Thumbnail Image
Item

Elimination of HIV-1 Genomes from Human T-lymphoid Cells by CRISPR/Cas9 Gene Editing

; 
Chen, Yilan
; 
Fischer, Tracy
; 
Tedaldi, Ellen
; ; 
Zhang, Yonggang
; 
Karn, Jonathan
; 
Hu, Wenhui
; 
Khalili, Kamel
Citations
Altmetric:
Genre
Journal article
Date
2016-03-03
Advisor
Committee member
Group
Center for Neurovirology (Temple University)
Comprehensive NeuroAIDS Center (CNAC) (Temple University)
Department
Neuroscience
Medicine
Subject
HIV infections
 Microbiology
Permanent link to this record
http://hdl.handle.net/20.500.12613/380
Collections
Faculty/Researcher Works
Show all metadata
Files
Thumbnail Image
Kaminski-JournalArticle-2016.pdf
Adobe PDF, 5.63 MB
Thumbnail Image
Supplementary Materials
Adobe PDF, 2.07 MB
Research Projects
Organizational Units
Journal Issue
DOI
https://doi.org/10.1038/srep22555
Abstract
We employed an RNA-guided CRISPR/Cas9 DNA editing system to precisely remove the entire HIV-1 genome spanning between 5′ and 3′ LTRs of integrated HIV-1 proviral DNA copies from latently infected human CD4+ T-cells. Comprehensive assessment of whole-genome sequencing of HIV-1 eradicated cells ruled out any off-target effects by our CRISPR/Cas9 technology that might compromise the integrity of the host genome and further showed no effect on several cell health indices including viability, cell cycle and apoptosis. Persistent co-expression of Cas9 and the specific targeting guide RNAs in HIV-1-eradicated T-cells protected them against new infection by HIV-1. Lentivirus-delivered CRISPR/Cas9 significantly diminished HIV-1 replication in infected primary CD4+ T-cell cultures and drastically reduced viral load in ex vivo culture of CD4+ T-cells obtained from HIV-1 infected patients. Thus, gene editing using CRISPR/Cas9 may provide a new therapeutic path for eliminating HIV-1 DNA from CD4+ T-cells and potentially serve as a novel and effective platform toward curing AIDS.
Description
Citation
Kaminski, R., Chen, Y., Fischer, T. et al. Elimination of HIV-1 Genomes from Human T-lymphoid Cells by CRISPR/Cas9 Gene Editing. Sci Rep 6, 22555 (2016). https://doi.org/10.1038/srep22555
Citation to related work
Nature Research
Has part
Scientific Reports, Vol. 6, Article 22555
ADA compliance
For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
Embedded videos