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Targeted delivery of antisense oligonucleotides to pancreatic β-cells
Antisense oligonucleotide (ASO) silencing of the expression of disease-associated genes is an attractive novel therapeutic approach, but treatments are limited by the ability to deliver ASOs to cells and tissues. Following systemic administration, ASOs preferentially accumulate in liver and kidney....
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192685/ https://www.ncbi.nlm.nih.gov/pubmed/30345352 http://dx.doi.org/10.1126/sciadv.aat3386 |
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author | Ämmälä, C. Drury, W. J. Knerr, L. Ahlstedt, I. Stillemark-Billton, P. Wennberg-Huldt, C. Andersson, E.-M. Valeur, E. Jansson-Löfmark, R. Janzén, D. Sundström, L. Meuller, J. Claesson, J. Andersson, P. Johansson, C. Lee, R. G. Prakash, T. P. Seth, P. P. Monia, B. P. Andersson, S. |
author_facet | Ämmälä, C. Drury, W. J. Knerr, L. Ahlstedt, I. Stillemark-Billton, P. Wennberg-Huldt, C. Andersson, E.-M. Valeur, E. Jansson-Löfmark, R. Janzén, D. Sundström, L. Meuller, J. Claesson, J. Andersson, P. Johansson, C. Lee, R. G. Prakash, T. P. Seth, P. P. Monia, B. P. Andersson, S. |
author_sort | Ämmälä, C. |
collection | PubMed |
description | Antisense oligonucleotide (ASO) silencing of the expression of disease-associated genes is an attractive novel therapeutic approach, but treatments are limited by the ability to deliver ASOs to cells and tissues. Following systemic administration, ASOs preferentially accumulate in liver and kidney. Among the cell types refractory to ASO uptake is the pancreatic insulin-secreting β-cell. Here, we show that conjugation of ASOs to a ligand of the glucagon-like peptide-1 receptor (GLP1R) can productively deliver ASO cargo to pancreatic β-cells both in vitro and in vivo. Ligand-conjugated ASOs silenced target genes in pancreatic islets at doses that did not affect target gene expression in liver or other tissues, indicating enhanced tissue and cell type specificity. This finding has potential to broaden the use of ASO technology, opening up novel therapeutic opportunities, and presents an innovative approach for targeted delivery of ASOs to additional cell types. |
format | Online Article Text |
id | pubmed-6192685 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-61926852018-10-19 Targeted delivery of antisense oligonucleotides to pancreatic β-cells Ämmälä, C. Drury, W. J. Knerr, L. Ahlstedt, I. Stillemark-Billton, P. Wennberg-Huldt, C. Andersson, E.-M. Valeur, E. Jansson-Löfmark, R. Janzén, D. Sundström, L. Meuller, J. Claesson, J. Andersson, P. Johansson, C. Lee, R. G. Prakash, T. P. Seth, P. P. Monia, B. P. Andersson, S. Sci Adv Research Articles Antisense oligonucleotide (ASO) silencing of the expression of disease-associated genes is an attractive novel therapeutic approach, but treatments are limited by the ability to deliver ASOs to cells and tissues. Following systemic administration, ASOs preferentially accumulate in liver and kidney. Among the cell types refractory to ASO uptake is the pancreatic insulin-secreting β-cell. Here, we show that conjugation of ASOs to a ligand of the glucagon-like peptide-1 receptor (GLP1R) can productively deliver ASO cargo to pancreatic β-cells both in vitro and in vivo. Ligand-conjugated ASOs silenced target genes in pancreatic islets at doses that did not affect target gene expression in liver or other tissues, indicating enhanced tissue and cell type specificity. This finding has potential to broaden the use of ASO technology, opening up novel therapeutic opportunities, and presents an innovative approach for targeted delivery of ASOs to additional cell types. American Association for the Advancement of Science 2018-10-17 /pmc/articles/PMC6192685/ /pubmed/30345352 http://dx.doi.org/10.1126/sciadv.aat3386 Text en Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Ämmälä, C. Drury, W. J. Knerr, L. Ahlstedt, I. Stillemark-Billton, P. Wennberg-Huldt, C. Andersson, E.-M. Valeur, E. Jansson-Löfmark, R. Janzén, D. Sundström, L. Meuller, J. Claesson, J. Andersson, P. Johansson, C. Lee, R. G. Prakash, T. P. Seth, P. P. Monia, B. P. Andersson, S. Targeted delivery of antisense oligonucleotides to pancreatic β-cells |
title | Targeted delivery of antisense oligonucleotides to pancreatic β-cells |
title_full | Targeted delivery of antisense oligonucleotides to pancreatic β-cells |
title_fullStr | Targeted delivery of antisense oligonucleotides to pancreatic β-cells |
title_full_unstemmed | Targeted delivery of antisense oligonucleotides to pancreatic β-cells |
title_short | Targeted delivery of antisense oligonucleotides to pancreatic β-cells |
title_sort | targeted delivery of antisense oligonucleotides to pancreatic β-cells |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192685/ https://www.ncbi.nlm.nih.gov/pubmed/30345352 http://dx.doi.org/10.1126/sciadv.aat3386 |
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