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CRISPR/Cas9 与人工智能的整合以改进癌症治疗

英文原题:Integration of CRISPR/Cas9 with artificial intelligence for improved cancer therapeutics.

查看英文原题

Integration of CRISPR/Cas9 with artificial intelligence for improved cancer therapeutics.

PubMed 2022/11/18(内容时间) J Transl Med Q1 · IF 9.7(JCR 2025)

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中文摘要

基因编辑在治疗由明确分子改变所致的疾病方面具有巨大潜力。成簇规律间隔短回文重复序列(CRISPR)/CRISPR相关蛋白9(Cas9)基因编辑工具的问世,显著提高了基因编辑的精确性和效率。与现有基因编辑方法相比,CRISPR/Cas9具有多项优势,例如几乎能够靶向任何基因组序列,从而可快速开发和应用新的CRISPR介导基因敲除/敲入方法。CRISPR/Cas9已广泛用于构建癌症模型、验证可成药的关键基因、研究耐药机制、探索非编码基因区域以及开发生物标志物。CRISPR基因编辑还可构建更有效、持久、成本更低且更易获得的嵌合抗原受体(CAR)T细胞。

不过,仍需进一步研究以明确CRISPR/Cas9系统的优缺点、建立最佳实践,并评估其社会和伦理影响。本文综述CRISPR/Cas9近期进展,重点介绍其在癌症研究和免疫治疗中的应用,以及基于CRISPR/Cas9的筛选在开发癌症精准医学和靶向治疗工程模型方面的潜力,并指出现有挑战与未来方向。

最后,本文讨论人工智能在优化CRISPR系统靶向和脱靶效应方面的作用;这对于其更广泛应用于癌症治疗至关重要。

展开英文摘要原文

Gene editing has great potential in treating diseases caused by well-characterized molecular alterations. The introduction of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-based gene-editing tools has substantially improved the precision and efficiency of gene editing. The CRISPR/Cas9 system offers several advantages over the existing gene-editing approaches, such as its ability to target practically any genomic sequence, enabling the rapid development and deployment of novel CRISPR-mediated knock-out/knock-in methods.

CRISPR/Cas9 has been widely used to develop cancer models, validate essential genes as druggable targets, study drug-resistance mechanisms, explore gene non-coding areas, and develop biomarkers. CRISPR gene editing can create more-effective chimeric antigen receptor (CAR)-T cells that are durable, cost-effective, and more readily available.

However, further research is needed to define the CRISPR/Cas9 system's pros and cons, establish best practices, and determine social and ethical implications. This review summarizes recent CRISPR/Cas9 developments, particularly in cancer research and immunotherapy, and the potential of CRISPR/Cas9-based screening in developing cancer precision medicine and engineering models for targeted cancer therapy, highlighting the existing challenges and future directions.

Lastly, we highlight the role of artificial intelligence in refining the CRISPR system's on-target and off-target effects, a critical factor for the broader application in cancer therapeutics.

论文信息

作者
Bhat AA、Nisar S、Mukherjee S、Saha N、Yarravarapu N、Lone SN、Masoodi T、Chauhan R
第一作者单位
Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha, Qatar.
通讯作者单位
Laboratory Animal Research Center, Qatar University, Doha, Qatar. Mohammad.Haris@pennmedicine.upenn.edu.
文献类型
综述 · 非美国政府资助研究
期刊
Journal of translational medicine2022 Nov 18
原文标识
PubMed 36401282 · DOI 10.1186/s12967-022-03765-1