A roadmap to safe, efficient, and stable lentivirus-mediated gene therapy with hematopoietic cell transplantation.
Hematopoietic stem cells comprise a prominent target for gene therapy aimed at treating various genetic and acquired disorders. A number of limitations associated with hematopoietic cell transplantation can be circumvented by the use of cells stably modified by retroviral gene transfer. Oncoretroviral and lentiviral vectors offer means for generating efficient and stable transgene expression. This review summarizes the state of the field today in terms of vector development and clinical experimentation. In particular, concerns with the safety of retroviral vectors intended for clinical gene transfer, applicability of preclinical data in directing clinical trial design, and recent research aimed at resolving some of these issues are addressed. Finally, this review underlines the specific advantages offered by lentiviral gene-transfer vectors for gene therapy in stem cells.
Neschadim
Anton
A
Division of Stem Cell and Developmental Biology, Ontario Cancer Institute, Toronto, Ontario, Canada.
McCart
J Andrea
JA
Keating
Armand
A
Medin
Jeffrey A
JA
D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000009:adverse effects / Q000096:biosynthesis / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D011994:Recombinant Proteins; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000628:therapy; D052416:Targeted Gene Repair / Q000379:methods; D014182:Transplantation, Autologous
D011994:Recombinant Proteins