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

Date

2020-11-27

Authors

Mancuso, Pietro
Chen, Chen
Kaminski, Rafal
Gordon, Jennifer
Liao, Shuren
Robinson, Jake A.
Smith, Mandy D.
Liu, Hong
Sariyer, Ilker K.
Sariyer, Rahsan

ORCID

0000-0001-6196-3722 (Bunnell, Bruce A.)

Journal Title

Journal ISSN

Volume Title

Publisher

Springer Nature

Abstract

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.

Description

Citation

Mancuso, P., Chen, C., Kaminski, R., Gordon, J., Liao, S., Robinson, J. A., Smith, M. D., Liu, H., Sariyer, I. K., Sariyer, R., Peterson, T. A., Donadoni, M., Williams, J. B., Siddiqui, S., Bunnell, B. A., Ling, B., MacLean, A. G., Burdo, T. H., & Khalili, K. (2020). CRISPR based editing of SIV proviral DNA in ART treated non-human primates. Nature communications, 11(1), 6065. https://doi.org/10.1038/s41467-020-19821-7

Rights

© The Author(s) 2020

License

Attribution 4.0 International (CC BY 4.0)