Gene editing eradicates HIV-1

CRISPR More than three decades after the discovery of HIV, AIDS remains a major public health problem affecting greater than 35.3 million people worldwide. Current antiretroviral therapy fails to eradicate HIV infection, partly due to the persistence of virus reservoirs. A new paper just published shows that RNA-guided HIV-1 genome cleavage by Cas9 CRISPR technology has shown promising efficacy in disrupting the HIV-1 genome in latently infected cells, suppressing virus gene expression and replication, and immunizing uninfected cells against HIV-1 infection. These properties may provide a viable path toward a permanent cure for AIDS, and provide a means to vaccinate against other pathogenic viruses. Given the ease and rapidity of Cas9/guide RNA development, personalized therapies for individual patients with HIV-1 variants might be developed quickly.

Comment: In spite of the breezy optimism of this paper (and this is progress), the work described has only been carried out on cultured cells in vitro. It is not clear whether or how easily it will be to replicate this finding in animals, and we’re still along way away from clinical trials which will be needed to show if this approach works in HIV-infected people.


RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection. PNAS USA July 21, 2014, doi: 10.1073/pnas.1405186111
AIDS remains incurable due to the permanent integration of HIV-1 into the host genome, imparting risk of viral reactivation even after antiretroviral therapy. New strategies are needed to ablate the viral genome from latently infected cells, because current methods are too inefficient and prone to adverse off-target effects. To eliminate the integrated HIV-1 genome, we used the Cas9/guide RNA (gRNA) system, in single and multiplex configurations. We identified highly specific targets within the HIV-1 LTR U3 region that were efficiently edited by Cas9/gRNA, inactivating viral gene expression and replication in latently infected microglial, promonocytic, and T cells. Cas9/gRNAs caused neither genotoxicity nor off-target editing to the host cells, and completely excised a 9,709-bp fragment of integrated proviral DNA that spanned from its 5′ to 3′ LTRs. Furthermore, the presence of multiplex gRNAs within Cas9-expressing cells prevented HIV-1 infection. Our results suggest that Cas9/gRNA can be engineered to provide a specific, efficacious prophylactic and therapeutic approach against AIDS.

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