[HTML][HTML] The CRISPR/Cas9 system inactivates latent HIV-1 proviral DNA
W Zhu, R Lei, Y Le Duff, J Li, F Guo, MA Wainberg… - Retrovirology, 2015 - Springer
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 …
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 …
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.
Springer