Nature communications · 2020
Gene editing and elimination of latent herpes simplex virus in vivo.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Aubert Martine, Strongin Daniel E, Roychoudhury Pavitra, Loprieno Michelle A, Haick Anoria K, Klouser Lindsay M, Stensland Laurence, Huang Meei-Li, Makhsous Negar, Tait Alexander, De Silva Feelixge Harshana S, Galetto Roman, Duchateau Philippe, Greninger Alexander L, Stone Daniel, Jerome Keith R
Аннотация
We evaluate gene editing of HSV in a well-established mouse model, using adeno-associated virus (AAV)-delivered meganucleases, as a potentially curative approach to treat latent HSV infection. Here we show that AAV-delivered meganucleases, but not CRISPR/Cas9, mediate highly efficient gene editing of HSV, eliminating over 90% of latent virus from superior cervical ganglia. Single-cell RNA sequencing demonstrates that both HSV and individual AAV serotypes are non-randomly distributed among neuronal subsets in ganglia, implying that improved delivery to all neuronal subsets may lead to even more complete elimination of HSV. As predicted, delivery of meganucleases using a triple AAV serotype combination results in the greatest decrease in ganglionic HSV loads. The levels of HSV elimination observed in these studies, if translated to humans, would likely significantly reduce HSV reactivation, shedding, and lesions. Further optimization of meganuclease delivery and activity is likely possible, and may offer a pathway to a cure for HSV infection.