498. AAV Δ264CFTR Enhances Maturation of ΔF508CFTR and wt CFTR Expression

Abstract

We have presented previously that high dose airway delivery of a pseudotyped AAV2/5 vector to the lungs of Rhesus macaques resulted in enhanced gene transfer and quantitative RNA expression as well as protein expression in non human primates without clinical toxicity. One major limitation to the success of AAV gene therapy for CF is that the large size of the CFTR cDNA insert fills the packaging capacity of AAV viral particles precluding inclusion of a highly efficient promoter. In order to overcome this limitation AAV2/5 pseudotyped vectors were generated expressing a truncated CFTR insert (|[Delta]|264) driven by a chicken beta actin promoter (rAAV-CB-|[Delta]|264-CFTR). We showed previously that this truncated form was capable of reconstituting physiologic function in vitro and in mouse models.