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Efficient Inhibition of HIV Using CRISPR/Cas13d Nuclease System.
- Source :
-
Viruses [Viruses] 2021 Sep 16; Vol. 13 (9). Date of Electronic Publication: 2021 Sep 16. - Publication Year :
- 2021
-
Abstract
- Recently discovered Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas13 proteins are programmable RNA-guided ribonucleases that target single-stranded RNA (ssRNA). CRISPR/Cas13-mediated RNA targeting has emerged as a powerful tool for detecting and eliminating RNA viruses. Here, we demonstrate the effectiveness of CRISPR/Cas13d to inhibit HIV-1 replication. We designed guide RNAs (gRNAs) targeting highly conserved regions of HIV-1. RfxCas13d (CasRx) in combination with HIV-specific gRNAs efficiently inhibited HIV-1 replication in cell line models. Furthermore, simultaneous targeting of four distinct, non-overlapping sites in the HIV-1 transcript resulted in robust inhibition of HIV-1 replication. We also show the effective HIV-1 inhibition in primary CD4 <superscript>+</superscript> T-cells and suppression of HIV-1 reactivated from latently infected cells using the CRISPR/Cas13d system. Our study demonstrates the utility of the CRISPR/Cas13d nuclease system to target acute and latent HIV infection and provides an alternative treatment modality against HIV.
- Subjects :
- CD4-Positive T-Lymphocytes virology
Cells, Cultured
HEK293 Cells
Humans
Proviruses physiology
RNA, Guide, CRISPR-Cas Systems genetics
RNA, Guide, CRISPR-Cas Systems metabolism
RNA, Viral metabolism
Virus Replication
CRISPR-Associated Proteins metabolism
CRISPR-Cas Systems
Endodeoxyribonucleases metabolism
HIV-1 genetics
HIV-1 physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1999-4915
- Volume :
- 13
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Viruses
- Publication Type :
- Academic Journal
- Accession number :
- 34578431
- Full Text :
- https://doi.org/10.3390/v13091850