Title |
Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo
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Published in |
Nature Biotechnology, February 2016
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DOI | 10.1038/nbt.3471 |
Pubmed ID | |
Authors |
Hao Yin, Chun-Qing Song, Joseph R Dorkin, Lihua J Zhu, Yingxiang Li, Qiongqiong Wu, Angela Park, Junghoon Yang, Sneha Suresh, Aizhan Bizhanova, Ankit Gupta, Mehmet F Bolukbasi, Stephen Walsh, Roman L Bogorad, Guangping Gao, Zhiping Weng, Yizhou Dong, Victor Koteliansky, Scot A Wolfe, Robert Langer, Wen Xue, Daniel G Anderson |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 17 | 26% |
United Kingdom | 4 | 6% |
France | 4 | 6% |
Japan | 3 | 5% |
Belgium | 2 | 3% |
Germany | 2 | 3% |
Austria | 1 | 2% |
Australia | 1 | 2% |
Denmark | 1 | 2% |
Other | 3 | 5% |
Unknown | 28 | 42% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 38 | 58% |
Scientists | 26 | 39% |
Science communicators (journalists, bloggers, editors) | 2 | 3% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 8 | <1% |
Germany | 3 | <1% |
Finland | 2 | <1% |
Turkey | 2 | <1% |
Spain | 2 | <1% |
Netherlands | 1 | <1% |
China | 1 | <1% |
Canada | 1 | <1% |
Belgium | 1 | <1% |
Other | 1 | <1% |
Unknown | 1077 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 234 | 21% |
Researcher | 174 | 16% |
Student > Bachelor | 154 | 14% |
Student > Master | 122 | 11% |
Student > Doctoral Student | 55 | 5% |
Other | 145 | 13% |
Unknown | 215 | 20% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 328 | 30% |
Agricultural and Biological Sciences | 219 | 20% |
Engineering | 55 | 5% |
Medicine and Dentistry | 50 | 5% |
Chemistry | 42 | 4% |
Other | 152 | 14% |
Unknown | 253 | 23% |