a Department of Chemistry , University of Massachusetts Amherst , Amherst , Massachusetts , USA.
b School of Chemical and Biotechnology , Sastra Deemed-to-be University,Tirumalaisamudram , Thanjavur , Tamil Nadu , India.
Expert Opin Drug Deliv. 2018 Sep;15(9):905-913. doi: 10.1080/17425247.2018.1517746. Epub 2018 Sep 12.
Therapeutic gene editing is becoming a viable biomedical tool with the emergence of the CRISPR/Cas9 system. CRISPR-based technologies have promise as a therapeutic platform for many human genetic diseases previously considered untreatable, providing a flexible approach to high-fidelity gene editing. For many diseases, such as sickle-cell disease and beta thalassemia, curative therapy may already be on the horizon, with CRISPR-based clinical trials slated for the next few years. Translation of CRISPR-based therapy to in vivo application however, is no small feat, and major hurdles remain for efficacious use of the CRISPR/Cas9 system in clinical contexts.
In this topical review, we highlight recent advances to in vivo delivery of the CRISPR/Cas9 system using various packaging formats, including viral, mRNA, plasmid, and protein-based approaches. We also discuss some of the barriers which have yet to be overcome for successful translation of this technology.
This review focuses on the challenges to efficacy for various delivery formats, with specific emphasis on overcoming these challenges through the development of carrier vehicles for transient approaches to CRISPR/Cas9 delivery in vivo.
随着 CRISPR/Cas9 系统的出现，治疗性基因编辑正在成为一种可行的生物医学工具。基于 CRISPR 的技术有望成为许多以前被认为无法治疗的人类遗传疾病的治疗平台，为高精度基因编辑提供了一种灵活的方法。对于许多疾病，如镰状细胞病和β地中海贫血症，治愈疗法可能已经在望，基于 CRISPR 的临床试验计划在未来几年进行。然而，将基于 CRISPR 的疗法转化为体内应用并非易事，在临床环境中有效使用 CRISPR/Cas9 系统仍然存在重大障碍。
在本次专题评论中，我们强调了使用各种包装格式（包括病毒、mRNA、质粒和蛋白质方法）将 CRISPR/Cas9 系统递送至体内的最新进展。我们还讨论了为成功转化这项技术仍需克服的一些障碍。
本评论重点介绍了各种递送格式的功效挑战，特别强调通过开发载体来克服这些挑战，以便对 CRISPR/Cas9 进行体内瞬时递送。
