\"During acute infection, HIV actively replicates,\" explained co-senior study investigator Kamel Khalili, Ph.D., professor and chair of the department of neuroscience at LKSOM. \"With EcoHIV mice, we were able to investigate the ability of the CRISPR\/Cas9 strategy to block viral replication and potentially prevent systemic infection.\" The excision efficiency of their strategy reached 96% in EcoHIV mice, providing the first evidence for HIV-1 eradication by prophylactic treatment with a CRISPR\/Cas9 system. <\/p>\n
In the third animal model, a latent HIV-1 infection was recapitulated in humanized mice engrafted with human immune cells, including T cells, followed by HIV-1 infection. \"These animals carry latent HIV in the genomes of human T cells, where the virus can escape detection, Dr. Hu explained. Amazingly, after a single treatment with CRISPR\/Cas9, viral fragments were successfully excised from latently infected human cells embedded in mouse tissues and organs. <\/p>\n
In all three animal models, the researchers employed a recombinant adeno-associated viral (rAAV) vector delivery system based on a subtype known as AAV-DJ\/8. \"The AAV-DJ\/8 subtype combines multiple serotypes, giving us a broader range of cell targets for the delivery of our CRISPR\/Cas9 system,\" remarked Dr. Hu. Additionally, the researchers re-engineered their previous gene-editing apparatus to now carry a set of four guide RNAs, all designed to efficiently excise integrated HIV-1 DNA from the host cell genome and avoid potential HIV-1 mutational escape. <\/p>\n
To determine the success of the strategy, the team measured levels of HIV-1 RNA and used a novel and cleverly designed live bioluminescence imaging system. \"The imaging system, developed by Dr. Won-Bin Young while at the University of Pittsburgh, pinpoints the spatial and temporal location of HIV-1-infected cells in the body, allowing us to observe HIV-1 replication in real time and to essentially see HIV-1 reservoirs in latently infected cells and tissues,\" stated Dr. Khalili. <\/p>\n
The researchers were excited by their findings and are optimistic about their next steps. 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 cells,\" Dr. Khalili concluded. \"Our eventual goal is a clinical trial in human patients.\" <\/p>\n
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More: \"During acute infection, HIV actively replicates,\" explained co-senior study investigator Kamel Khalili, Ph.D., professor and chair of the department of neuroscience at LKSOM. \"With EcoHIV mice, we were able to investigate the ability of the CRISPR\/Cas9 strategy to block viral replication and potentially prevent systemic infection.\" The excision efficiency of their strategy reached 96% in EcoHIV mice, providing the first evidence for HIV-1 eradication by prophylactic treatment with a CRISPR\/Cas9 system. Continue reading
\nCRISPR Eliminates HIV in Live Animals - Genetic Engineering & Biotechnology News<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"