CRISPR/Cas9-Mediated Gene Correction in Newborn Rabbits with Hereditary Tyrosinemia Type I.

Molecular Therapy : the Journal of the American Society of Gene Therapy
Nan LiKepin Wang

Abstract

Patients with hereditary tyrosinemia type I (HT1) present acute and irreversible liver and kidney damage during infancy. CRISPR-Cas9-mediated gene correction during infancy may provide a promising approach to treat patients with HT1. However, all previous studies were performed on adult HT1 rodent models, which cannot authentically recapitulate some symptoms of human patients. The efficacy and safety should be verified in large animals to translate precise gene therapy to clinical practice. Here, we delivered CRISPR-Cas9 and donor templates via adeno-associated virus to newborn HT1 rabbits. The lethal phenotypes could be rescued, and notably, these HT1 rabbits reached adulthood normally without 2-(2-nitro-4-trifluoromethylbenzyol)-1,3 cyclohexanedione administration and even gave birth to offspring. Adeno-associated virus (AAV)-treated HT1 rabbits displayed normal liver and kidney structures and functions. Homology-directed repair-mediated precise gene corrections and non-homologous end joining-mediated out-of-frame to in-frame corrections in the livers were observed with efficiencies of 0.90%-3.71% and 2.39%-6.35%, respectively, which appeared to be sufficient to recover liver function and decrease liver and kidney damage. Thi...Continue Reading

References

Sep 3, 2003·Pharmacology & Therapeutics·Jianglin Fan, Teruo Watanabe
Sep 30, 2004·Gene Therapy·S N WaddingtonC Coutelle
Feb 24, 2006·Pediatric Research·Saskia M M JacobsInge E T van den Berg
Feb 18, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Nicole K PaulkMarkus Grompe
Jun 16, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Raymond D HickeyMarkus Grompe
Oct 29, 2011·Methods in Molecular Biology·Mark S Sands
May 23, 2012·Journal of Hepatology·René AdamUNKNOWN European Liver and Intestine Transplant Association (ELITA)
Jan 5, 2013·Science·Le CongFeng Zhang
Jan 5, 2013·Science·Prashant MaliGeorge M Church
Apr 1, 2014·Nature Biotechnology·Hao YinDaniel G Anderson
Aug 2, 2014·Orphanet Journal of Rare Diseases·Sebene MayorandanAnibh Das
Nov 20, 2015·Nucleic Acids Research·Melissa J LandrumDonna R Maglott
Jul 29, 2016·Science Translational Medicine·Raymond D HickeyScott L Nyberg
Jan 6, 2017·The Journal of Biological Chemistry·Li LiLiangxue Lai
Mar 7, 2018·The Journal of Biological Chemistry·Yanjiao ShaoDali Li
Feb 3, 2019·Nature Reviews. Drug Discovery·Dan WangGuangping Gao
Feb 20, 2019·Nature Medicine·Olaya Santiago-FernándezCarlos López-Otín
Feb 20, 2019·Nature Medicine·Ergin BeyretJuan Carlos Izpisua Belmonte
Nov 20, 2019·Nature Biomedical Engineering·Chun-Qing SongWen Xue

❮ Previous
Next ❯

Citations

May 18, 2021·Molecular Therapy. Methods & Clinical Development·Peng GuWeiwang Gu
Mar 25, 2021·Gene Expression·Vivek ChowdharyKalpana Ghoshal
Aug 29, 2021·Life Sciences·Ritika LuthraKriti Bhandari

❮ Previous
Next ❯

Related Concepts

Related Feeds

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.

CRISPR for Genome Editing

Genome editing technologies enable the editing of genes to create or correct mutations. Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). Here is the latest research on the use of CRISPR-Cas system in gene editing.

Related Papers

Advances in Experimental Medicine and Biology
Grant A Mitchell, Hao Yang
Annals of Hepatology
Cynthia Fernández-LainezMarcela Vela-Amieva
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences
Yue Tang, Yuanyuan Kong
© 2021 Meta ULC. All rights reserved