Conor A Ruzycki, Derek Montoya, Hammad Irshad, Jason Cox, Yue Zhou, Jacob D McDonald, Philip J Kuehl
{"title":"核酸基因疗法在临床前药物开发中的吸入递送。","authors":"Conor A Ruzycki, Derek Montoya, Hammad Irshad, Jason Cox, Yue Zhou, Jacob D McDonald, Philip J Kuehl","doi":"10.1080/17425247.2023.2261369","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Inhaled gene therapy programs targeting diseases of the lung have seen increasing interest in recent years, though as of yet no product has successfully entered the market. Preclinical research to support such programs is critically important in maximizing the chances of developing successful candidates.</p><p><strong>Areas covered: </strong>Aspects of inhalation delivery of gene therapies are reviewed, with a focus on preclinical research in animal models. Various barriers to inhalation delivery of gene therapies are discussed, including aerosolization stresses, aerosol behavior in the respiratory tract, and disposition processes post-deposition. Important aspects of animal models are considered, including determinations of biologically relevant determinations of dose and issues related to translatability.</p><p><strong>Expert opinion: </strong>Development of clinically-efficacious inhaled gene therapies has proven difficult owing to numerous challenges. Fit-for-purpose experimental and analytical methods are necessary for determinations of biologically relevant doses in preclinical animal models. Further developments in disease-specific animal models may aid in improving the translatability of results in future work, and we expect to see accelerated interests in inhalation gene therapies for various diseases. Sponsors, researchers, and regulators are encouraged to engage in early and frequent discussion regarding candidate therapies, and additional dissemination of preclinical methodologies would be of immense value in avoiding common pitfalls.</p>","PeriodicalId":94004,"journal":{"name":"Expert opinion on drug delivery","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Inhalation delivery of nucleic acid gene therapies in preclinical drug development.\",\"authors\":\"Conor A Ruzycki, Derek Montoya, Hammad Irshad, Jason Cox, Yue Zhou, Jacob D McDonald, Philip J Kuehl\",\"doi\":\"10.1080/17425247.2023.2261369\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Inhaled gene therapy programs targeting diseases of the lung have seen increasing interest in recent years, though as of yet no product has successfully entered the market. Preclinical research to support such programs is critically important in maximizing the chances of developing successful candidates.</p><p><strong>Areas covered: </strong>Aspects of inhalation delivery of gene therapies are reviewed, with a focus on preclinical research in animal models. Various barriers to inhalation delivery of gene therapies are discussed, including aerosolization stresses, aerosol behavior in the respiratory tract, and disposition processes post-deposition. Important aspects of animal models are considered, including determinations of biologically relevant determinations of dose and issues related to translatability.</p><p><strong>Expert opinion: </strong>Development of clinically-efficacious inhaled gene therapies has proven difficult owing to numerous challenges. Fit-for-purpose experimental and analytical methods are necessary for determinations of biologically relevant doses in preclinical animal models. Further developments in disease-specific animal models may aid in improving the translatability of results in future work, and we expect to see accelerated interests in inhalation gene therapies for various diseases. Sponsors, researchers, and regulators are encouraged to engage in early and frequent discussion regarding candidate therapies, and additional dissemination of preclinical methodologies would be of immense value in avoiding common pitfalls.</p>\",\"PeriodicalId\":94004,\"journal\":{\"name\":\"Expert opinion on drug delivery\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Expert opinion on drug delivery\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1080/17425247.2023.2261369\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/10/16 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert opinion on drug delivery","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/17425247.2023.2261369","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/10/16 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
Inhalation delivery of nucleic acid gene therapies in preclinical drug development.
Introduction: Inhaled gene therapy programs targeting diseases of the lung have seen increasing interest in recent years, though as of yet no product has successfully entered the market. Preclinical research to support such programs is critically important in maximizing the chances of developing successful candidates.
Areas covered: Aspects of inhalation delivery of gene therapies are reviewed, with a focus on preclinical research in animal models. Various barriers to inhalation delivery of gene therapies are discussed, including aerosolization stresses, aerosol behavior in the respiratory tract, and disposition processes post-deposition. Important aspects of animal models are considered, including determinations of biologically relevant determinations of dose and issues related to translatability.
Expert opinion: Development of clinically-efficacious inhaled gene therapies has proven difficult owing to numerous challenges. Fit-for-purpose experimental and analytical methods are necessary for determinations of biologically relevant doses in preclinical animal models. Further developments in disease-specific animal models may aid in improving the translatability of results in future work, and we expect to see accelerated interests in inhalation gene therapies for various diseases. Sponsors, researchers, and regulators are encouraged to engage in early and frequent discussion regarding candidate therapies, and additional dissemination of preclinical methodologies would be of immense value in avoiding common pitfalls.