Details

Autor(en) / Beteiligte

• Mancuso, Pietro
• Chen, Chen
• Kaminski, Rafal
• Gordon, Jennifer
• Liao, Shuren
• Robinson, Jake A.
• Smith, Mandy D.
• Liu, Hong
• Sariyer, Ilker K.
• Sariyer, Rahsan
• Peterson, Tiffany A.
• Donadoni, Martina
• Williams, Jaclyn B.
• Siddiqui, Summer
• Bunnell, Bruce A.
• Ling, Binhua
• MacLean, Andrew G.
• Burdo, Tricia H.
• Khalili, Kamel

Titel

CRISPR based editing of SIV proviral DNA in ART treated non-human primates

Ist Teil von

• Nature communications, 2020-11, Vol.11 (1), p.6065-11, Article 6065

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2020

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Elimination of HIV DNA from infected individuals remains a challenge in medicine. Here, we demonstrate that intravenous inoculation of SIV-infected macaques, a well-accepted non-human primate model of HIV infection, with adeno-associated virus 9 (AAV9)-CRISPR/Cas9 gene editing construct designed for eliminating proviral SIV DNA, leads to broad distribution of editing molecules and precise cleavage and removal of fragments of the integrated proviral DNA from the genome of infected blood cells and tissues known to be viral reservoirs including lymph nodes, spleen, bone marrow, and brain among others. Accordingly, AAV9-CRISPR treatment results in a reduction in the percent of proviral DNA in blood and tissues. These proof-of-concept observations offer a promising step toward the elimination of HIV reservoirs in the clinic. Removal of integrated HIV DNA remains a roadblock for HIV cure. Here, Mancuso et al . show that intravenous administration of an adeno-associated virus-based CRISPR/Cas9 gene editing construct to SIV-infected macaques results in excision of integrated proviral DNA from infected blood cells and tissues known to be viral reservoirs.