Delivery of MDR1 small interfering RNA by self-complementary recombinant adeno-associated virus vector.
Mol Ther
; 11(4): 523-30, 2005 Apr.
Article
em En
| MEDLINE
| ID: mdl-15771955
ABSTRACT
Small interfering RNAs (siRNAs) are potentially powerful tools for therapeutic gene regulation. DNA cassettes encoding RNA polymerase III promoter-driven hairpin siRNAs allow long-term expression of siRNA in targeted cells. A variety of viral vectors have been used to deliver such cassettes to cells. Here we report on the development and use of a self-complementary recombinant adeno-associated virus (scAAV) vector for siRNA delivery into mammalian cells. We demonstrate that this modified vector efficiently delivers siRNA into multidrug-resistant human breast and oral cancer cells and suppresses MDR1 gene expression. This results in rapid, profound, and durable reduction in the expression of the P-glycoprotein multidrug transporter and a substantial reversion of the drug-resistant phenotype. This research suggests that scAAV-based vectors can be very effective agents for efficient delivery of therapeutic siRNA.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Neoplasias Bucais
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Dependovirus
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP
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Resistencia a Medicamentos Antineoplásicos
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RNA Interferente Pequeno
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Interferência de RNA
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Vetores Genéticos
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article