Retroviral approaches to gene therapy of cystic fibrosis.
Retroviral vectors are attractive as vectors for gene therapy of cystic fibrosis because of their ability to integrate into the host cell genome, which may lead to long-term expression and, perhaps, a cure. Nevertheless, retroviral applications for gene transfer to airway epithelia have been limited by low titers and a requirement for proliferating cells. Significant advances in pseudotyping of retroviruses and in retroviral production have reduced some of the concerns regarding titer. The development of lentiviral vectors that transduce nondividing cells has also helped to establish that retroviral approaches for gene therapy of cystic fibrosis are feasible. However, the apical membrane of the airway epithelium remains a formidable barrier to gene transfer. In this review, I will discuss limitations of current retroviral gene transfer vectors and strategies to improve retroviral gene transfer efficiency to airway epithelia in vivo.
Johnson
L G
LG
Cystic Fibrosis Pulmonary Research and Treatment Center, Department of Medicine, The University of North Carolina at Chapel Hill, 27599, USA. Larry_Johnson@med.unc.edu
D000818:Animals; D003550:Cystic Fibrosis / Q000517:prevention & control / Q000628:therapy*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D012190:Retroviridae / Q000145:classification / Q000235:genetics*
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator