The role of lipid components in lipid nanoparticles for vaccines and gene therapy
Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt
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The role of lipid components in lipid nanoparticles for vaccines and gene therapy. / Gregersen, Camilla Hald; Kulkarni, Jayesh A.; Witzigmann, Dominik; Lind, Marianne; Petersson, Karsten; Simonsen, Jens B.
I: Advanced Drug Delivery Reviews, Bind 188, 114416, 2022.Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt
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TY - JOUR
T1 - The role of lipid components in lipid nanoparticles for vaccines and gene therapy
AU - Gregersen, Camilla Hald
AU - Kulkarni, Jayesh A.
AU - Witzigmann, Dominik
AU - Lind, Marianne
AU - Petersson, Karsten
AU - Simonsen, Jens B.
N1 - Publisher Copyright: © 2022 Elsevier B.V.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Drug delivery
KW - Helper lipid
KW - Ionizable lipid
KW - Lipid nanoparticles
KW - LNP
KW - Nucleic acid
KW - PEGylated lipid
KW - Physicochemical properties
KW - pK
KW - Targeting
U2 - 10.1016/j.addr.2022.114416
DO - 10.1016/j.addr.2022.114416
M3 - Review
C2 - 35787388
AN - SCOPUS:85134330892
VL - 188
JO - Advanced Drug Delivery Reviews
JF - Advanced Drug Delivery Reviews
SN - 0169-409X
M1 - 114416
ER -
ID: 328237808