PROSPECTS FOR VIRUS-BASED GENE-THERAPY FOR CYSTIC-FIBROSIS

Gene therapy for cystic fibrosis (CF) could potentially be accomplished with one of several recombinant virus vectors, including a murine retrovirus (MMuLV), adenovirus, or adeno-associated virus (AAV). All these vectors take advantage of their respective viruses' mechanisms for delivery of viral DNA to cells, evasion of lyosomal degradation, and optimization of the levels and duration of expression of viral (or vector) DNA. Each has its own unique life cycle, however. The differences among these viruses result in certain advantages and disadvantages, such as the requirement of retroviruses for active cell division, and the potential pathogenic effects from expression of certain adenovirus genes present in adenovectors. While no single vector may be optimal for CF gene therapy in humans, new techniques, such as receptor-mediated gene transfer, seek to take advantage of the desirable properties of one or more of the virus-based systems while avoiding certain potential hazards.