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 hyperresp...
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| Published in | Biotechnology and bioprocess engineering Vol. 29; no. 1; pp. 97 - 108 |
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| Main Authors | , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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Seoul
The Korean Society for Biotechnology and Bioengineering
01.02.2024
Springer Nature B.V 한국생물공학회 |
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| Abstract | 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.
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| AbstractList | 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. KCI Citation Count: 0 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. Graphical abstract 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. |
| Author | Jung, Jae Wook Heo, Seoyoun Lee, Sang-Kyung Yi, Yujong Rhim, Taiyoun Choi, Hyo Sung Chung, Kunho Choi, Changseon Yoon, Ho Joo Ullah, Irfan Yun, Gyeongju Kim, Sang-Heon Kang, Eunhwa |
| Author_xml | – sequence: 1 givenname: Irfan surname: Ullah fullname: Ullah, Irfan organization: Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Deparment of Internal Medicine, Yale University – sequence: 2 givenname: Hyo Sung surname: Choi fullname: Choi, Hyo Sung organization: Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University – sequence: 3 givenname: Changseon surname: Choi fullname: Choi, Changseon organization: Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Deptarment of Pharmacology, School of Medicine, Yale University – sequence: 4 givenname: Kunho surname: Chung fullname: Chung, Kunho organization: Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Lerner Research Institute, Cleveland Clinic – sequence: 5 givenname: Jae Wook surname: Jung fullname: Jung, Jae Wook organization: Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University – sequence: 6 givenname: Gyeongju surname: Yun fullname: Yun, Gyeongju organization: Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University – sequence: 7 givenname: Seoyoun surname: Heo fullname: Heo, Seoyoun organization: Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University – sequence: 8 givenname: Yujong surname: Yi fullname: Yi, Yujong organization: Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University – sequence: 9 givenname: Eunhwa surname: Kang fullname: Kang, Eunhwa organization: Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University – sequence: 10 givenname: Sang-Heon surname: Kim fullname: Kim, Sang-Heon organization: Department of Internal Medicine, Hanyang University School of Medicine – sequence: 11 givenname: Ho Joo surname: Yoon fullname: Yoon, Ho Joo organization: Department of Internal Medicine, Hanyang University School of Medicine – sequence: 12 givenname: Taiyoun surname: Rhim fullname: Rhim, Taiyoun email: rhim@hanyang.ac.kr organization: Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University – sequence: 13 givenname: Sang-Kyung surname: Lee fullname: Lee, Sang-Kyung email: sangkyunglee@hanyang.ac.kr organization: Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University |
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| Keywords | siRNA delivery Lung epithelial cells Rabies virus glycoprotein Airway inflammation Interleukin-4 receptor alpha Asthma |
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| Snippet | Asthma is a chronic inflammatory disease triggered by allergic reactions in the bronchia. These reactions lead to swelling of mucous membranes, hypersecretion... |
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| SubjectTerms | Allergic reactions Allergies Asthma Biotechnology Bronchoconstriction Chemistry Chemistry and Materials Science cysteine Epithelial cells Epithelium gene targeting Glycoproteins hypersecretion Industrial and Production Engineering Inflammation Inflammatory diseases Interleukin 13 Interleukin 4 Lungs Lymphocytes T Lyssavirus mice Mucus Ovalbumin Peptides Rabies Rabies lyssavirus Receptors Research Paper Respiratory tract diseases siRNA therapeutics 생물공학 |
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| Title | Targeted siRNA delivery to lung epithelia reduces airway inflammation in a mouse model of allergic asthma |
| URI | https://link.springer.com/article/10.1007/s12257-024-00027-3 https://www.proquest.com/docview/2933288274 https://www.proquest.com/docview/3153623073 https://www.kci.go.kr/kciportal/ci/sereArticleSearch/ciSereArtiView.kci?sereArticleSearchBean.artiId=ART003060261 |
| Volume | 29 |
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| ispartofPNX | Biotechnology and Bioprocess Engineering, 2024, 29(1), , pp.97-108 |
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