Retroviral integration and human gene therapy.
Long-term correction of genetic diseases requires permanent integration of therapeutic genes into chromosomes of affected cells. Retroviral vectors are the most widely used delivery vehicles because of their efficiency and precision of integration. However, retroviral integration can take place at a variety of chromosomal sites, and examples have been reported of integration of therapeutic vectors activating oncogenes and causing cancer in patients. This issue of the JCI presents three articles that update successful human gene therapy trials and furthermore evaluate the sites of integration in cells from treated patients, including samples from individuals experiencing serious adverse events following therapy (see the related articles beginning on pages 2225, 2233, and 2241).
Bushman
Frederic D
FD
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6076, USA. bushman@mail.med.upenn.edu
D018952:Antigens, CD34; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D017988:Gammaretrovirus; D015316:Genetic Therapy; D005822:Genetic Vectors; D015894:Genome, Human; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D038041:Lymphopoiesis / Q000235:genetics*; D016254:Mutagenesis, Insertional; D040641:Quantitative Trait Loci; D013601:T-Lymphocytes; D013997:Time Factors; D016662:Virus Integration / Q000235:genetics*; D053632:X-Linked Combined Immunodeficiency Diseases / Q000235:genetics / Q000628:therapy*
D018952:Antigens, CD34