Jian Hang Lam , Gaurav Sinsinbar , Ser Yue Loo , Teck Wan Chia , Yan Jun Lee , Jing Yi Fong , Yoong Eng Chia , Rocco Roberto Penna , Shaoqiong Liu , Steve Pascolo , Katherine Schultheis , Madhavan Nallani
{"title":"用于mRNA传递的热稳定性和免疫原性嵌段共聚物纳米颗粒（BNPs）的开发。","authors":"Jian Hang Lam , Gaurav Sinsinbar , Ser Yue Loo , Teck Wan Chia , Yan Jun Lee , Jing Yi Fong , Yoong Eng Chia , Rocco Roberto Penna , Shaoqiong Liu , Steve Pascolo , Katherine Schultheis , Madhavan Nallani","doi":"10.1021/acs.biomac.4c01820","DOIUrl":null,"url":null,"abstract":"<div><div>Combining an amphiphilic block copolymer polybutadiene-<em>b</em>-poly(ethylene glycol) (PBD-<em>b</em>-PEO), an ionizable lipid, a helper lipid, and cholesterol produces thermostable BNPs. Luciferase mRNA-BNPs can be stored for over 1 year at 4 °C with no evidence of degradation to the mRNA or nanocarrier. In vivo, mRNA-BNPs exhibit a greater affinity for secondary lymphoid organs than mRNA-lipid nanoparticles (LNPs) and are efficiently taken up by macrophages and dendritic cells. Freshly fabricated ovalbumin (OVA) mRNA-BNPs elicit robust OVA-specific IgG and functional memory CD8<sup>+</sup> T cells that persist for at least 5 months. Immunogenicity remains intact after 24 weeks of storage at 4 °C. Anti-PEG antibodies are not boosted by the repeated administration of mRNA-BNPs, unlike mRNA-LNPs. Syrian hamsters vaccinated with SARS-CoV-2 spike mRNA-BNPs are protected against weight loss associated with infection and potently suppress pulmonary viral loads. Protective efficacy is comparable to that conferred by a Comirnaty biosimilar. Cumulatively, mRNA-BNPs are thermostable, immunogenic and possess the potential for clinical application.</div></div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (155KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"26 4","pages":"Pages 2444-2457"},"PeriodicalIF":5.4000,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Development of Thermostable and Immunogenic Block Copolymer Nanoparticles (BNPs) for mRNA Delivery\",\"authors\":\"Jian Hang Lam , Gaurav Sinsinbar , Ser Yue Loo , Teck Wan Chia , Yan Jun Lee , Jing Yi Fong , Yoong Eng Chia , Rocco Roberto Penna , Shaoqiong Liu , Steve Pascolo , Katherine Schultheis , Madhavan Nallani\",\"doi\":\"10.1021/acs.biomac.4c01820\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Combining an amphiphilic block copolymer polybutadiene-<em>b</em>-poly(ethylene glycol) (PBD-<em>b</em>-PEO), an ionizable lipid, a helper lipid, and cholesterol produces thermostable BNPs. Luciferase mRNA-BNPs can be stored for over 1 year at 4 °C with no evidence of degradation to the mRNA or nanocarrier. In vivo, mRNA-BNPs exhibit a greater affinity for secondary lymphoid organs than mRNA-lipid nanoparticles (LNPs) and are efficiently taken up by macrophages and dendritic cells. Freshly fabricated ovalbumin (OVA) mRNA-BNPs elicit robust OVA-specific IgG and functional memory CD8<sup>+</sup> T cells that persist for at least 5 months. Immunogenicity remains intact after 24 weeks of storage at 4 °C. Anti-PEG antibodies are not boosted by the repeated administration of mRNA-BNPs, unlike mRNA-LNPs. Syrian hamsters vaccinated with SARS-CoV-2 spike mRNA-BNPs are protected against weight loss associated with infection and potently suppress pulmonary viral loads. Protective efficacy is comparable to that conferred by a Comirnaty biosimilar. Cumulatively, mRNA-BNPs are thermostable, immunogenic and possess the potential for clinical application.</div></div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (155KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div>\",\"PeriodicalId\":30,\"journal\":{\"name\":\"Biomacromolecules\",\"volume\":\"26 4\",\"pages\":\"Pages 2444-2457\"},\"PeriodicalIF\":5.4000,\"publicationDate\":\"2025-04-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomacromolecules\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://www.sciencedirect.com/org/science/article/pii/S1525779725001552\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/3/31 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomacromolecules","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/org/science/article/pii/S1525779725001552","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/31 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Development of Thermostable and Immunogenic Block Copolymer Nanoparticles (BNPs) for mRNA Delivery
Combining an amphiphilic block copolymer polybutadiene-b-poly(ethylene glycol) (PBD-b-PEO), an ionizable lipid, a helper lipid, and cholesterol produces thermostable BNPs. Luciferase mRNA-BNPs can be stored for over 1 year at 4 °C with no evidence of degradation to the mRNA or nanocarrier. In vivo, mRNA-BNPs exhibit a greater affinity for secondary lymphoid organs than mRNA-lipid nanoparticles (LNPs) and are efficiently taken up by macrophages and dendritic cells. Freshly fabricated ovalbumin (OVA) mRNA-BNPs elicit robust OVA-specific IgG and functional memory CD8+ T cells that persist for at least 5 months. Immunogenicity remains intact after 24 weeks of storage at 4 °C. Anti-PEG antibodies are not boosted by the repeated administration of mRNA-BNPs, unlike mRNA-LNPs. Syrian hamsters vaccinated with SARS-CoV-2 spike mRNA-BNPs are protected against weight loss associated with infection and potently suppress pulmonary viral loads. Protective efficacy is comparable to that conferred by a Comirnaty biosimilar. Cumulatively, mRNA-BNPs are thermostable, immunogenic and possess the potential for clinical application.
期刊介绍：
Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine.
Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.
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