Pre-existing herpes simplex virus 1 (HSV-1) immunity decreases, but does not abolish, gene transfer to experimental brain tumors by a HSV-1 vector.

The influence of pre-existing anti-herpes simplex type 1 (HSV-1) immunity on HSV-1 vector-mediated gene transfer to glioma cells was analyzed in this gene marking study using intracranial D74 gliomas in syngeneic Fischer rats. The HSV-1 mutant virus used, hrR3, is defective in ribonucleotide reductase and bears the marker genes E. coli lacZ and HSV-1 thymidine kinase (HSVtk).

Long-term expression of the gene encoding green fluorescent protein in murine hematopoietic cells using retroviral gene transfer.

Background: A major goal in retroviral-based gene therapy is to establish methods that allow for selection and tracking of transduced cell populations. Green fluorescent protein (GFP) may be useful for gene therapy applications because it is a naturally fluorescent protein that can be detected using conventional flow cytometers facilitating rapid analysis and purification of transduced cell populations. However, it is unknown whether GFP can be stably expressed in vivo, particularly in multiple bone marrow-derived cell lineages.

Green fluorescent protein as a reporter for retrovirus and helper virus-free HSV-1 amplicon vector-mediated gene transfer into neural cells in culture and in vivo.

Green fluorescent protein (GFP) is an effective marker for retrovirus and herpes virus vector-mediated gene transfer into various central nervous system-derived cells, both proliferative and non-proliferative, in culture and in vivo. Retrovirus vectors were used to stably transduce several rat and human glioma lines, and a multipotent mouse neural progenitor line in culture. Implantation of selected pools of transduced glioma cells into rodent brain allowed clear visualization of the tumor and the invading tumor edge.

Retrovirus-mediated gene therapy of experimental brain neoplasms using the herpes simplex virus-thymidine kinase/ganciclovir paradigm.

Recent results in experimental brain tumors indicate that transfer of sensitizing genes to tumor cells in vivo with subsequent drug treatment can reduce tumor masses and prolong the survival of rodents. In the present study, the 9L rat gliosarcoma model was used to evaluate the therapeutic effectiveness of the herpes simplex virus-thymidine kinase (HSV-tk) gene, delivered by a retrovirus vector, against tumor cells in the rat brain after systemic application of the nucleoside analogue ganciclovir (GCV). The HSV-tk gene was inserted into a retroviral vector (pMFG), which was produced using the amphotropic packaging cell line CRIP-MFG-S-HSV-TK.

Disruption of circadian regulation by brain grafts that overexpress Alzheimer beta/A4 amyloid.

Alzheimer disease patients exhibit irregularities in the patterns of normally circadian (daily) rhythms. Alzheimer-type pathology has been reported in the hypothalamus and in the suprachiasmatic nuclei, the putative site of the circadian oscillator. We examined the relationship between the neuropathology of Alzheimer disease, as modeled by an animal system, and circadian dysregulation by grafting genetically transformed cells that overexpress beta/A4 amyloid into the suprachiasmatic nuclei of adult rats.