Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo

Nature Biotechnology
Hao YinDaniel 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.

References

Jan 7, 1998·Molecular and Cellular Biology·B ElliottM Jasin
Feb 24, 2001·Proceedings of the National Academy of Sciences of the United States of America·J L AponteD K Johnson
Oct 1, 2005·Molecular Biology of the Cell·Kamran AtabaiDean Sheppard
Aug 1, 2007·Nature Biotechnology·Hisaya AzumaMarkus Grompe
Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Kevin T LoveDaniel G Anderson
Jan 19, 2010·Nature Biotechnology·Sean C SempleMichael J Hope
Feb 18, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Nicole K PaulkMarkus Grompe
May 13, 2010·BMC Bioinformatics·Lihua J ZhuMichael R Green
Jan 11, 2011·Nature Biotechnology·Michael S D KormannCarsten Rudolph
Apr 7, 2011·Nature Reviews. Genetics·Mark A Kay
Apr 6, 2012·Journal of the American Chemical Society·Delai ChenDaniel G Anderson
Oct 16, 2012·Nature Cell Biology·Hui-Zi ChenGustavo Leone
Nov 8, 2012·Development·Sakthi SundararajanJaime A Rivera-Pérez
Jan 5, 2013·Science·Le CongFeng Zhang
Jan 5, 2013·Science·Prashant MaliGeorge M Church
Jun 25, 2013·Nature Biotechnology·Yanfang FuJeffry D Sander
Jul 23, 2013·Nature Biotechnology·Patrick D HsuFeng Zhang
Oct 1, 2013·Nature Methods·Prashant MaliGeorge M Church
Dec 10, 2013·Cell Stem Cell·Yuxuan WuJinsong Li
Mar 4, 2014·Nature Biotechnology·Jeffry D Sander, J Keith Joung
Apr 1, 2014·Nature Biotechnology·Hao YinDaniel G Anderson
Apr 23, 2014·Nature Biotechnology·Xuebing WuPhillip A Sharp
Jul 16, 2014·Nature Reviews. Genetics·Hao YinDaniel G Anderson
Aug 21, 2014·Nature·Gregory M FindlayJay Shendure
Oct 20, 2014·Nature Biotechnology·Lukasz SwiechFeng Zhang
Nov 29, 2014·Science·Jennifer A Doudna, Emmanuelle Charpentier
Dec 17, 2014·Nature Biotechnology·Shengdar Q TsaiJ Keith Joung
Feb 6, 2015·Nature Medicine·David Benjamin Turitz CoxFeng Zhang
Apr 2, 2015·Nature·F Ann RanFeng Zhang
May 20, 2015·Nature Biotechnology·Azita J MahinyMichael S D Kormann
Jun 30, 2015·Nature Biotechnology·Ayal HendelMatthew H Porteus
Oct 20, 2015·Nature Methods·Mehmet Fatih BolukbasiScot A Wolfe

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Citations

Apr 1, 2016·Gene Therapy·H-Y XueY Xu
Apr 30, 2016·International Journal of Molecular Sciences·Luyao WangGe Zhang
Jun 28, 2016·Nature Biotechnology·Benjamin P KleinstiverJ Keith Joung
Jul 8, 2016·Human Genetics·Channabasavaiah B GurumurthyXue Zhong Liu
Jul 21, 2016·Molecular Therapy. Nucleic Acids·Giridhar MurlidharanAravind Asokan
Aug 9, 2016·Briefings in Functional Genomics·Tomoko Kato, Shuji Takada
Aug 27, 2016·Briefings in Functional Genomics·Taeyoung Koo, Jin-Soo Kim
May 25, 2016·Annual Review of Genomics and Human Genetics·Xin XiongLei S Qi
Sep 7, 2016·Nature Methods·Wei Leong ChewGeorge M Church
Nov 5, 2016·Nature Reviews. Cardiology·Alanna Strong, Kiran Musunuru
Oct 1, 2016·Molecular Therapy : the Journal of the American Society of Gene Therapy·Yanhao ChenQiurong Ding
Jan 11, 2017·Hämostaseologie·Simone A HaasToni Cathomen
Jan 4, 2017·ACS Nano·Daniel JasinskiPeixuan Guo
Mar 1, 2017·Nature Biotechnology·Steven F Dowdy
Jan 12, 2017·Human Gene Therapy·Paul N Valdmanis, Mark A Kay
Apr 8, 2017·Nature Medicine·Tatjana I CornuToni Cathomen
Apr 11, 2017·Acta Pharmacologica Sinica·Gayong ShimYu-Kyoung Oh
Feb 10, 2017·Topics in Current Chemistry·Peng Zhang, Ernst Wagner
Apr 4, 2017·Molecular Therapy : the Journal of the American Society of Gene Therapy·Chaoran YinWenhui Hu
May 21, 2017·Science China. Life Sciences·Zhi-Yao HeYu-Quan Wei
May 4, 2017·Journal of Cellular Biochemistry·Han Zhang, Nami McCarty
May 31, 2017·ACS Synthetic Biology·Michael PinedaSamira Kiani
Mar 17, 2017·Scientific Reports·Kelsey E JarrettWilliam R Lagor
Apr 30, 2017·Chemical Science·Jessica A KretzmannK Swaminathan Iyer
Feb 28, 2017·BMC Medicine·Jessica L SchnellerCharles P Venditti
Jan 23, 2017·Molecular Therapy : the Journal of the American Society of Gene Therapy·Guo-Xiang RuanAbraham Scaria
Jul 8, 2017·ACS Applied Materials & Interfaces·Xinfu ZhangYizhou Dong
May 20, 2017·Nucleic Acids Research·Moe HirosawaHirohide Saito
Jun 18, 2017·The Journal of Gene Medicine·Puping LiangJunjiu Huang
Mar 7, 2018·The Journal of Biological Chemistry·Yanjiao ShaoDali Li
May 8, 2018·Advanced Materials·Owen S FentonRobert Langer
Apr 13, 2018·Human Gene Therapy·Lijuan YinFei Guo
Apr 29, 2018·Biotechnology Letters·Hasan Mollanoori, Shahram Teimourian
Oct 25, 2017·Biomaterials Science·Zhao MengWenxin Wang

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Methods Mentioned

BETA
gene knockout
dynamic light scattering
FACS
PCR
transfection
GUIDE-Seq
chemical modification
ELISArray
Illumina sequencing

Software Mentioned

ChIPpeakAnno
Prism
CRISPRseek
GraphPad
Seq
bwa
GUIDE
Bowtie

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