研究动态
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基于CRISPR/Cas9的癌症治疗应用:非病毒载体递送的挑战与解决方案。

CRISPR/Cas9-based application for cancer therapy: Challenges and solutions for non-viral delivery.

发表日期:2023 Aug 15
作者: Ying-Qi Lin, Ke-Ke Feng, Jie-Ying Lu, Jing-Qing Le, Wu-Ling Li, Bing-Chen Zhang, Cheng-Lei Li, Xun-Huan Song, Ling-Wu Tong, Jing-Wei Shao
来源: GENES & DEVELOPMENT

摘要:

CRISPR/Cas9基因组编辑技术是一种有前景的治疗技术,因其高敏感性和高效性使得精确快速的基因编辑成为可能。CRISPR/Cas9系统已被证明能有效地干扰和修改基因,显示出在癌症治疗中具有巨大潜力。当前研究证明病毒载体能够有效地传递CRISPR/Cas9系统,但由病毒传播引起的免疫原性和致癌性仍然引发严重后果。因此,CRISPR/Cas9在癌症治疗中的最大挑战在于如何安全有效地将其传递到目标肿瘤部位。具有特异性靶向、高负载能力和低免疫毒性的非病毒传递系统比受限于无法控制的副作用的病毒载体更适合。其医学进展和应用受到了广泛关注。本文从研究开始阐述了CRISPR/Cas9系统编辑基因的分子机制和不同的构建策略。随后,介绍了几种常见的CRISPR/Cas9非病毒传递系统在癌症治疗中的应用。最后,基于现有研究和文献提出了限制非病毒载体传递效率的主要因素,并总结和讨论了解决这些限制的主要方法,旨在进一步优化和创新适用于癌症治疗的CRISPR/Cas9非病毒传递系统。版权所有 © 2023. Elsevier B.V. 发表。
CRISPR/Cas9 genome editing is a promising therapeutic technique, which makes precise and rapid gene editing technology possible on account of its high sensitivity and efficiency. CRISPR/Cas9 system has been proved to able to effectively disrupt and modify genes, which shows great potential for cancer treatment. Current researches proves that virus vectors are capable of effectively delivering the CRISPR/Cas9 system, but immunogenicity and carcinogenicity caused by virus transmission still trigger serious consequences. Therefore, the greatest challenge of CRISPR/Cas9 for cancer therapy lies on how to deliver it to the target tumor site safely and effectively. Non-viral delivery systems with specific targeting, high loading capacity, and low immune toxicity are more suitable than viral vectors, which limited by uncontrollable side effects. Their medical advances and applications have been widely concerned. Herein, we present the molecule mechanism and different construction strategies of CRISPR/Cas9 system for editing genes at the beginning of this research. Subsequently, several common CRISPR/Cas9 non-viral deliveries for cancer treatment are introduced. Lastly, based on the main factors limiting the delivery efficiency of non-viral vectors proposed in the existing researches and literature, we summarize and discuss the main methods to solve these limitations in the existing tumor treatment system, aiming to introduce further optimization and innovation of the CRISPR/Cas9 non-viral delivery system suitable for cancer treatment.Copyright © 2023. Published by Elsevier B.V.