A temperature-sensitive and less immunogenic Sendai virus for efficient gene editing
Gene editing has the potential to be a powerful tool for the treatment of human diseases including HIV, β-thalassemias, and sickle cell disease. Recent advances have begun to overcome one of the major limiting factors of this technology, namely delivery of the CRISPR-Cas9 gene editing machinery, by utilizing viral vectors. However, gene editing therapies have yet to be implemented due to inherent risks associated with the DNA viral vectors typically used for delivery. As an alternative strategy, we have developed an RNA-based Sendai virus CRISPR-Cas9 delivery vector that does not integrate into the genome, is temperature sensitive, and does not induce a significant host interferon response. This recombinant SeV successfully delivered CRISPR-Cas9 in primary human CD14+ monocytes <i>ex vivo</i> resulting in a high level of CCR5 editing and inhibition of HIV infection.
Authors
- Ruth Watkinson (ORCID: https://orcid.org/0000-0001-6218-6785)
- Olivier Pernet (ORCID: https://orcid.org/0000-0003-0633-7360)
- Wannisa Khamaikawin (ORCID: https://orcid.org/0000-0001-6766-6841)
- Patrick Hong (ORCID: https://orcid.org/0000-0002-3701-1497)
- Christian S. Stevens (ORCID: https://orcid.org/0000-0003-2472-6984)
- Patricia A. Thibault (ORCID: https://orcid.org/0000-0002-7313-0848)
- Benhur Lee (ORCID: https://orcid.org/0000-0003-0760-1709)
- Arnold Park (ORCID: https://orcid.org/0000-0001-8916-2230)
- Jillian C. Carmichael (ORCID: https://orcid.org/0000-0001-5270-5916)
- Dong Sung An (ORCID: https://orcid.org/0000-0002-7020-9470)
- Kory Hamane
- Aditya Gowlikar
- Rebecca A. Reis (ORCID: https://orcid.org/0000-0002-6118-1509)
- Jason Jang
- Shreyas Kowdle
Institutions
- University of California, Los Angeles (US)
- Black AIDS Institute (US)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Journal of Virology
- Published
- 2024-11-04
- DOI
- https://doi.org/10.1128/jvi.00832-24
- Citations
- 2
- Primary Topic
- CRISPR and Genetic Engineering
- Type
- article
- Field-Weighted Citation Impact
- 0.47
Funders
- European Molecular Biology Organization
- National Institutes of Health
- Canadian Institutes of Health Research
- National Institute of Allergy and Infectious Diseases