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已发表论文

脂质纳米制剂的优化以实现有效的 mRNA 传递

 

Authors Chen H , Ren X, Xu S, Zhang D, Han T

Received 7 March 2022

Accepted for publication 24 June 2022

Published 2 July 2022 Volume 2022:17 Pages 2893—2905

DOI https://doi.org/10.2147/IJN.S363990

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Farooq A. Shiekh

Introduction: 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.
Methods: 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.
Results: 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.
Conclusion: We have developed an ideal lipid nanoformulation composed of DOTAP, DOPE and cholesterol for effective mRNA delivery.
Keywords: lipid nanoparticles, mRNA delivery, 1,2-dioleoyl-3-trimethylammonium-propane, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, cholesterol