For more than 20 years, HIV/AIDS patients have widely been treated with the “AIDS Cocktail”, also known as combined antiretroviral therapy (cART). And although this combination therapy has given individuals infected with HIV a considerably improved quality of life and a significantly extended life expectancy, it requires patients to undergo ongoing and costly treatment to suppress HIV-1 replication and does not actually possess curative properties. As such, if HIV patients cease cART, the previously latent viral load rebounds almost immediately and ultimately causes a remarkable resurgence of the HIV/AIDS virus and related symptoms.


However, in a recent study, “In Vivo Excision of HIV-1 Provirus by saCas9 and Multiplex Single-Guide RNAs in Animal Models”, as published in Molecular Therapy, Yin et al demonstrate the “feasibility and efficiency of excising the HIV-1 provirus in three different animal models [including a humanized mouse model] using an all-in-one adeno-associated virus (AAV) vector to deliver multiplex single-guide RNAs (sgRNAs) plus Staphylococcus aureus Cas9 (saCas9).” Specifically, successful proviral excision was detected by PCR genotyping in the spleen, lungs, heart, colon and brain in humanized bone marrow/liver/thymus (BLT) mice with chronic HIV-1 infection, after a single injection of quadraplex sgRNAs/saCas9 AAV-DJ/8.


But this should not be viewed as a magical CRISPER-based cure for HIV. There are still some significant obstacles, including gene delivery in vivo, to overcome before human clinical trials are feasible. “In vivo genome editing efficiency relies mainly on effective gene delivery. Lentivirus-mediated Cas9/gRNA delivery has been preferentially and extensively employed in most laboratories; however, safety and immunogenicity concerns limit its clinical applications,” according to Yin et al. Preclinical research indicates that splitting Cas9 into functional N-terminal and C-terminal parts may provide a new way to more effectively deliver Cas9 in murine models and gives increasing hope to the future of gene therapies in the treatment of HIV/AIDS in humans.


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