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CRISPR/Cas9疗法:治疗癌症及其他遗传疾病的方法。

CRISPR/Cas9 therapeutics: a cure for cancer and other genetic diseases.

作者信息

Khan Faheem Ahmed, Pandupuspitasari Nuruliarizki Shinta, Chun-Jie Huang, Ao Zhou, Jamal Muhammad, Zohaib Ali, Khan Farhan Ahmed, Hakim Muthia Raihana, ShuJun Zhang

机构信息

Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Education Ministry of China, Huazhong Agricultural University, Wuhan, People's Republic of China.

State Key Laboratory of Agriculture Microbiology, Huazhong Agricultural University, Wuhan, People's Republic of China.

出版信息

Oncotarget. 2016 Aug 9;7(32):52541-52552. doi: 10.18632/oncotarget.9646.

Abstract

Cancer is caused by a series of alterations in genome and epigenome mostly resulting in activation of oncogenes or inactivation of cancer suppressor genes. Genetic engineering has become pivotal in the treatment of cancer and other genetic diseases, especially the formerly-niche use of clustered regularly interspaced short palindromic repeats (CRISPR) associated with Cas9. In defining its superior use, we have followed the recent advances that have been made in producing CRISPR/Cas9 as a therapy of choice. We also provide important genetic mutations where CRISPRs can be repurposed to create adaptive immunity to fight carcinomas and edit genetic mutations causing it. Meanwhile, challenges to CRISPR technology are also discussed with emphasis on ability of pathogens to evolve against CRISPRs. We follow the recent developments on the function of CRISPRs with different carriers which can efficiently deliver it to target cells; furthermore, analogous technologies are also discussed along CRISPRs, including zinc-finger nuclease (ZFN) and transcription activator-like effector nucleases (TALENs). Moreover, progress in clinical applications of CRISPR therapeutics is reviewed; in effect, patients can have lower morbidity and/or mortality from the therapeutic method with least possible side-effects.

摘要

癌症是由基因组和表观基因组的一系列改变引起的,这些改变大多导致癌基因激活或抑癌基因失活。基因工程在癌症和其他遗传疾病的治疗中已变得至关重要,尤其是与Cas9相关的成簇规律间隔短回文重复序列(CRISPR)这种以前小众的应用。在确定其卓越用途时,我们追踪了在将CRISPR/Cas9作为首选治疗方法方面取得的最新进展。我们还提供了重要的基因突变,在这些突变中,CRISPR可被重新利用以产生适应性免疫来对抗癌症并编辑导致癌症的基因突变。同时,也讨论了CRISPR技术面临的挑战,重点是病原体针对CRISPR进化的能力。我们追踪了关于不同载体的CRISPR功能的最新进展,这些载体能够有效地将其递送至靶细胞;此外,还沿着CRISPR讨论了类似技术,包括锌指核酸酶(ZFN)和转录激活样效应核酸酶(TALENs)。此外,还综述了CRISPR疗法临床应用的进展;实际上,患者采用这种治疗方法可降低发病率和/或死亡率,且副作用最小。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e16/5239572/9b69f2545969/oncotarget-07-52541-g001.jpg

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