Emilio Di Ianni, Wataru Obuchi, Koen Breyne, Xandra O. Breakefield
{"title":"Extracellular vesicles for the delivery of gene therapy","authors":"Emilio Di Ianni, Wataru Obuchi, Koen Breyne, Xandra O. Breakefield","doi":"10.1038/s44222-025-00277-7","DOIUrl":null,"url":null,"abstract":"Gene therapy has brought hope for the treatment of previously incurable diseases, such as genetic disorders, cancers and autoimmune diseases. However, gene therapy requires efficient delivery with cell and tissue specificity, which remains challenging owing to the limited targeting and cargo-loading capacity of viral delivery vehicles, as well as immunogenicity and toxicity concerns. Extracellular vesicles can be designed as non-viral carriers for gene therapy owing to their ability to deliver multiple cargo types, including transgenes, small encoding or non-coding RNA, DNA and functional proteins. Importantly, extracellular vesicles are immunologically neutral and can cross biological barriers. In this Review, we discuss the application of extracellular vesicles in gene therapy. We outline how the inherent content of extracellular vesicles can facilitate different gene-therapy approaches and examine the design of extracellular vesicles for the loading of gene-therapy tools, targeted delivery and cargo release. Finally, we survey clinical applications of extracellular vesicles and highlight important engineering and translational challenges. Extracellular vesicles can be designed to serve as delivery platforms for gene therapy. This Review discusses the application and engineering of extracellular vesicles for different gene-therapy modalities, outlining crucial steps to advance this technology into the clinic.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"3 5","pages":"360-373"},"PeriodicalIF":37.6000,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature reviews bioengineering","FirstCategoryId":"1085","ListUrlMain":"https://www.nature.com/articles/s44222-025-00277-7","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Gene therapy has brought hope for the treatment of previously incurable diseases, such as genetic disorders, cancers and autoimmune diseases. However, gene therapy requires efficient delivery with cell and tissue specificity, which remains challenging owing to the limited targeting and cargo-loading capacity of viral delivery vehicles, as well as immunogenicity and toxicity concerns. Extracellular vesicles can be designed as non-viral carriers for gene therapy owing to their ability to deliver multiple cargo types, including transgenes, small encoding or non-coding RNA, DNA and functional proteins. Importantly, extracellular vesicles are immunologically neutral and can cross biological barriers. In this Review, we discuss the application of extracellular vesicles in gene therapy. We outline how the inherent content of extracellular vesicles can facilitate different gene-therapy approaches and examine the design of extracellular vesicles for the loading of gene-therapy tools, targeted delivery and cargo release. Finally, we survey clinical applications of extracellular vesicles and highlight important engineering and translational challenges. Extracellular vesicles can be designed to serve as delivery platforms for gene therapy. This Review discusses the application and engineering of extracellular vesicles for different gene-therapy modalities, outlining crucial steps to advance this technology into the clinic.