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CRISPR cuts HIV: potential preventive and therapeutic strategy
Researchers have exploited the clustered regularly interspaced short palindromic repeats (CRISPR) system, used by bacteria to protect themselves against viruses, to help human cells resist and fight against HIV infection. The study is published today in the journal Nature Communications. It comes from a research team based in the Salk Institute in California, the Iowa State University and the University of Tsukuba in Japan, led by Prof Juan Carlos Izpisua Belmonte, of Salk's Gene Expression Laboratory.

CRISPR works along with CRISPR-associated genes (Cas) to create site-specific double-stranded breaks in DNA of hostile viruses.  Prof Izpisua Belmonte said "Evolution has led to some of the most astonishing mechanisms for protecting organisms against their natural pathogens. Understanding the immune responses by which bacteria protect themselves against viral infections has allowed us to engineer novel platforms for the targeting of devastating viruses, such as HIV, in human patients."

In the current study, the research team adapted the CRISPR/Cas9 system to human cells to try to develop a strategy to overcome the issue of latent HIV infection. CRISPR uses guide RNAs to dictate the location of the DNA cuts. The researchers developed guide RNAs specific to unique spots on the HIV virus and added CRISPR, the guide RNAs and other necessary molecules to immune cells that had been infected with HIV. The results indicated that that CRISPR successfully cut and inactivated the virus, resulting in complete virus removal from up to 72% of cells. Importantly, the CRISPR could disrupt latently integrated viral genome. The authors suggested that their system would provide ‘long-term adaptive defence against new viral infection, expression and replication in human cells’. The work extended previous studies showing that CRISPR was active against shortened, inactive forms of HIV to show that it was effective against full-length, active HIV and could, as first author  Hsin-Kai (Ken) Liao of the Izpisua Belmonte lab pointed out, “actually excise the virus out of the human genome."

The researchers also tested whether CRISPR would have a prophylactic effect by adding it to human cells prior to HIV infection. The results showed that CRISPR targeted copies of the virus before they began to replicate, preventing infection. Prof Izpisua Belmonte commented: "The main advantage of this technology is not only that viral DNA integrated into the human genome can be eliminated but perhaps, most importantly, the prophylactic application. By eliminating the virus at the early steps of its life cycle, we can altogether prevent the infection of human cells in an analogous manner to how conventional vaccines work."

The team engineered human induced pluripotent stem cells that stably expressed HIV-targeted CRISPR/Cas9 and showed that they could be differentiated into different types of HIV reservoir cells, all with HIV resistance. However, further research is required into how the technology could be used in human patients. It is also vital to determine whether rapid HIV evolution will lead to escape from CRISPR. With that in mind, the team is studying the effectiveness of adding more guiding RNAs to the CRISPR mix, allowing recognition of a greater range of cut sites. "The HIV virus can mutate very quickly," said Liao. "If we target multiple regions at the same time, we reduce the chance that the virus can develop resistance." The research continues into this promising new anti-viral therapeutic strategy.

Liao H-K, Gu Y, Diaz A, Marlett J,                Takahashi Y, Li M, Suzuki K, Xu R, Hishida T, Chang C-J, Rodriguez Esteban C, Young J, Izpisua Belmonte JC. Use of the CRISPR/Cas9 system as an intracellular defense against HIV-1 infection in human cells. Nature Communications (2015) 6, Article number: 6413 doi:10.1038/ncomms7413

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I think world should pay more attention to cure of AIDS. I understand research takes time but it has taken such a huge time already. So many general people, politicians, and celebrities with HIV die every year and we can save them if we find a cure for it.
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