Growth factor enhanced retroviral gene transfer to the adult central nervous system.
The use of viral vectors for gene delivery into mammalian cells provides a new approach in the treatment of many human diseases. The first viral vector approved for human clinical trials was murine leukemia virus (MLV), which remains the most commonly used vector in clinical trials to date. However, the application of MLV vectors is limited since MLV requires cells to be actively dividing in order for transduction and therefore gene delivery to occur. This limitation precludes the use of MLV for delivering genes to the adult CNS, where very little cell division is occurring. However, we speculated that this inherent limitation of ML V may be overcome by utilizing the known mitogenic effect of growth factors on cells of the CNS. Specifically, an in vivo application of growth factor to the adult brain, if able to induce cell division, could enhance MLV-based gene transfer to the adult brain. We now show that an exogenous application of basic fibroblast growth factor induces cell division in vivo. Under these conditions, where cells of the adult brain are stimulated to divide, MLV-based gene transfer is significantly enhanced. This novel approach precludes any vector modifications and provides a simple and effective way of delivering genes to cells of the adult brain utilizing MLV-based retroviral vectors.
Department of Anatomy, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0709, USA.
L A
LA
King
K A
KA
Mitrophanous
L A
LA
Clark
V N
VN
Kim
J B
JB
Rohll
A J
AJ
Kingsman
R J
RJ
Colello
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001345:Autoradiography; D002455:Cell Division; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use*; D005822:Genetic Vectors / Q000008:administration & dosage*; D007150:Immunohistochemistry; D007763:Lac Operon; D009052:Leukemia Virus, Murine / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage
D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2