Development of Thermostable and Immunogenic Block Copolymer Nanoparticles (BNPs) for mRNA Delivery.

IF 5.5 2区 化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
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
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引用次数: 0

Abstract

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.

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来源期刊
Biomacromolecules
Biomacromolecules 化学-高分子科学
CiteScore
10.60
自引率
4.80%
发文量
417
审稿时长
1.6 months
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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