Areas covered: Herein, the authors focus on AAV gene therapy for CF, evaluating past experience with this approach and identifying ways forward, based on the progress that has already been made in identifying and overcoming the limitations of AAV gene therapy.
We investigated whether CF sputum acts as a barrier to leading adeno-associated virus (AAV) gene vectors, including AAV2, the only serotype tested in CF clinical trials, and AAV1, a leading candidate for future trials.
A study was conducted to assess health care worker exposure to tgAAVCF during the aerosolized administration of this experimental gene transfer agent in clinical trials for the treatment of cystic fibrosis (CF). tgAAVCF is a recombinant adeno-associated virus (AAV) genetically engineered to contain the human CF transmembrane conductance regulator cDNA.
A prospective, randomized, double-blind, placebo-controlled, within-subjects, phase II clinical trial of the effect AAV-CFTR on clinical recurrence of sinusitis will determine the clinical efficacy of AAV gene therapy for CF.
These studies provide novel insights into AAV gene expression, and this newly described promoter allows for the production of AAV vectors expressing CFTR in those differentiated cells affected in CF.