Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo
By Hao Yin, Chun‐Qing Song, J. R. Dorkin, Lihua Julie Zhu, Yingxiang Li, Qiongqiong Wu, Angela I. Park, Jung H. Yang, Sneha Suresh, Aizhan Bizhanova and 12 more. Nature Biotechnology, 2016
823 citations recorded by the source corpus.
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.
Subfields: Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/1129d2a7b8019bb5cab4883aafd21f085b1062ba
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In Molecular Biology
Citations in the corpus
- Engineering the Delivery System for CRISPR-based Genome Editing (2018, methodology): “Some groups have used a hybrid method in which mRNA encoding for the Cas9 protein is co-delivered with a viral genome constitutively expressing the gRNA in order to avoid this timing issue altogether [23].”
- Delivering CRISPR: a review of the challenges and approaches (2018, methodology): “If delivering Cas9 mRNA and sgRNA, this method is functionally like microinjection in result (Yin et al., 2016).”