AI Article Synopsis
- ABC transporters, specifically ABCC1 and ABCC2, contribute to drug resistance when over-expressed, leading to challenges in treating certain conditions.
- Researchers developed 13 shRNAs to target and knock down these transporters, with promising results from four shRNA candidates tested in mice using a specific viral delivery method.
- While strong knock-down of Abbc2 in the liver was achieved, it resulted in toxicity due to high levels of shRNA; however, subsequent artificial miRNAs showed improved effectiveness and safety, encouraging further use in therapeutic development.
Article Abstract
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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131674 | PMC |
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