Figure 5.

Survival to adulthood was achieved in ASS^−/− pups after prenatal gene delivery, recurrent vector readministration using a different capsid serotype, crossfostering and dietary protein restriction. ASS^−/− pups were injected at E16 and D0 with 2.5 × 10¹¹ vg of rAAV2/rh10-LSP1mASS. All injected pups were then crossfostered to vector-naive dams and received daily doses of L-arginine. The vector was packaged using the serotype 8 capsid and injected into mice at D14 (n = 3) and D28 (n = 3). Uninjected age-matched ASS^+/+ controls were also included (n = 3). Pups were weaned onto a low protein chow (9% wt/wt). (a) The survival curve shows the days on which ASS^−/− pups were culled due to signs of illness. (b) The growth of vector-treated mice was monitored daily over the course of the experiment. (c) Plasma ammonia and (d) liver ASS activity were measured at the time of illness or at the experiment endpoint on D56. Error bars represent SEM, *P < 0.0001 versus ASS^+/+ controls. ASS, argininosuccinate synthetase; vg, vector genome.