{"title":"器官移植中的体外基因治疗:考虑因素和临床转化。","authors":"Michelle Mendiola Pla, Dawn E Bowles","doi":"10.1089/hum.2023.193","DOIUrl":null,"url":null,"abstract":"<p><p><i>Ex vivo</i> machine perfusion (EVMP) is rapidly growing in utility during solid organ transplantation. This form of organ preservation is transforming how organs are allocated and expanding the definition of what is considered a suitable organ for transplantation in comparison with traditional static cold storage. All major organs (heart, lung, liver, kidney) have been influenced by this advanced method of organ preservation. This technology also serves as an unprecedented platform for effective administration of advanced therapeutics, including gene therapies, during organ transplantation to optimize and recondition organs <i>ex vivo</i> in an isolated manner. Applying gene therapy interventions through EVMP introduces different considerations and challenges that are unique from gene therapies designed for systemic administration. Considerations involving vector (choice, dose, toxicity), perfusate composition, and perfusion circuit components should be evaluated when developing a gene therapy to administer in this setting. This review explores these aspects and discusses clinical applications in transplantation where gene therapy interventions can be developed relevant to heart, lung, liver, and kidney donor grafts.</p>","PeriodicalId":13007,"journal":{"name":"Human gene therapy","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11044854/pdf/","citationCount":"0","resultStr":"{\"title\":\"<i>Ex Vivo</i> Gene Therapy in Organ Transplantation: Considerations and Clinical Translation.\",\"authors\":\"Michelle Mendiola Pla, Dawn E Bowles\",\"doi\":\"10.1089/hum.2023.193\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><i>Ex vivo</i> machine perfusion (EVMP) is rapidly growing in utility during solid organ transplantation. This form of organ preservation is transforming how organs are allocated and expanding the definition of what is considered a suitable organ for transplantation in comparison with traditional static cold storage. All major organs (heart, lung, liver, kidney) have been influenced by this advanced method of organ preservation. This technology also serves as an unprecedented platform for effective administration of advanced therapeutics, including gene therapies, during organ transplantation to optimize and recondition organs <i>ex vivo</i> in an isolated manner. Applying gene therapy interventions through EVMP introduces different considerations and challenges that are unique from gene therapies designed for systemic administration. Considerations involving vector (choice, dose, toxicity), perfusate composition, and perfusion circuit components should be evaluated when developing a gene therapy to administer in this setting. This review explores these aspects and discusses clinical applications in transplantation where gene therapy interventions can be developed relevant to heart, lung, liver, and kidney donor grafts.</p>\",\"PeriodicalId\":13007,\"journal\":{\"name\":\"Human gene therapy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11044854/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Human gene therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1089/hum.2023.193\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/30 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human gene therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1089/hum.2023.193","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/30 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
Ex Vivo Gene Therapy in Organ Transplantation: Considerations and Clinical Translation.
Ex vivo machine perfusion (EVMP) is rapidly growing in utility during solid organ transplantation. This form of organ preservation is transforming how organs are allocated and expanding the definition of what is considered a suitable organ for transplantation in comparison with traditional static cold storage. All major organs (heart, lung, liver, kidney) have been influenced by this advanced method of organ preservation. This technology also serves as an unprecedented platform for effective administration of advanced therapeutics, including gene therapies, during organ transplantation to optimize and recondition organs ex vivo in an isolated manner. Applying gene therapy interventions through EVMP introduces different considerations and challenges that are unique from gene therapies designed for systemic administration. Considerations involving vector (choice, dose, toxicity), perfusate composition, and perfusion circuit components should be evaluated when developing a gene therapy to administer in this setting. This review explores these aspects and discusses clinical applications in transplantation where gene therapy interventions can be developed relevant to heart, lung, liver, and kidney donor grafts.
期刊介绍:
Human Gene Therapy is the premier, multidisciplinary journal covering all aspects of gene therapy. The Journal publishes in-depth coverage of DNA, RNA, and cell therapies by delivering the latest breakthroughs in research and technologies. Human Gene Therapy provides a central forum for scientific and clinical information, including ethical, legal, regulatory, social, and commercial issues, which enables the advancement and progress of therapeutic procedures leading to improved patient outcomes, and ultimately, to curing diseases.