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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Detalles Bibliográficos
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
Descripción
Sumario: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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