CRISPR: A hope to treat HIV
Scientist have eliminated HIV in mice using a genome editing method called CRISPR.
CRISPR (Clustered regularly interspaced short palindromic repeats) is a way by bacteria to fight the invasion of a foreign DNA molecules. Scientist have developed a way to use this system to perform gene editing with a scissor like precision and since Human Immunodeficiency Virus resides in the host’s DNA, CRISPR can be a great method to fight HIV. What this technique does is that by using guiding molecules called gRNAs that have the complimentary sequence to the one that scientists are looking for, a protein called Cas9 cuts those sequences and binds the other two sides of the cut site.
When a patient gets infected by HIV, the virus inserts itself into the patient’s DNA and controls the patient’s cell replication mechanism to replicate itself. HIV primarily infects CD4+ T cells, which leads to AIDS (acquired immunodeficiency syndrome). Anti-retroviral medications stop the replication of viruses but do not remove them from patient’s cells and all this means although current generation of HIV drugs control its progress, they are not the actual cure and thus, the threat of the re-emergence of virus is always there.
— Retrieved from https://techcrunch.com/2017/05/03/scientists-have-eliminated-hiv-in-mice-using-crispr/
Based on a research by Chaoran Yin et al., after treating HIV infected mice with CRISPR/Cas9, they could see that the infection was removed almost completely (96%) from the organs and tissue of the mice. Although researchers are really excited by their success, there are still many challenges left ahead. Research has shown that HIV mutates; which means changes some of its molecules and this way escapes the precision system of CIRSPR. This can be alleviated by using multiple guiding molecules to find those mutated molecules as well.
CRISPR has shown to affect the surrounding areas where it makes a cut by leaving off-target changes. These off-target deletions or additions might turn off existing genes in the area or lead to the mutations of HIV RNAs that are no longer detectable by the CRISPR gRNAs. So, the efficiency must be improved in a way that leaves not enough HIV left in the host to replicate again and at the same time reduce the offtarget changes to the minimum. Additionally, moving from animal studies to primates and after that to clinical trials in humans is not an easy task.
There have been many papers during the past few years that tried to use CRISPR to fight HIV. However, CRISPR can be applied to other life threatening diseases too. Based on a research by two teams at Broad Institute, through a RNA amplification method combined with CRISPR, even the presence of Zika viral RNA or the distinctive RNA of cancer cells could be detected.
Health system and pharma companies are moving towards a personalized medicine therapy and this means in the near future, Genome editing techniques like CRISPR/Cas9 can detect and edit trouble making genes in humans like cancer genes while not making any off-target risks to the patient.
References:
Yin, C., Zhang, T., Qu, X., Zhang, Y., Putatunda, R., Xiao, X., … Hu, W. (2017). In Vivo Excision of HIV-1 Provirus by saCas9 and Multiplex Single-Guide RNAs in Animal Models. Molecular Therapy, 25(5), 1168– 1186.
