Irfan Ullah, Hyo Sung Choi, Changseon Choi, Kunho Chung, Jae Wook Jung, Gyeongju Yun, Seoyoun Heo, Yujong Yi, Eunhwa Kang, Sang-Heon Kim, Ho Joo Yoon, Taiyoun Rhim, Sang-Kyung Lee
{"title":"在过敏性哮喘小鼠模型中,靶向 siRNA 运送到肺上皮细胞可减少气道炎症","authors":"Irfan Ullah, Hyo Sung Choi, Changseon Choi, Kunho Chung, Jae Wook Jung, Gyeongju Yun, Seoyoun Heo, Yujong Yi, Eunhwa Kang, Sang-Heon Kim, Ho Joo Yoon, Taiyoun Rhim, Sang-Kyung Lee","doi":"10.1007/s12257-024-00027-3","DOIUrl":null,"url":null,"abstract":"<p>Asthma is a chronic inflammatory disease triggered by allergic reactions in the bronchia. These reactions lead to swelling of mucous membranes, hypersecretion of mucus, and bronchoconstriction, resulting in a restricted opening of the lung airway. Allergic pulmonary inflammation and airway hyperresponsiveness are induced when Th2 cytokines, such as interleukin (IL)-4 and IL-13, bind to their cognate receptors on lung epithelial cells. Specifically, IL-13 stimulates inflammation through a multi-subunit receptor, mainly the alpha chain of the IL-4 receptor (IL-4Rα), which also plays a role in IL-4 signaling. In this study, we employed a lung epithelial cell-targeting siRNA carrier composed of a rabies virus glycoprotein-derived small peptide coupled with cationic nona-arginine and trileucine before cysteine peptide (RVG9R3LC). This carrier was complexed with siRNA, enabling targeted delivery of therapeutic siRNA to IL-4Rα (siIL4Rα) expressed in lung epithelial cells within an asthma model in vivo. Our approach demonstrated efficient gene knockdown in cultured lung epithelial cells and in vivo. Furthermore, two administrations of therapeutic siIL4Rα protected the ovalbumin-sensitized and challenged asthma mouse model from airway inflammation and excessive mucus secretion. Our findings suggest that the peptide-siRNA carrier system presents a promising therapeutic approach for respiratory inflammation.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3>","PeriodicalId":8936,"journal":{"name":"Biotechnology and Bioprocess Engineering","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Targeted siRNA delivery to lung epithelia reduces airway inflammation in a mouse model of allergic asthma\",\"authors\":\"Irfan Ullah, Hyo Sung Choi, Changseon Choi, Kunho Chung, Jae Wook Jung, Gyeongju Yun, Seoyoun Heo, Yujong Yi, Eunhwa Kang, Sang-Heon Kim, Ho Joo Yoon, Taiyoun Rhim, Sang-Kyung Lee\",\"doi\":\"10.1007/s12257-024-00027-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Asthma is a chronic inflammatory disease triggered by allergic reactions in the bronchia. 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Our approach demonstrated efficient gene knockdown in cultured lung epithelial cells and in vivo. Furthermore, two administrations of therapeutic siIL4Rα protected the ovalbumin-sensitized and challenged asthma mouse model from airway inflammation and excessive mucus secretion. 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Targeted siRNA delivery to lung epithelia reduces airway inflammation in a mouse model of allergic asthma
Asthma is a chronic inflammatory disease triggered by allergic reactions in the bronchia. These reactions lead to swelling of mucous membranes, hypersecretion of mucus, and bronchoconstriction, resulting in a restricted opening of the lung airway. Allergic pulmonary inflammation and airway hyperresponsiveness are induced when Th2 cytokines, such as interleukin (IL)-4 and IL-13, bind to their cognate receptors on lung epithelial cells. Specifically, IL-13 stimulates inflammation through a multi-subunit receptor, mainly the alpha chain of the IL-4 receptor (IL-4Rα), which also plays a role in IL-4 signaling. In this study, we employed a lung epithelial cell-targeting siRNA carrier composed of a rabies virus glycoprotein-derived small peptide coupled with cationic nona-arginine and trileucine before cysteine peptide (RVG9R3LC). This carrier was complexed with siRNA, enabling targeted delivery of therapeutic siRNA to IL-4Rα (siIL4Rα) expressed in lung epithelial cells within an asthma model in vivo. Our approach demonstrated efficient gene knockdown in cultured lung epithelial cells and in vivo. Furthermore, two administrations of therapeutic siIL4Rα protected the ovalbumin-sensitized and challenged asthma mouse model from airway inflammation and excessive mucus secretion. Our findings suggest that the peptide-siRNA carrier system presents a promising therapeutic approach for respiratory inflammation.
期刊介绍:
Biotechnology and Bioprocess Engineering is an international bimonthly journal published by the Korean Society for Biotechnology and Bioengineering. BBE is devoted to the advancement in science and technology in the wide area of biotechnology, bioengineering, and (bio)medical engineering. This includes but is not limited to applied molecular and cell biology, engineered biocatalysis and biotransformation, metabolic engineering and systems biology, bioseparation and bioprocess engineering, cell culture technology, environmental and food biotechnology, pharmaceutics and biopharmaceutics, biomaterials engineering, nanobiotechnology, and biosensor and bioelectronics.