART). Which is a cocktail of drugs which suppresses the virus from different aspects. A huge drawbacks of the current treatment is that due to the high mutation rate of the virus sooner or later some of the medication will have a lower effect on the virus. But, at this moment in time, many cART drugs have been developed and are being combined to combat the viral mutation rate. So many diagnosed HIV-infected patients can have a long longevity.


‘A huge drawbacks of the current treatment that due to the high mutation rate of the virus sooner or later some of the medication will have a lower affect on the virus.’


However, a permanent cure is still lacking due to the existence of latent reservoirs, in which HIV proviral DNA integrates into the host genome. Upon cART cessation, the HIV viral load rebounds to cause a catastrophic resurgence of HIV/AIDS. Thus, several promising and novel strategies are being developed to achieve a permanent or “sterile” cure for HIV/AIDS.

The research team have admitted, this is not a permanent solution and it’s still early days for the crew — the study merely builds on a previous proof-of-concept study they conducted last year and the technique has only been used on mice so far. But, should the scientists be able to replicate their findings, the technique could move to human trials in the future.


‘The latest WHO figures from 2016 show that 18.2 Million people are suffering from AIDS and only 46% are receiving retroviral therapy.’


A statement made by the co-author Dr Khalili: “The next stage would be to repeat the study in primates, a more suitable animal model where HIV infection induces disease, in order to further demonstrate the elimination of HIV-1 DNA in latently infected T cells and other sanctuary sites for HIV-1, including brain cell”. The eventual goal is a clinical trial in human patients.

This is a highly promising technique to help combat the fight against AIDS. The latest WHO figures from 2016 show that 18.2 Million people are suffering from AIDS and only 46% are receiving retroviral therapy. A permanent cure would pave the path to alleviate the countless of lives that are in threat.

Bibliography


http://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(17)30110-7?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1525001617301107%3Fshowall%3Dtrue

http://mashable.com/2017/05/03/scientists-crispr-hiv-infection-mice/#fI1ub8JfUiqQ

http://www.who.int/hiv/data/en/

 Image sources:

http://www.sciencephoto.com/media/253984/view

https://techcrunch.com/2017/05/03/scientists-have-eliminated-hiv-in-mice-using-crispr/

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