Why the study?
Does AAV6-mediated shRNA against PLB safely knock down PLB expression in healthy canines?
Population
11 healthy canines (dogs)
Comparison
Self-complementary adeno-associated virus… vs Empty AAV6 capsid or scAAV6 expressing dominant…
Design
Preclinical
Follow-up
4 weeks
Key result
AAV6-mediated cardiac gene transfer of shRNA against phospholamban reduced PLB mRNA 16-fold but caused severe cardiac toxicity and dysfunction at 4 weeks in healthy canines.
Authors
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AAV6-shRNA PLB knockdown causes cardiac toxicity in canines; leaves open safer vectors for heart failure gene therapy.
Does AAV6-mediated shRNA against PLB safely knock down PLB expression in healthy canines?
While AAV6-mediated shRNA effectively knocks down phospholamban expression in canines, it causes severe cardiac toxicity and dysfunction, suggesting this specific approach may not be a feasible heart failure therapy.
Bish et al. (2011) studied Healthy canines (n=11). AAV6-mediated cardiac gene transfer of shRNA against phospholamban vs. Empty AAV6 capsid or scAAV6 expressing dominant negative PLB was evaluated on PLB expression and cardiac safety. AAV6-mediated cardiac gene transfer of shRNA against phospholamban reduced PLB mRNA 16-fold but caused severe cardiac toxicity and dysfunction at 4 weeks in healthy canines.