Gene therapy for pulmonary diseases.
The common fatal hereditary disorders, alpha 1-antitrypsin (alpha 1AT) deficiency and cystic fibrosis (CF), are clinical models for the common lung diseases, emphysema and chronic bronchitis, respectively. Both are potentially amenable to therapeutic intervention by gene therapy, in which the relevant gene is used to modify cells of the affected individual. Although the gene therapy strategies for these diseases are conceptually quite different, a promising approach for both is the in vivo administration of a recombinant replication deficient adenovirus vector containing a normal copy of the abnormal gene. If the goal is to express the normal extracellular anti-protease alpha 1 AT, the route of administration could be directly into the lung, liver or vascular endothelium. If the goal is to express the normal transmembrane protein defective in CF epithelial cells, the new gene will need to be delivered directly to the affected cells. The feasibility of these approaches has been demonstrated in vitro and in vivo in experimental animals.
Rosenfeld
M A
MA
Pulmonary Branch, National Heart, Lung, and Blood Institute National Institutes of Health, Bethesda, Maryland 20892.
Ronald
G
G
Crystal
R G
RG
D000256:Adenoviridae / Q000235:genetics; D003550:Cystic Fibrosis / Q000235:genetics / Q000628:therapy*; D003677:Deficiency Diseases / Q000235:genetics / Q000628:therapy*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D011995:Recombination, Genetic; D012190:Retroviridae / Q000235:genetics; D019896:alpha 1-Antitrypsin Deficiency