Journal
MOLECULAR THERAPY-NUCLEIC ACIDS
Volume 12, Issue -, Pages 267-274Publisher
CELL PRESS
DOI: 10.1016/j.omtn.2018.05.012
Keywords
-
Categories
Funding
- National Natural Science Foundation of China [81571991]
- Nankai University starting fund [ZB15006101]
Ask authors/readers for more resources
C-C chemokine receptor type 5 (CCR5) is the main co-receptor for HIV entry into the target CD4+ cells, and homozygous CCR5 Delta 32/Delta 32 cells are resistant to CCR5-tropic HIV infection. However, the CCR5 Delta 32/Delta 32 homozygous donors in populations are rare. Here we developed a simple approach to induce CCR5 Delta 32/Delta 32 homozygotes through CRISPR-Cas9 genome-editing technology. Designing a pair of single-guide RNA targeting the flank region of the CCR5 Delta 32 mutation locus, we applied the CRISPR-Cas9 and lentiviral packaging system to successfully convert wild-type CCR5 into CCR5 Delta 32/Delta 32 homozygotes in the human Jurkat CD4+ cell line and primary CD4+ cells, exactly the same as the naturally occurring CCR5 Delta 32/Delta 32 mutation. The successful rate is up to 20% in Jurkat cells but less in primary CD4+ cells. The modified CCR5 Delta 32/Delta 32 CD4+ cells are resistant to CCR5-tropic HIV infection. Whole-genome sequencing revealed no apparent off-target sites. This approach has the promise to promote HIV/AIDS therapy from the only cured unique Berlin patient to a routine autologous cell-based therapy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available