Toward Gene Therapy for Cystic Fibrosis Using a Lentivirus Pseudotyped With Sendai Virus Envelopes

摘要: Gene therapy for cystic fibrosis (CF) is making encouraging progress into clinical trials. However, further improvements in transduction efficiency are desired. To develop a novel gene transfer vector that improved and truly effective CF therapy, simian immunodeficiency virus (SIV) was pseudotyped with envelope proteins from Sendai (SeV), which known to efficiently transduce unconditioned airway epithelial cells the apical side. This evaluated mice vivo vitro directed toward therapy. Here, we show (i) can produce relevant titers of an SIV SeV use, (ii) this respiratory epithelium murine nose at levels may be benefit CF, (iii) achieved single formulation, without need preconditioning, (iv) expression last 15 months, (v) readministration feasible, (vi) human air–liquid interface (ALI) cultures, (vii) functional transmembrane conductance regulator (CFTR) chloride channels generated vitro. Our data suggest lentiviral provide step change programme CF.