Effects of local structural transformation of lipid-like compounds on delivery of messenger RNA

Lipid-like nanoparticles (LLNs) have shown great potential for RNA delivery. Lipid-like compounds are key components in LLNs. In this study, we investigated the effects of local structural transformation of lipid-like compounds on delivery of messenger RNA. Our results showed that position change of...

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Detalles Bibliográficos
Autores principales: Li, Bin, Luo, Xiao, Deng, Binbin, Giancola, JoLynn B., McComb, David W., Schmittgen, Thomas D., Dong, Yizhou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768262/
https://www.ncbi.nlm.nih.gov/pubmed/26916931
http://dx.doi.org/10.1038/srep22137
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author Li, Bin
Luo, Xiao
Deng, Binbin
Giancola, JoLynn B.
McComb, David W.
Schmittgen, Thomas D.
Dong, Yizhou
author_facet Li, Bin
Luo, Xiao
Deng, Binbin
Giancola, JoLynn B.
McComb, David W.
Schmittgen, Thomas D.
Dong, Yizhou
author_sort Li, Bin
collection PubMed
description Lipid-like nanoparticles (LLNs) have shown great potential for RNA delivery. Lipid-like compounds are key components in LLNs. In this study, we investigated the effects of local structural transformation of lipid-like compounds on delivery of messenger RNA. Our results showed that position change of functional groups on lipid-like compounds can dramatically improve delivery efficiency. We then optimized formulation ratios of TNT-b(10) LLNs, a lead material, increasing delivery efficiency over 2-fold. More importantly, pegylated TNT-b(10) LLNs is stable for over four weeks and is over 10-fold more efficient than that of its counterpart TNT-a(10) LLNs. Additionally, the optimal formulation O-TNT-b(10) LLNs is capable of delivering mRNA encoding luciferase in vivo. These results provide useful insights into the design of next generation LLNs for mRNA delivery.
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spelling pubmed-47682622016-03-02 Effects of local structural transformation of lipid-like compounds on delivery of messenger RNA Li, Bin Luo, Xiao Deng, Binbin Giancola, JoLynn B. McComb, David W. Schmittgen, Thomas D. Dong, Yizhou Sci Rep Article Lipid-like nanoparticles (LLNs) have shown great potential for RNA delivery. Lipid-like compounds are key components in LLNs. In this study, we investigated the effects of local structural transformation of lipid-like compounds on delivery of messenger RNA. Our results showed that position change of functional groups on lipid-like compounds can dramatically improve delivery efficiency. We then optimized formulation ratios of TNT-b(10) LLNs, a lead material, increasing delivery efficiency over 2-fold. More importantly, pegylated TNT-b(10) LLNs is stable for over four weeks and is over 10-fold more efficient than that of its counterpart TNT-a(10) LLNs. Additionally, the optimal formulation O-TNT-b(10) LLNs is capable of delivering mRNA encoding luciferase in vivo. These results provide useful insights into the design of next generation LLNs for mRNA delivery. Nature Publishing Group 2016-02-26 /pmc/articles/PMC4768262/ /pubmed/26916931 http://dx.doi.org/10.1038/srep22137 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Li, Bin
Luo, Xiao
Deng, Binbin
Giancola, JoLynn B.
McComb, David W.
Schmittgen, Thomas D.
Dong, Yizhou
Effects of local structural transformation of lipid-like compounds on delivery of messenger RNA
title Effects of local structural transformation of lipid-like compounds on delivery of messenger RNA
title_full Effects of local structural transformation of lipid-like compounds on delivery of messenger RNA
title_fullStr Effects of local structural transformation of lipid-like compounds on delivery of messenger RNA
title_full_unstemmed Effects of local structural transformation of lipid-like compounds on delivery of messenger RNA
title_short Effects of local structural transformation of lipid-like compounds on delivery of messenger RNA
title_sort effects of local structural transformation of lipid-like compounds on delivery of messenger rna
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768262/
https://www.ncbi.nlm.nih.gov/pubmed/26916931
http://dx.doi.org/10.1038/srep22137
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