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

Tapas Kumar Makar, Susan Wilt, Zhongyun Dong, Paul Fishman, M. Maral Mouradian, Suhayl Dhib-Jalbut

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)783-791
Number of pages9
JournalJournal of Interferon and Cytokine Research
Volume22
Issue number7
DOIs
StatePublished - 2002

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cell Biology
  • Virology

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