IFN-beta gene transfer into the central nervous system using bone marrow cells as a delivery system.

Abstract

The peripheral delivery of interferon-beta (IFN-beta) for the treatment of central nervous system (CNS) diseases is only partially effective because of the blood-brain barrier (BBB). To circumvent this problem, we evaluated the feasibility of genetically altering bone marrow cells ex vivo and using them as vehicles to transfer the IFN-beta cDNA into the mouse CNS. An IFN-beta retroviral expression vector (pLXSN-IFNbeta) was used to stably transfect PA317 cells. The supernatant from these producer cells, which expressed IFN-beta mRNA and protein, were used to infect bone marrow cells. When transplanted into irradiated mice, IFN-beta-engineered marrow cells accessed the CNS and expressed IFN-beta mRNA and protein. Marrow cells transduced with a control neomycin vector entered the brain and expressed the neomycin but not the IFN-beta gene. In the CNS, IFN-beta delivered by marrow cells induced the mRNA expression of 2',5'-oligoadenylate synthetase (2',5'-OAS), indicating biologic activity. Our findings demonstrating that bone marrow cells can serve as a delivery system for IFN-beta cDNA into the CNS could have implications for the treatment of neurologic disorders, such as multiple sclerosis (MS), viral encephalitis, and brain tumors.

Cite this paper

@article{Makar2002IFNbetaGT, title={IFN-beta gene transfer into the central nervous system using bone marrow cells as a delivery system.}, author={Tapas Kumar Makar and Susan Wilt and Zhongyun Dong and Paul Fishman and M Maral Mouradian and Suhayl Dhib-Jalbut}, journal={Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research}, year={2002}, volume={22 7}, pages={783-91} }