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Optimization of storage conditions for lipid nanoparticle-formulated self-replicating RNA vaccines.
Kim, Byungji; Hosn, Ryan R; Remba, Tanaka; Yun, Dongsoo; Li, Na; Abraham, Wuhbet; Melo, Mariane B; Cortes, Manuel; Li, Bridget; Zhang, Yuebao; Dong, Yizhou; Irvine, Darrell J.
  • Kim B; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Hosn RR; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Remba T; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Yun D; Nanotechnology Materials Core, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Li N; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Abraham W; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Melo MB; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Cortes M; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611, USA.
  • Li B; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Zhang Y; Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States.
  • Dong Y; Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States; Department of Biomedical Engineering, The Center for Clinical and Translational Science, The Comprehensive Cancer Center, Dorothy M. Davis Heart & Lung Research Instit
  • Irvine DJ; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Departments of Biological Engineering and Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of Massachusetts General Hosp
J Control Release ; 353: 241-253, 2022 Nov 30.
Article in English | MEDLINE | ID: covidwho-2231895
ABSTRACT
The recent clinical success of multiple mRNA-based SARS-CoV-2 vaccines has proven the potential of RNA formulated in lipid nanoparticles (LNPs) in humans, and products based on base-modified RNA, sequence-optimized RNA, and self-replicating RNAs formulated in LNPs are all in various stages of clinical development. However, much remains to be learned about critical parameters governing the manufacturing and use of LNP-RNA formulations. One important issue that has received limited attention in the literature to date is the identification of optimal storage conditions for LNP-RNA that preserve long-term activity of the formulations. Here, we analyzed the physical structure, in vivo expression characteristics, and functional activity of alphavirus-derived self-replicating RNA (repRNA)-loaded LNPs encoding HIV vaccine antigens following storage in varying temperatures, buffers, and in the presence or absence of cryoprotectants. We found that for lipid nanoparticles with compositions similar to clinically-used LNPs, storage in RNAse-free PBS containing 10% (w/v) sucrose at -20 °C was able to maintain vaccine stability and in vivo potency at a level equivalent to freshly prepared vaccines following 30 days of storage. LNPs loaded with repRNA could also be lyophilized with retention of bioactivity.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Topics: Vaccines Language: English Journal: J Control Release Journal subject: Pharmacology Year: 2022 Document Type: Article Affiliation country: J.jconrel.2022.11.022

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Topics: Vaccines Language: English Journal: J Control Release Journal subject: Pharmacology Year: 2022 Document Type: Article Affiliation country: J.jconrel.2022.11.022