Human Gene Therapy
Hum Gene Ther. 2015 May;26(5):266-75.
The cystic fibrosis transmembrane conductance regulator (CFTR) gene was identified in 1989. This opened the door for development of CF gene therapy which has been actively pursued for the last 20 years.
Although 26 clinical trials involving approximately 450 patients have been carried out, the vast majority of these trials were short and included small numbers of patients and not designed to assess clinical benefit, but to establish safety and proof-of-concept for gene transfer using molecular endpoints such as the detection of recombinant mRNA or correction of the ion transport defect.
The only currently published trial designed and powered to assess clinical efficacy (defined as improvement in lung function) administered AAV2-CFTR to the lungs of CF patients (Moss et al 2007). The UK CF Gene Therapy Consortium has recently (Autumn 2014) completed the first non-viral gene therapy trial designed to answer whether repeated non-viral gene transfer (12 doses over 12 months) can lead to clinical benefit.
The demonstration that the molecular defect in CFTR can be corrected using small molecule drugs and the success of gene therapy in other monogenic diseases, is boosting interest in CF gene therapy. Recent developments are discussed here.