PMID- 36986843 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230331 IS - 1999-4923 (Print) IS - 1999-4923 (Electronic) IS - 1999-4923 (Linking) VI - 15 IP - 3 DP - 2023 Mar 18 TI - The CRISPR/Cas9 System Delivered by Extracellular Vesicles. LID - 10.3390/pharmaceutics15030984 [doi] LID - 984 AB - Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas) systems can precisely manipulate DNA sequences to change the characteristics of cells and organs, which has potential in the mechanistic research on genes and the treatment of diseases. However, clinical applications are restricted by the lack of safe, targeted and effective delivery vectors. Extracellular vesicles (EVs) are an attractive delivery platform for CRISPR/Cas9. Compared with viral and other vectors, EVs present several advantages, including safety, protection, capacity, penetrating ability, targeting ability and potential for modification. Consequently, EVs are profitably used to deliver the CRISPR/Cas9 in vivo. In this review, the advantages and disadvantages of the delivery form and vectors of the CRISPR/Cas9 are concluded. The favorable traits of EVs as vectors, such as the innate characteristics, physiological and pathological functions, safety and targeting ability of EVs, are summarized. Furthermore, in terms of the delivery of the CRISPR/Cas9 by EVs, EV sources and isolation strategies, the delivery form and loading methods of the CRISPR/Cas9 and applications have been concluded and discussed. Finally, this review provides future directions of EVs as vectors of the CRISPR/Cas9 system in clinical applications, such as the safety, capacity, consistent quality, yield and targeting ability of EVs. FAU - Zhu, Xinglong AU - Zhu X AUID- ORCID: 0000-0002-2537-731X AD - Key Laboratory of Transplant Engineering and Immunology, Institute of Clinical Pathology, West China Hospital, Sichuan University, Chengdu 610041, China. FAU - Gao, Mengyu AU - Gao M AUID- ORCID: 0000-0003-0269-9727 AD - Key Laboratory of Transplant Engineering and Immunology, Institute of Clinical Pathology, West China Hospital, Sichuan University, Chengdu 610041, China. FAU - Yang, Yongfeng AU - Yang Y AUID- ORCID: 0000-0002-8109-9801 AD - Institute of Respiratory Health, West China Hospital, Sichuan University, Chengdu 610041, China. AD - Precision Medicine Key Laboratory, West China Hospital, Sichuan University, Chengdu 610041, China. FAU - Li, Weimin AU - Li W AUID- ORCID: 0000-0003-0985-0311 AD - Institute of Respiratory Health, West China Hospital, Sichuan University, Chengdu 610041, China. AD - Precision Medicine Key Laboratory, West China Hospital, Sichuan University, Chengdu 610041, China. AD - Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, China. FAU - Bao, Ji AU - Bao J AUID- ORCID: 0000-0001-8413-3270 AD - Key Laboratory of Transplant Engineering and Immunology, Institute of Clinical Pathology, West China Hospital, Sichuan University, Chengdu 610041, China. FAU - Li, Yi AU - Li Y AUID- ORCID: 0000-0001-8661-4617 AD - Institute of Respiratory Health, West China Hospital, Sichuan University, Chengdu 610041, China. AD - Precision Medicine Key Laboratory, West China Hospital, Sichuan University, Chengdu 610041, China. LA - eng GR - 81900574/National Natural Scientific Foundations of China/ GR - 82200078/National Natural Scientific Foundations of China/ GR - 2018HXBH041/Post-Doctor Research Project, West China Hospital, Sichuan University, Grant/Award/ PT - Journal Article PT - Review DEP - 20230318 PL - Switzerland TA - Pharmaceutics JT - Pharmaceutics JID - 101534003 PMC - PMC10053467 OTO - NOTNLM OT - CRISPR/Cas9 OT - biomedical applications OT - delivery OT - extracellular vesicles COIS- The authors declare no competing interests. EDAT- 2023/03/30 06:00 MHDA- 2023/03/30 06:01 PMCR- 2023/03/18 CRDT- 2023/03/29 02:03 PHST- 2023/02/17 00:00 [received] PHST- 2023/03/14 00:00 [revised] PHST- 2023/03/17 00:00 [accepted] PHST- 2023/03/30 06:01 [medline] PHST- 2023/03/29 02:03 [entrez] PHST- 2023/03/30 06:00 [pubmed] PHST- 2023/03/18 00:00 [pmc-release] AID - pharmaceutics15030984 [pii] AID - pharmaceutics-15-00984 [pii] AID - 10.3390/pharmaceutics15030984 [doi] PST - epublish SO - Pharmaceutics. 2023 Mar 18;15(3):984. doi: 10.3390/pharmaceutics15030984.