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mRNA transfection by a Xentry-protamine cell-penetrating peptide is enhanced by TLR antagonist E6446

Messenger RNA (mRNA) transfection is a developing field that has applications in research and gene therapy. Potentially, mRNA transfection can be mediated efficiently by cell-penetrating peptides (CPPs) as they may be modified to target specific tissues. However, whilst CPPs are well-documented to t...

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Detalles Bibliográficos
Autores principales: Bell, Glenn D., Yang, Yi, Leung, Euphemia, Krissansen, Geoffrey W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066245/
https://www.ncbi.nlm.nih.gov/pubmed/30059522
http://dx.doi.org/10.1371/journal.pone.0201464
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author Bell, Glenn D.
Yang, Yi
Leung, Euphemia
Krissansen, Geoffrey W.
author_facet Bell, Glenn D.
Yang, Yi
Leung, Euphemia
Krissansen, Geoffrey W.
author_sort Bell, Glenn D.
collection PubMed
description Messenger RNA (mRNA) transfection is a developing field that has applications in research and gene therapy. Potentially, mRNA transfection can be mediated efficiently by cell-penetrating peptides (CPPs) as they may be modified to target specific tissues. However, whilst CPPs are well-documented to transfect oligonucleotides and plasmids, mRNA transfection by CPPs has barely been explored. Here we report that peptides, including a truncated form of protamine and the same peptide fused to the CPP Xentry (Xentry-protamine; XP), can transfect mRNAs encoding reporter genes into human cells. Further, this transfection is enhanced by the anti-malarial chloroquine (CQ) and the toll-like receptor antagonist E6446 (6-[3-(pyrrolidin-1-yl)propoxy)-2-(4-(3-(pyrrolidin-1-yl)propoxy)phenyl]benzo[d]oxazole), with E6446 being >5-fold more potent than CQ at enhancing this transfection. Finally, E6446 facilitated the transfection by XP of mRNA encoding the cystic fibrosis transmembrane regulator, the protein mutated in cystic fibrosis. As such, these findings introduce E6446 as a novel transfection enhancer and may be of practical relevance to researchers seeking to improve the mRNA transfection efficiency of their preferred CPP.
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spelling pubmed-60662452018-08-10 mRNA transfection by a Xentry-protamine cell-penetrating peptide is enhanced by TLR antagonist E6446 Bell, Glenn D. Yang, Yi Leung, Euphemia Krissansen, Geoffrey W. PLoS One Research Article Messenger RNA (mRNA) transfection is a developing field that has applications in research and gene therapy. Potentially, mRNA transfection can be mediated efficiently by cell-penetrating peptides (CPPs) as they may be modified to target specific tissues. However, whilst CPPs are well-documented to transfect oligonucleotides and plasmids, mRNA transfection by CPPs has barely been explored. Here we report that peptides, including a truncated form of protamine and the same peptide fused to the CPP Xentry (Xentry-protamine; XP), can transfect mRNAs encoding reporter genes into human cells. Further, this transfection is enhanced by the anti-malarial chloroquine (CQ) and the toll-like receptor antagonist E6446 (6-[3-(pyrrolidin-1-yl)propoxy)-2-(4-(3-(pyrrolidin-1-yl)propoxy)phenyl]benzo[d]oxazole), with E6446 being >5-fold more potent than CQ at enhancing this transfection. Finally, E6446 facilitated the transfection by XP of mRNA encoding the cystic fibrosis transmembrane regulator, the protein mutated in cystic fibrosis. As such, these findings introduce E6446 as a novel transfection enhancer and may be of practical relevance to researchers seeking to improve the mRNA transfection efficiency of their preferred CPP. Public Library of Science 2018-07-30 /pmc/articles/PMC6066245/ /pubmed/30059522 http://dx.doi.org/10.1371/journal.pone.0201464 Text en © 2018 Bell et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Bell, Glenn D.
Yang, Yi
Leung, Euphemia
Krissansen, Geoffrey W.
mRNA transfection by a Xentry-protamine cell-penetrating peptide is enhanced by TLR antagonist E6446
title mRNA transfection by a Xentry-protamine cell-penetrating peptide is enhanced by TLR antagonist E6446
title_full mRNA transfection by a Xentry-protamine cell-penetrating peptide is enhanced by TLR antagonist E6446
title_fullStr mRNA transfection by a Xentry-protamine cell-penetrating peptide is enhanced by TLR antagonist E6446
title_full_unstemmed mRNA transfection by a Xentry-protamine cell-penetrating peptide is enhanced by TLR antagonist E6446
title_short mRNA transfection by a Xentry-protamine cell-penetrating peptide is enhanced by TLR antagonist E6446
title_sort mrna transfection by a xentry-protamine cell-penetrating peptide is enhanced by tlr antagonist e6446
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066245/
https://www.ncbi.nlm.nih.gov/pubmed/30059522
http://dx.doi.org/10.1371/journal.pone.0201464
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