CRISPR-Cas9 gene editing: Delivery aspects and therapeutic potential

JOURNAL OF CONTROLLED RELEASE

卷:244

Article; Proceedings Paper

Blenke, Erik Oude¹  Evers, Martijn J. W.¹  Mastrobattista, Enrico¹  van der Oost, John² 

[1] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Dept Pharmaceut, Univ Weg 99, NL-3584 CG Utrecht, Netherlands

[2] Wageningen Univ, Microbiol Lab, Dreijenpl 10, NL-6703 HB Wageningen, Netherlands

关键词: CRISPR-Cas;    CRISPR-Cas9;    Gene editing;    Genome editing;    Delivery systems;    Therapeutic applications;    In vivo;    Ex vivo;   

DOI  :  10.1016/j.jconrel.2016.08.002

来源: Elsevier

【 摘 要 】

The CRISPR-Cas9 gene editing system has taken the biomedical science field by storm, initiating rumors about future Nobel Prizes and heating up a fierce patent war, but also making significant scientific impact. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), together with CRISPR-associated proteins (Cas) are a part of the prokaryotic adaptive immune system and have successfully been repurposed for genome editing in mammalian cells. The CRISPR-Cas9 system has been used to correct genetic mutations and for replacing entire genes, opening up a world of possibilities for the treatment of genetic diseases. In addition, recently some new CRISPR-Cas systems have been discovered with interesting mechanistic variations. Despite these promising developments, many challenges have to be overcome before the system can be applied therapeutically in human patients and enabling delivery technology is one of the key challenges. Furthermore, the relatively high off-target effect of the system in its current form prevents it from being safely applied directly in the human body. In this review, the transformation of the CRISPR-Cas gene editing systems into a therapeutic modality will be discussed and the currently most realistic in vivo applications will be highlighted. (C) 2016 Elsevier B.V. All rights reserved.

【 授权许可】

Free