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 vecto
r 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 a
ctively dividing in order for transduction and therefore gene delivery to o
ccur. This limitation precludes the use of MLV for delivering genes to the
adult CNS, where very little cell division is occurring. However, we specul
ated that this inherent limitation of MLV 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 ind
uce cell division, could enhance MLV-based gene transfer to the adult brain
. We now show that an exogenous application of basic fibroblast growth fact
or induces cell division in vivo. Under these conditions, where cells of th
e adult brain are stimulated to divide, MLV-based gene transfer is signific
antly enhanced. This novel approach precludes any vector modifications and
provides a simple and effective way of delivering genes to cells of the adu
lt brain utilizing MLV-based retroviral vectors.