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Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo
- Source :
- Yin, H., C. Song, J. R. Dorkin, L. J. Zhu, Y. Li, Q. Wu, A. Park, et al. 2017. “Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo.” Nature biotechnology 34 (3): 328-333. doi:10.1038/nbt.3471. http://dx.doi.org/10.1038/nbt.3471.
- Publication Year :
- 2017
-
Abstract
- The combination of Cas9, guide RNA and repair template DNA can induce precise gene editing and the correction of genetic diseases in adult mammals. However, clinical implementation of this technology requires safe and effective delivery of all of these components into the nuclei of the target tissue. Here, we combine lipid nanoparticle–mediated delivery of Cas9 mRNA with adeno-associated viruses encoding a sgRNA and a repair template to induce repair of a disease gene in adult animals. We applied our delivery strategy to a mouse model of human hereditary tyrosinemia and show that the treatment generated fumarylacetoacetate hydrolase (Fah)-positive hepatocytes by correcting the causative Fah-splicing mutation. Treatment rescued disease symptoms such as weight loss and liver damage. The efficiency of correction was >6% of hepatocytes after a single application, suggesting potential utility of Cas9-based therapeutic genome editing for a range of diseases.
Details
- Language :
- English
- Database :
- Digital Access to Scholarship at Harvard (DASH)
- Journal :
- Yin, H., C. Song, J. R. Dorkin, L. J. Zhu, Y. Li, Q. Wu, A. Park, et al. 2017. “Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo.” Nature biotechnology 34 (3): 328-333. doi:10.1038/nbt.3471. http://dx.doi.org/10.1038/nbt.3471.
- Publication Type :
- Academic Journal
- Accession number :
- edshld.1.33029707
- Document Type :
- Journal Article
- Full Text :
- https://doi.org/10.1038/nbt.3471