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Cystic Fibrosis Gene Therapy: Improving Lung Gene Transfer Using Lentiviral Vectors

Alton EW.

RDD Europe 2019. Volume 1, 2019: 37-42.

Abstract:

Cystic fibrosis (CF) has been a target for gene therapy since the CFTR gene was cloned 30 years ago. Early expectations of a rapid breakthrough were based on supposed ease of access to the target respiratory epithelium via inhaled aerosols. But the lung is a complex and difficult target organ and gene delivery remains the key limiting factor in the field. Non-viral and viral gene transfer platforms have been explored, and while non-viral gene therapy has been shown to stabilize the decline of lung function in CF patients, the effects were modest. Building on our non-viral gene therapy experience, a new viral vector-based product has been developed. Lentiviral vectors efficiently transduce lung tissue, demonstrate long-lasting effects, and can demonstrate efficacy following three or more repeated transductions. Moving forward, the collaboration between the United Kingdom CF Gene Therapy Consortium, Boehringer Ingelheim, and Oxford BioMedica enables focused and coordinated efforts assessing lentiviral vector safety and production scale-up, which will be required to move this vector into clinical lung gene therapy studies.