The CRISPR/Cas9 system inactivates latent HIV-1 proviral DNA.
Retrovirology
; 12: 22, 2015 Feb 27.
Article
em En
| MEDLINE
| ID: mdl-25808449
ABSTRACT
BACKGROUND:
Highly active antiretroviral therapy (HAART) has transformed HIV-1 infection from a deadly disease to a manageable chronic illness, albeit does not provide a cure. The recently developed genome editing system called CRISPR/Cas9 offers a new tool to inactivate the integrated latent HIV-1 DNA and may serve as a new avenue toward cure.FINDINGS:
We tested 10 sites in HIV-1 DNA that can be targeted by CRISPR/Cas9. The engineered CRISPR/Cas9 system was introduced into the JLat10.6 cells that are latently infected by HIV-1. The sequencing results showed that each target site in HIV-1 DNA was efficiently mutated by CRISPR/Cas9 with the target site in the second exon of Rev (called T10) exhibiting the highest degree of mutation. As a result, HIV-1 gene expression and virus production were significantly diminished with T10 causing a 20-fold reduction.CONCLUSIONS:
The CRISPR/Cas9 complex efficiently mutates and deactivates HIV-1 proviral DNA in latently infected Jurkat cells. Our results also revealed a highly efficient Cas9 target site within the second exon of Rev that represents a promising target to be further explored in the CRISPR/Cas9-based cure strategy.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
DNA Viral
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HIV-1
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Provírus
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Latência Viral
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Sistemas CRISPR-Cas
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article