Genome editing systems in novel therapies.
Genome editing systems in novel therapies.
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DOI：
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发表时间：
2016
影响因子：
1.4
通讯作者：
Yoon-Young Jang;Liu-hong Cai;Zhaohui Ye
中科院分区：
文献类型：
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作者：
Yoon-Young Jang;Liu-hong Cai;Zhaohui Ye
基因组编辑是修改精确基因组位置的 DNA 序列的过程。在过去的三十年里，通过同源重组的基因组编辑已在小鼠中成功进行，用于生成遗传模型。然而，这一过程在人体细胞中的低效率阻碍了其临床应用，直到设计核酸内切酶技术的最新进展。 ZFN、TALEN 和 CRISPR 系统显着提高的基因组编辑效率不仅为生物医学研究提供了前所未有的机会，也为开发新疗法提供了前所未有的机会。基于这些基因组编辑工具的应用程序正在积极研究用于基因和细胞治疗目的，以破坏有害基因、纠正基因突变、更有效地传递功能性转基因，甚至修改表观遗传景观。过去两年，有限的临床试验取得了令人鼓舞的结果。虽然大多数应用仍处于原理验证或临床前开发阶段，但预计未来几年基于现代基因组编辑技术的新疗法将在临床上取得越来越多的成功。应该指出的是，在这些技术转化为更可靠的疗法之前，仍然存在关键问题。这些关键问题包括脱靶评估、建立合适的临床前模型以及改善目前基于同源性的精确基因替换的低效率。在这篇综述中，我们讨论了旨在转化基因组编辑技术的临床前和临床研究，以及对于更成功的转化而言重要的问题。
Genome editing is the process in which DNA sequences at precise genomic locations are modified. In the past three decades, genome editing by homologous recombination has been successfully performed in mouse for generating genetic models. The low efficiency of this process in human cells, however, had prevented its clinical application until the recent advancements in designer endonuclease technologies. The significantly improved genome editing efficiencies aided by ZFN, TALEN, and CRISPR systems provide unprecedented opportunities not only for biomedical research, but also for developing novel therapies. Applications based on these genome editing tools to disrupt deleterious genes, correct genetic mutations, deliver functional transgenes more effectively or even modify the epigenetic landscape are being actively investigated for gene and cell therapy purposes. Encouraging results have been obtained in limited clinical trials in the past two years. While most of the applications are still in proof-of-principle or preclinical development stages, it is anticipated that the coming years will see increasing clinical success in novel therapies based on the modern genome editing technologies. It should be noted that critical issues still remain before the technologies can be translated into more reliable therapies. These key issues include off-target evaluation, establishing appropriate preclinical models and improving the currently low efficiency of homology-based precise gene replacement. In this review we discuss the preclinical and clinical studies aiming at translating the genome editing technologies as well as the issues that are important for more successful translation.