IFN-βGene Transfer into the Central Nervous System Using Bone Marrow Cells as a Delivery System

Publisher Website
Google Scholar
Abstract
The peripheral delivery of interferon-β (IFN-β) 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-β cDNA into the mouse CNS. An IFN-β retroviral expression vector (pLXSN-IFNβ) was used to stably transfect PA317 cells. The supernatant from these producer cells, which expressed IFN-β mRNA and protein, were used to infect bone marrow cells. When transplanted into irradiated mice, IFN-β-engineered marrow cells accessed the CNS and expressed IFN-β mRNA and protein. Marrow cells transduced with a control neomycin vector entered the brain and expressed the neomycin but not the IFN-β gene. In the CNS, IFN-β 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-β cDNA into the CNS could have implications for the treatment of neurologic disorders, such as multiple sclerosis (MS), viral encephalitis, and brain tumors.