Safety of vector administration was determined by measurements of pulmonary mechanics, arterial blood gas analysis, chest radiographs, and bronchoalveolar lavage (BAL) fluid analysis including cell count and quantification of inflammatory cytokines.
Furthermore, the risks of detrimental effects related to systemic vector administration are avoided.
It is important to consider this question in the context of the fact that the two participants who received the high dose of vector (2 × 10 vector genomes per kg) had transient, asymptomatic elevation of serum aminotransferase levels, which although milder in extent and later following vector administration, were similar to what had occurred in the previous liver-directed AAV trial.
They also address the need for strategies to carefully dose-titrate AAV vectors to avoid overexpression7, or to target systemic diseases35 in which multiple vector administrations are likely needed to achieve full therapeutic efficacy36.
Seven days after vector administration, RNA was isolated from the livers and 30 μg) or 60 μg) was analyzed by northern blot hybridization.
Although liver enzyme elevation is not typically observed in animal models of AAV-mediated gene therapy17,43, we did observe evidence of CD8 T cell infiltrates in the liver after vector administration, which were inhibited by SVP[Rapa] treatment (Fig. 4a).
Before vector administration, rats were anesthetized with ketamine (72 mg/kg) and xylazine (64 mg/kg) by intraperitoneal injection.
To optimize the time point of vector administration, mice were injected with DC-LV-OVA at the rear footpad 3, 7, 10, or 14 days postinjection with hydrogels.
The administration is lethargic".
All the patients except those who received the interleukin-2 gene in a vaccine vector (via an intratumoral administration) were treated with an intrapleural injection of Ad.
