FIG. 1.

Proteasome inhibitors dramatically induce rAAV2/1 transduction of the ferret lung. (A) Fourteen-day-old ferrets were infected with 5×10¹⁰ DRP of rAAV2/1.CBA-RL in 600 μl inoculum containing the indicated concentrations of Dox through intratracheal instillation. Graph shows the mean±SEM of luciferase activity (RLU/mg protein) measured at 8 days postinfection (n=4 animals for each condition). (B–D) Five-day-old ferrets were infected with 2.5×10¹¹ DRP of rAAV2/1.RSV-AP in the presence or absence of 250 μM Dox (21.6 μg in 150 μl inoculum). (E) Twelve-day-old ferrets were infected with 1×10¹² DRP of rAAV2/1.RSV-AP in the presence of 250 μM Dox (72 μg in 500 μl inoculum); this embedded lung sample was not inflated. (F) Eighteen-day-old ferrets were infected with 1×10¹² DRP of rAAV2/1.RSV-AP in the presence of 250 μM Dox (86.4 μg in 600 μl inoculum). Dark purple staining demonstrates the expression of the alkaline phosphatase reporter at 8 days postinfection. Images in (C–F) were acquired at the 100× magnification. Dox, doxorubicin; DRP, DNase-resistant particles; rAAV, recombinant adeno-associated virus; SEM, standard error of the mean. Color images available online at www.liebertpub.com/hum