December 10, 2002Human Gene Therapy
Preexisting Antiadenoviral Immunity and Regional Myocardial Gene Transfer: Modulation by Nitric Oxide
Key result
Intracardiac NOS3 gene transfer in immunized pigs resulted in 200-fold greater median reporter transgene expression in the subendocardium compared to control virus coinfusion (P=0.02).
Why the study?
Does NOS3 gene transfer improve adenoviral-mediated myocardial gene expression and reduce inflammation in pigs with preexisting antiadenoviral immunity?
Population
Naive pigs and pigs immunized by intravenous injection of control virus AdRR5.
Comparison
Infusion of adenoviral vectors expressing human… vs Infusion of AdLuc alone, or coinfusion of AdLuc…
Design
Preclinical
Follow-up
3 days
Authors
Discussion
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Implication
Supports testing NOS3 co-delivery to boost gene therapy in immunized hosts; hypothesis-generating for human translation.
Structured PICO
Does NOS3 gene transfer improve adenoviral-mediated myocardial gene expression and reduce inflammation in pigs with preexisting antiadenoviral immunity?
P
Population
Naive and immunized pigs evaluated for the effect of preexisting antiadenoviral immunity on intracardiac gene transfer and its modulation by nitric oxide.
I
Intervention
Infusion of adenoviral vectors expressing human nitric oxide synthase 3 (AdNOS3) alone or coinfused with firefly luciferase (AdLuc) into the great cardiac vein.
C
Comparator
Infusion of AdLuc alone, or coinfusion of AdLuc and control virus AdRR5, in naive or immunized pigs.
O
Outcome
Myocardial transgene expression (luciferase and NOS3 transcript levels), mononuclear cell infiltration, and myocyte apoptosis at 3 days.surrogate
Main Result
Effect estimate: 200-fold greater
Absolute Event Rate: 1000% vs 45%
p-value: p=0.02
Intracardiac NOS3 gene transfer can overcome the barrier of preexisting antiadenoviral immunity, improving myocardial gene expression and reducing inflammation and apoptosis in a porcine model.
Cite This Study
Szelid et al. (2002) studied Preexisting antiadenoviral immunity. AdNOS3 gene transfer vs. AdLuc and AdRR5 co-infection was evaluated on Median reporter transgene expression levels in the subendocardium (200-fold greater, p=0.02). Intracardiac NOS3 gene transfer in immunized pigs resulted in 200-fold greater median reporter transgene expression in the subendocardium compared to control virus coinfusion (P=0.02).