Lentiviral Gene Therapy For CF

About

The ability to drive high level, sustained transgene expression without eliciting immunogenicity using viral vector based gene transfer agents remains a challenge in the development of safe and effective gene therapy products. The UK Gene Therapy Consortium – a collaboration across Imperial College London, University of Oxford and University of Edinburgh – has developed a novel lentiviral-based gene transfer vector based on pseudotyping SIV with F/HN envelope proteins of Sendai virus. The vectors are designed for optimal respiratory epithelial cell transduction and can be safely administered repeatedly without eliciting an immune response, meeting requirements for treatment of chronic diseases using gene therapy approaches.  We have preclinical proof of concept data for an F/HN SIV lentiviral-based gene therapy for cystic fibrosis. Data shows: (i) direct stable CFTR gene expression in human air liquid interface cultures (ii) efficient transduction of respiratory airway epithelia at clinically relevant levels for cystic fibrosis (iii) sustained expression for lifetime of mouse (c.2 years) from single administration (iv) safe repeat administration to murine airways without loss of efficacy (v) transduction of human lung slices ex vivo  In addition, vector production methods have been developed for optimal production at scale to GMP-compliance. The F/HN SIV lentiviral vector represents an interesting platform with prospects for development of a pipeline of viral gene therapy products targeting the respiratory system.