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The role of lipid components in lipid nanoparticles for vaccines and gene therapy.
Hald Albertsen, Camilla; Kulkarni, Jayesh A; Witzigmann, Dominik; Lind, Marianne; Petersson, Karsten; Simonsen, Jens B.
  • Hald Albertsen C; Explorative Formulation & Technologies, CMC Design and Development, LEO Pharma A/S, Industriparken 55, 2750 Ballerup, Denmark.
  • Kulkarni JA; NanoVation Therapeutics Inc., 2405 Wesbrook Mall, 4th Floor, Vancouver BC V6T 1Z3, Canada.
  • Witzigmann D; NanoVation Therapeutics Inc., 2405 Wesbrook Mall, 4th Floor, Vancouver BC V6T 1Z3, Canada.
  • Lind M; Explorative Formulation & Technologies, CMC Design and Development, LEO Pharma A/S, Industriparken 55, 2750 Ballerup, Denmark.
  • Petersson K; Explorative Formulation & Technologies, CMC Design and Development, LEO Pharma A/S, Industriparken 55, 2750 Ballerup, Denmark.
  • Simonsen JB; Explorative Formulation & Technologies, CMC Design and Development, LEO Pharma A/S, Industriparken 55, 2750 Ballerup, Denmark. Electronic address: jebsm@leo-pharma.com.
Adv Drug Deliv Rev ; 188: 114416, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1914095
ABSTRACT
Lipid nanoparticles (LNPs) play an important role in mRNA vaccines against COVID-19. In addition, many preclinical and clinical studies, including the siRNA-LNP product, Onpattro®, highlight that LNPs unlock the potential of nucleic acid-based therapies and vaccines. To understand what is key to the success of LNPs, we need to understand the role of the building blocks that constitute them. In this Review, we discuss what each lipid component adds to the LNP delivery platform in terms of size, structure, stability, apparent pKa, nucleic acid encapsulation efficiency, cellular uptake, and endosomal escape. To explore this, we present findings from the liposome field as well as from landmark and recent articles in the LNP literature. We also discuss challenges and strategies related to in vitro/in vivo studies of LNPs based on fluorescence readouts, immunogenicity/reactogenicity, and LNP delivery beyond the liver. How these fundamental challenges are pursued, including what lipid components are added and combined, will likely determine the scope of LNP-based gene therapies and vaccines for treating various diseases.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Vaccines / Nucleic Acids / Nanoparticles / COVID-19 Type of study: Prognostic study Topics: Vaccines Limits: Humans Language: English Journal: Adv Drug Deliv Rev Journal subject: Pharmacology / Drug Therapy Year: 2022 Document Type: Article Affiliation country: J.addr.2022.114416

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Vaccines / Nucleic Acids / Nanoparticles / COVID-19 Type of study: Prognostic study Topics: Vaccines Limits: Humans Language: English Journal: Adv Drug Deliv Rev Journal subject: Pharmacology / Drug Therapy Year: 2022 Document Type: Article Affiliation country: J.addr.2022.114416