Therapeutic editing of hepatocyte genome in vivo

JOURNAL OF HEPATOLOGY

卷:67

Review

de Galarreta, Marina Ruiz^1,2  Lujambio, Amaia^1,2,3 

[1] Icahn Sch Med Mt Sinai, Oncol Sci Dept, New York, NY 10029 USA

[2] Icahn Sch Med Mt Sinai, Dept Med, Tisch Canc Inst, Liver Canc Program,Div Liver Dis, 1470 Madison Ave Hess 6-111, New York, NY 10029 USA

[3] Icahn Sch Med Mt Sinai, Grad Sch Biomed Sci, New York, NY 10029 USA

关键词: Gene editing;    Meganucleases;    ZFNs;    TALENs;    CRISPR-Cas nucleases;    Liver hereditary diseases;   

DOI  :  10.1016/j.jhep.2017.05.012

来源: Elsevier

【 摘 要 】

The recent development of gene editing platforms enables making precise changes in the genome of eukaryotic cells. Programmable nucleases, such as meganucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)-associated nucleases have revolutionized the way research is conducted as they facilitate the rapid production of mutant or knockout cellular and animal models. These same genetic tools can potentially be applied to cure or alleviate a variety of diseases, including genetic diseases that lack an efficient therapy. Thus, gene editing platforms could be used for correcting mutations that cause a disease, restoration of the expression of genes that are missing, or be used for the removal of deleterious genes or viral genomes. In the context of liver diseases, genome editing could be developed to treat not only hereditary monogenic liver diseases but also hepatitis B infection and diseases that have both genetic and non-genetic components. While the prospect of translating these therapeutic strategies to a clinical setting is highly appealing, there are numerous challenges that need to be addressed first. Safety, efficiency, specificity, and delivery are some of the obstacles that will need to be addressed before each specific gene treatment is safely used in patients. Here, we discuss the most used gene editing platforms, their mechanisms of action, their potential for liver disease treatment, the most pressing challenges, and future prospects. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

【 授权许可】

Free