Details

Autor(en) / Beteiligte

• Burdo, Tricia H
• Chen, Chen
• Kaminski, Rafal
• Sariyer, Ilker K
• Mancuso, Pietro
• Donadoni, Martina
• Smith, Mandy D
• Sariyer, Rahsan
• Caocci, Maurizio
• Liao, Shuren
• Liu, Hong
• Huo, Wenwen
• Zhao, Huaqing
• Misamore, John
• Lewis, Mark G
• Simonyan, Vahan
• Thompson, Elaine E
• Xu, Ethan Y
• Cradick, Thomas J
• Gordon, Jennifer
• Khalili, Kamel

Titel

Preclinical safety and biodistribution of CRISPR targeting SIV in non-human primates

Ist Teil von

• Gene therapy, 2024-05, Vol.31 (5-6), p.224-233

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• In this study, we demonstrate the safety and utility of CRISPR-Cas9 gene editing technology for in vivo editing of proviral DNA in ART-treated, virally controlled simian immunodeficiency virus (SIV) infected rhesus macaques, an established model for HIV infection. EBT-001 is an AAV9-based vector delivering SaCas9 and dual guide RNAs designed to target multiple regions of the SIV genome: the viral LTRs, and the Gag gene. The results presented here demonstrate that a single IV inoculation of EBT-001 at each of 3 dose levels (1.4 × 10 , 1.4 × 10 and 1.4 × 10 genome copies/kg) resulted in broad and functional biodistribution of AAV9-EBT-001 to known tissue reservoirs of SIV. No off-target effects or abnormal pathology were observed, and animals returned to their normal body weight after receiving EBT-001. Importantly, the macaques that received the 2 highest doses of EBT-001 showed improved absolute lymphocyte counts as compared to antiretroviral-treated controls. Taken together, these results demonstrate safety, biodistribution, and in vivo proviral DNA editing following IV administration of EBT-001, supporting the further development of CRISPR-based gene editing as a potential therapeutic approach for HIV in humans.