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Targeted Chromatinization and Repression of HIV-1 Provirus Transcription with Repurposed CRISPR/Cas9.
- Source :
-
Viruses (1999-4915) . Oct2020, Vol. 12 Issue 10, p1154. 1p. - Publication Year :
- 2020
-
Abstract
- The major barrier to HIV-1 cure is the persistence of latent provirus, which is not eradicated by antiretroviral therapy. The "shock and kill" approach entails stimulating viral production with latency-reversing agents followed by the killing of cells actively producing the virus by immune clearance. However, this approach does not induce all intact proviruses, leaving a residual reservoir. CRISPR/Cas9 has been utilized to excise integrated Human Immunodeficiency Virus (HIV) DNA from infected cells in an RNA-guided, sequence-specific manner. Here, we seek to epigenetically silence the proviral DNA by introducing nuclease-deficient disabled Cas9 (dCas9) coupled with a transcriptional repressor domain derived from Kruppel-associated box (KRAB). We show that specific guide RNAs (gRNAs) and dCas9-KRAB repress HIV-1 transcription and reactivation of latent HIV-1 provirus. This repression is correlated with chromatin changes, including decreased H3 histone acetylation and increased histone H3 lysine 9 trimethylation, histone marks that are associated with transcriptional repression. dCas9-KRAB-mediated inhibition of HIV-1 transcription suggests that CRISPR can be engineered as a tool for block-and-lock strategies. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 19994915
- Volume :
- 12
- Issue :
- 10
- Database :
- Academic Search Index
- Journal :
- Viruses (1999-4915)
- Publication Type :
- Academic Journal
- Accession number :
- 146654499
- Full Text :
- https://doi.org/10.3390/v12101154