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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
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. |
format | Online Article Text |
id | pubmed-4768262 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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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