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Optimization of Lipid Nanoformulations for Effective mRNA Delivery
by
Ren, Xuan
, Han, TiYun
, Chen, Huiling
, Zhang, Dekui
, Xu, Shi
in
2-dioleoyl-3-trimethylammonium-propane
/ 2-dioleoyl-sn-glycero-3-phosphoethanolamine
/ Acids
/ Antigens
/ Aqueous solutions
/ China
/ Cholesterol
/ Clinical trials
/ Coronaviruses
/ COVID-19
/ Delayed-Action Preparations
/ Efficiency
/ Epidemics
/ Fatty Acids, Monounsaturated
/ Gene expression
/ Gene therapy
/ Genes
/ Humans
/ Laboratory animals
/ lipid nanoparticles
/ Lipids
/ Liposomes
/ Messenger RNA
/ mRNA delivery
/ mRNA Vaccines
/ Nanoparticles
/ Original Research
/ Polyethylene glycol
/ Quaternary Ammonium Compounds
/ RNA, Messenger - genetics
/ Vaccines
/ Vaccines, Synthetic
2022
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Optimization of Lipid Nanoformulations for Effective mRNA Delivery
by
Ren, Xuan
, Han, TiYun
, Chen, Huiling
, Zhang, Dekui
, Xu, Shi
in
2-dioleoyl-3-trimethylammonium-propane
/ 2-dioleoyl-sn-glycero-3-phosphoethanolamine
/ Acids
/ Antigens
/ Aqueous solutions
/ China
/ Cholesterol
/ Clinical trials
/ Coronaviruses
/ COVID-19
/ Delayed-Action Preparations
/ Efficiency
/ Epidemics
/ Fatty Acids, Monounsaturated
/ Gene expression
/ Gene therapy
/ Genes
/ Humans
/ Laboratory animals
/ lipid nanoparticles
/ Lipids
/ Liposomes
/ Messenger RNA
/ mRNA delivery
/ mRNA Vaccines
/ Nanoparticles
/ Original Research
/ Polyethylene glycol
/ Quaternary Ammonium Compounds
/ RNA, Messenger - genetics
/ Vaccines
/ Vaccines, Synthetic
2022
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Do you wish to request the book?
Optimization of Lipid Nanoformulations for Effective mRNA Delivery
by
Ren, Xuan
, Han, TiYun
, Chen, Huiling
, Zhang, Dekui
, Xu, Shi
in
2-dioleoyl-3-trimethylammonium-propane
/ 2-dioleoyl-sn-glycero-3-phosphoethanolamine
/ Acids
/ Antigens
/ Aqueous solutions
/ China
/ Cholesterol
/ Clinical trials
/ Coronaviruses
/ COVID-19
/ Delayed-Action Preparations
/ Efficiency
/ Epidemics
/ Fatty Acids, Monounsaturated
/ Gene expression
/ Gene therapy
/ Genes
/ Humans
/ Laboratory animals
/ lipid nanoparticles
/ Lipids
/ Liposomes
/ Messenger RNA
/ mRNA delivery
/ mRNA Vaccines
/ Nanoparticles
/ Original Research
/ Polyethylene glycol
/ Quaternary Ammonium Compounds
/ RNA, Messenger - genetics
/ Vaccines
/ Vaccines, Synthetic
2022
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Optimization of Lipid Nanoformulations for Effective mRNA Delivery
Journal Article
Optimization of Lipid Nanoformulations for Effective mRNA Delivery
2022
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Overview
Since the coronavirus disease 2019 (COVID-19) pandemic, the value of mRNA vaccine has been widely recognized worldwide. Messenger RNA (mRNA) therapy platform provides a promising alternative to DNA delivery in non-viral gene therapy. Lipid nanoparticles (LNPs), as effective mRNA delivery carriers, have been highly valued by the pharmaceutical industry, and many LNPs have entered clinical trials.
We developed an ideal lipid nanoformulation, named LNP3, composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and cholesterol, and observed its release efficiency, sustained release, organ specific targeting and thermal stability.
In vitro studies showed that the transfection efficiency of LNP3 was higher than that of LNPs composed of DOTAP-DOPE and DOTAP-cholesterol. The positive to negative charge ratio of LNPs is a determinant of mRNA transfer efficiency in different cell lines. We noted that the buffer affected the packaging of mRNA LNPs and identified sodium potassium magnesium calcium and glucose solution (SPMCG) as a favorable buffer formulation. LNP3 suspension can be lyophilized into a thermally stable formulation to maintain activity after rehydration both in vitro and in vivo. Finally, LNP3 showed sustained release and organ specific targeting.
We have developed an ideal lipid nanoformulation composed of DOTAP, DOPE and cholesterol for effective mRNA delivery.
Publisher
Dove Medical Press Limited,Taylor & Francis Ltd,Dove Press,Dove,Dove Medical Press
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