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Biodegradable Polyester Nanoparticle Vaccines Deliver Self-Amplifying mRNA in Mice at Low Doses.
Wilson, David R; Tzeng, Stephany Y; Rui, Yuan; Neshat, Sarah Y; Conge, Marranne J; Luly, Kathryn M; Wang, Ellen; Firestone, Jessica L; McAuliffe, Josie; Maruggi, Giulietta; Jalah, Rashmi; Johnson, Russell; Doloff, Joshua C; Green, Jordan J.
Afiliação
  • Wilson DR; Department of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Tzeng SY; Department of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Rui Y; Department of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Neshat SY; Department of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Conge MJ; Department of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Luly KM; Department of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Wang E; Department of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Firestone JL; GSK Vaccines, Rockville, MD 20850, USA.
  • McAuliffe J; GSK Vaccines, Rockville, MD 20850, USA.
  • Maruggi G; GSK Vaccines, Rockville, MD 20850, USA.
  • Jalah R; GSK Vaccines, Rockville, MD 20850, USA.
  • Johnson R; GSK Vaccines, Rockville, MD 20850, USA.
  • Doloff JC; Department of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Green JJ; Department of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Adv Ther (Weinh) ; 6(5)2023 May.
Article em En | MEDLINE | ID: mdl-37743930
Delivery of self-amplifying mRNA (SAM) has high potential for infectious disease vaccination due its self-adjuvating and dose-sparing properties. Yet a challenge is the susceptibility of SAM to degradation and the need for SAM to reach the cytosol fully intact to enable self-amplification. Lipid nanoparticles have been successfully deployed at incredible speed for mRNA vaccination, but aspects such as cold storage, manufacturing, efficiency of delivery, and the therapeutic window would benefit from further improvement. To investigate alternatives to lipid nanoparticles, we developed a class of >200 biodegradable end-capped lipophilic poly(beta-amino ester)s (PBAEs) that enable efficient delivery of SAM in vitro and in vivo as assessed by measuring expression of SAM encoding reporter proteins. We evaluated the ability of these polymers to deliver SAM intramuscularly in mice, and identified a polymer-based formulation that yielded up to 37-fold higher intramuscular (IM) expression of SAM compared to injected naked SAM. Using the same nanoparticle formulation to deliver a SAM encoding rabies virus glycoprotein, the vaccine elicited superior immunogenicity compared to naked SAM delivery, leading to seroconversion in mice at low RNA injection doses. These biodegradable nanomaterials may be useful in the development of next-generation RNA vaccines for infectious diseases.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Adv Ther (Weinh) Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Adv Ther (Weinh) Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos