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Exosome-mediated delivery of CRISPR-Cas9: A revolutionary approach to cancer gene editing.

作者信息

Balaraman Ashok Kumar, Babu M Arockia, Moglad Ehssan, Mandaliya Viralkumar, Rekha M M, Gupta Sofia, Prasad G V Siva, Kumari Mukesh, Chauhan Ashish Singh, Ali Haider, Goyal Kavita

机构信息

Research and Enterprise, University of Cyberjaya, Persiaran Bestari, Cyber 11, Cyberjaya, Selangor 63000, Malaysia.

Institute of Pharmaceutical Research, GLA UNIVERSITY, Mathura, UP 281406, India.

出版信息

Pathol Res Pract. 2025 Feb;266:155785. doi: 10.1016/j.prp.2024.155785. Epub 2024 Dec 19.


DOI:10.1016/j.prp.2024.155785
PMID:39708520
Abstract

Several molecular strategies based on targeted gene delivery systems have been developed in recent years; however, the CRISPR-Cas9 technology introduced a new era of targeted gene editing, precisely modifying oncogenes, tumor suppressor genes, and other regulatory genes involved in carcinogenesis. However, efficiently and safely delivering CRISPR-Cas9 to cancer cells across the cell membrane and the nucleus is still challenging. Using viral vectors and nanoparticles presents issues of immunogenicity, off-target effects, and low targeting affinity. Naturally, extracellular vesicles called exosomes have garnered the most attention as delivery vehicles in oncology-related CRISPR-Cas9 calls due to their biocompatibility, loading capacity, and inherent targeting features. The following review discusses the current progress in using exosomes to deliver CRISPR-Cas9 components, the approaches to load the CRISPR components into exosomes, and the modification of exosomes to increase stability and tumor-targeted delivery. We discuss the latest strategies in targeting recently accomplished in the exosome field, including modifying the surface of exosomes to enhance their internalization by cancer cells, as well as the measures taken to overcome the impacts of TME on delivery efficiency. Focusing on in vitro and in vivo experimentation, this review shows that exosome-mediated CRISPR-Cas9 can potentially treat cancer types, including pancreatic, lymphoma, and leukemia, for given gene targets. This paper compares exosome-mediated delivery and conventional vectors regarding safety, immune response, and targeting ability. Last but not least, we present the major drawbacks and potential development of the seemingly promising field of exosome engineering in gene editing, with references to CRISPR technologies and applications that may help make the target exosomes therapeutic in oncology.

摘要

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[2]
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[6]
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[8]
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[2]
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[3]
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[4]
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Cell Insight. 2025-5-23

[5]
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[6]
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