A gene therapy for cystic fibrosis (CF) lung disease by intralumenal
delivery of therapeutic transgenes into the lung is a logical treatment
strategy if efficient gene transfer can be achieved without
detrimental effects to the patient. Indeed, pioneering work in the
late 1980s showed that genetically engineered viruses could deliver
the CF corrective transgene to cultured cells from patients with CF.
However, after many attempts to deliver the corrective gene to the
lungs of patients with CF in vivo and with the luxury of 20/20 hindsight,
it is realized that although logical, the strategy to accomplish
this task did not appreciate the evolution of the lung to resist invasion
by pathogens such as viruses. It is now apparent that several levels
of barriers exist that restrict exogenous gene delivery to the airway
epithelium by commonly used viral vectors. Components of the
innate and cell-mediated immune system collectively limit both
the access to and duration of gene transfer vectors to the airway
epithelium.Alternative viral vectors that have evolved to circumvent
these barriers will require further development if gene transfer is
ever to be considered a therapy for CF lung disease
