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CRISPR/Cas9作为三阴性乳腺癌的治疗工具:从实验台到临床应用

CRISPR/Cas9 as a therapeutic tool for triple negative breast cancer: from bench to clinics.

作者信息

Tiwari Prashant Kumar, Ko Tin-Hsien, Dubey Rajni, Chouhan Mandeep, Tsai Lung-Wen, Singh Himanshu Narayan, Chaubey Kundan Kumar, Dayal Deen, Chiang Chih-Wei, Kumar Sanjay

机构信息

Biological and Bio-Computational Lab, Department of Life Sciences, Sharda School of Basic Science and Research, Sharda University, Greater Noida, Uttar Pradesh, India.

Department of Orthopedics, Taipei Medical University Hospital, Taipei City, Taiwan.

出版信息

Front Mol Biosci. 2023 Jul 4;10:1214489. doi: 10.3389/fmolb.2023.1214489. eCollection 2023.

DOI:10.3389/fmolb.2023.1214489
PMID:37469704
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10352522/
Abstract

Clustered regularly interspaced short palindromic repeats (CRISPR) is a third-generation genome editing method that has revolutionized the world with its high throughput results. It has been used in the treatment of various biological diseases and infections. Various bacteria and other prokaryotes such as archaea also have CRISPR/Cas9 systems to guard themselves against bacteriophage. Reportedly, CRISPR/Cas9-based strategy may inhibit the growth and development of triple-negative breast cancer (TNBC) via targeting the potentially altered resistance genes, transcription, and epigenetic regulation. These therapeutic activities could help with the complex issues such as drug resistance which is observed even in TNBC. Currently, various methods have been utilized for the delivery of CRISPR/Cas9 into the targeted cell such as physical (microinjection, electroporation, and hydrodynamic mode), viral (adeno-associated virus and lentivirus), and non-viral (liposomes and lipid nano-particles). Although different models have been developed to investigate the molecular causes of TNBC, but the lack of sensitive and targeted delivery methods for genome editing tools limits their clinical application. Therefore, based on the available evidences, this review comprehensively highlighted the advancement, challenges limitations, and prospects of CRISPR/Cas9 for the treatment of TNBC. We also underscored how integrating artificial intelligence and machine learning could improve CRISPR/Cas9 strategies in TNBC therapy.

摘要

成簇规律间隔短回文重复序列(CRISPR)是一种第三代基因组编辑方法,其高通量的结果给世界带来了变革。它已被用于治疗各种生物疾病和感染。各种细菌以及古细菌等其他原核生物也拥有CRISPR/Cas9系统来保护自身免受噬菌体侵害。据报道,基于CRISPR/Cas9的策略可能通过靶向潜在改变的抗性基因、转录和表观遗传调控来抑制三阴性乳腺癌(TNBC)的生长和发展。这些治疗活性有助于解决诸如TNBC中甚至也会出现的耐药性等复杂问题。目前,已经采用了多种方法将CRISPR/Cas9递送至靶细胞,如物理方法(显微注射、电穿孔和流体动力学模式)、病毒方法(腺相关病毒和慢病毒)以及非病毒方法(脂质体和脂质纳米颗粒)。尽管已经开发了不同模型来研究TNBC的分子病因,但基因组编辑工具缺乏灵敏且有针对性的递送方法限制了它们的临床应用。因此,基于现有证据,本综述全面强调了CRISPR/Cas9治疗TNBC的进展、挑战、局限性及前景。我们还强调了整合人工智能和机器学习如何能够改进TNBC治疗中的CRISPR/Cas9策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a489/10352522/9a80dbe960f0/fmolb-10-1214489-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a489/10352522/b4cfc148c208/fmolb-10-1214489-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a489/10352522/c78eb553d416/fmolb-10-1214489-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a489/10352522/9a80dbe960f0/fmolb-10-1214489-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a489/10352522/b4cfc148c208/fmolb-10-1214489-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a489/10352522/c78eb553d416/fmolb-10-1214489-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a489/10352522/9a80dbe960f0/fmolb-10-1214489-g003.jpg

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本文引用的文献

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Funct Integr Genomics. 2023 May 26;23(2):182. doi: 10.1007/s10142-023-01117-w.
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Synthetic Epigenetic Reprogramming of Mesenchymal to Epithelial States Using the CRISPR/dCas9 Platform in Triple Negative Breast Cancer.利用 CRISPR/dCas9 平台在三阴性乳腺癌中对间充质到上皮状态进行合成表观遗传重编程。
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FRA-1 as a Regulator of EMT and Metastasis in Breast Cancer.
三阴性乳腺癌中的分子异质性与MYC失调:基因组学进展及治疗意义
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Unlocking the epigenetic code: new insights into triple-negative breast cancer.解开表观遗传密码:三阴性乳腺癌的新见解
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Advancing Phage Therapy: A Comprehensive Review of the Safety, Efficacy, and Future Prospects for the Targeted Treatment of Bacterial Infections.推进噬菌体疗法:针对细菌感染靶向治疗的安全性、有效性及未来前景的全面综述
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