In vivo knock-down of multidrug resistance transporters ABCC1 and ABCC2 by AAV-delivered shRNAs and by artificial miRNAs

ABC transporters export clinically-relevant drugs and their over-expression causes multidrug resistance. In order to knock-down ABC transporters, ABCC1 and ABCC2, 13 shRNAs were developed. Four shRNA candidates were tested in vivo using self-complementary adeno-associated virus serotype 8. A strong,...

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Autores principales: Borel, Florie, van Logtenstein, Richard, Koornneef, Annemart, Maczuga, Piotr, Ritsema, Tita, Petry, Harald, van Deventer, Sander JH, Jansen, Peter LM, Konstantinova, Pavlina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Library Publishing Media 2011
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131674/
https://www.ncbi.nlm.nih.gov/pubmed/21769296
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author Borel, Florie
van Logtenstein, Richard
Koornneef, Annemart
Maczuga, Piotr
Ritsema, Tita
Petry, Harald
van Deventer, Sander JH
Jansen, Peter LM
Konstantinova, Pavlina
author_facet Borel, Florie
van Logtenstein, Richard
Koornneef, Annemart
Maczuga, Piotr
Ritsema, Tita
Petry, Harald
van Deventer, Sander JH
Jansen, Peter LM
Konstantinova, Pavlina
author_sort Borel, Florie
collection PubMed
description ABC transporters export clinically-relevant drugs and their over-expression causes multidrug resistance. In order to knock-down ABC transporters, ABCC1 and ABCC2, 13 shRNAs were developed. Four shRNA candidates were tested in vivo using self-complementary adeno-associated virus serotype 8. A strong, specific knock-down of Abbc2 was observed in mice liver, but at the cost of toxicity caused by oversaturation of the RNAi machinery due to high shRNA expression. Subsequent generation of artificial miRNAs showed better efficacy profile. These results demonstrate the feasibility of knocking down Abbc2 via AAV-delivered shRNAs to the liver, and encourage the use of miRNA in further therapeutics development.
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spelling pubmed-31316742011-07-18 In vivo knock-down of multidrug resistance transporters ABCC1 and ABCC2 by AAV-delivered shRNAs and by artificial miRNAs Borel, Florie van Logtenstein, Richard Koornneef, Annemart Maczuga, Piotr Ritsema, Tita Petry, Harald van Deventer, Sander JH Jansen, Peter LM Konstantinova, Pavlina J RNAi Gene Silencing Research Article ABC transporters export clinically-relevant drugs and their over-expression causes multidrug resistance. In order to knock-down ABC transporters, ABCC1 and ABCC2, 13 shRNAs were developed. Four shRNA candidates were tested in vivo using self-complementary adeno-associated virus serotype 8. A strong, specific knock-down of Abbc2 was observed in mice liver, but at the cost of toxicity caused by oversaturation of the RNAi machinery due to high shRNA expression. Subsequent generation of artificial miRNAs showed better efficacy profile. These results demonstrate the feasibility of knocking down Abbc2 via AAV-delivered shRNAs to the liver, and encourage the use of miRNA in further therapeutics development. Library Publishing Media 2011-06-17 /pmc/articles/PMC3131674/ /pubmed/21769296 Text en ©The Authors http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an open access article, published under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/). This license permits non-commercial use, distribution and reproduction of the article, provided the original work is appropriately acknowledged with correct citation details.
spellingShingle Research Article
Borel, Florie
van Logtenstein, Richard
Koornneef, Annemart
Maczuga, Piotr
Ritsema, Tita
Petry, Harald
van Deventer, Sander JH
Jansen, Peter LM
Konstantinova, Pavlina
In vivo knock-down of multidrug resistance transporters ABCC1 and ABCC2 by AAV-delivered shRNAs and by artificial miRNAs
title In vivo knock-down of multidrug resistance transporters ABCC1 and ABCC2 by AAV-delivered shRNAs and by artificial miRNAs
title_full In vivo knock-down of multidrug resistance transporters ABCC1 and ABCC2 by AAV-delivered shRNAs and by artificial miRNAs
title_fullStr In vivo knock-down of multidrug resistance transporters ABCC1 and ABCC2 by AAV-delivered shRNAs and by artificial miRNAs
title_full_unstemmed In vivo knock-down of multidrug resistance transporters ABCC1 and ABCC2 by AAV-delivered shRNAs and by artificial miRNAs
title_short In vivo knock-down of multidrug resistance transporters ABCC1 and ABCC2 by AAV-delivered shRNAs and by artificial miRNAs
title_sort in vivo knock-down of multidrug resistance transporters abcc1 and abcc2 by aav-delivered shrnas and by artificial mirnas
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131674/
https://www.ncbi.nlm.nih.gov/pubmed/21769296
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