Multiplexed Simian Immunodeficiency Virus-Specific Paired RNA-Guided Cas9 Nickases Inactivate Proviral DNA-Reference-Cited by-同舟云学术

Multiplexed Simian Immunodeficiency Virus-Specific Paired RNA-Guided Cas9 Nickases Inactivate Proviral DNA

Published:2021-11-09 Issue:23 Volume:95 Page:
ISSN:0022-538X
Container-title:Journal of Virology
language:en
Short-container-title:J Virol

Author:

Smith Lisa M.¹²,Ladner Jason T.³,Hodara Vida L.¹,Parodi Laura M.¹,Harris R. Alan⁴⁵,Callery Jessica E.¹,Lai Zhao⁶⁷,Zou Yi⁷,Raveedran Muthuswamy⁴⁵,Rogers Jeffrey⁴⁵,Giavedoni Luis D.¹^ORCID

Affiliation:

1. Host-Pathogen Interactions Program and Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas, USA

2. Department of Microbiology, Immunology, and Molecular Genetics, UT Health San Antonio, San Antonio, Texas, USA

3. The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, Arizona, USA

4. Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA

5. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA

6. Department of Molecular Medicine, UT Health San Antonio, San Antonio, Texas, USA

7. Greehey Children’s Cancer Research Institute, UT Health San Antonio, San Antonio, Texas, USA

Abstract

Our approach to HIV cure, utilizing the translatable SIV/rhesus macaque model system, aims at provirus inactivation and its removal with the least possible off-target side effects. We developed single molecules that delivered either three truncated SIV-specific gRNAs along with Cas9 nuclease or three pairs of SIV-specific gRNAs (six individual gRNAs) along with Cas9 nickase to enhance efficacy of on-target mutagenesis.

Funder

HHS | NIH | National Center for Advancing Translational Sciences

HHS | National Institutes of Health

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

Link

https://journals.asm.org/doi/pdf/10.1128/JVI.00882-21

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