Current Status and Future Directions of Gene and Cell Therapy for Cystic Fibrosis

Although the development of gene therapy for cystic fibrosis (CF) was high priority for many groups in academia and industry in the first 10–15 years after cloning the cystic fibrosis transmembrane conductance regulator (CFTR) gene, more recently active research into CF gene therapy is only being performed by a small number of committed groups. However, despite the waning enthusiasm, which is largely due to the realization that gene transfer into lungs is more difficult than originally thought, and the fact that meaningful clinical trials are expensive and difficult to perform, gene therapy continues to hold promise for the treatment of CF lung disease. Problems related to repeat administration of adenovirus and adeno-associated virus-based vectors led to a focus on non-viral vectors in clinical trials. However, the recent evidence that lentiviral vectors may be able to evade the immune system and, thereby, allow for repeat administration and long-lasting expression opens new doors for the use of viral vectors in the context of CF gene therapy. In addition, early pre-clinical studies have recently been initiated to address cell therapy-based approaches for CF. In this review, we discuss recent developments with viral and non-viral vectors and cell therapy, and provide an update on clinical gene therapy studies.