Targeted gene therapy to antigen-presenting cells in the central nervous system using hematopoietic stem cells

Maciej S. Lesniak, Erin Kelleher, Drew Pardoll, Yan Cui

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Background: Hematopoietic stem cells (HSC) have been previously used as vectors for gene therapy of systemic disease. The effectiveness of HSC-mediated gene therapy largely depends on efficient gene delivery into long-term repopulating progenitors and targeted transgene expression in an appropriate progeny of the transduced pluripotent HSCs. In the present study, we examined the feasibility of using HSC transduced with self-inactivating (SIN) lentiviral vectors for the delivery of gene therapy to the central nervous system (CNS). Material and methods: We constructed two SIN lentiviral vectors, EF.GFP and DR.GFP, to express the green fluorescent protein (GFP) gene controlled solely by the promoter of either a housekeeping gene EF-1α or the human HLA-DRα gene, which is selectively expressed in antigen-presenting cells. Results: We demonstrated that both vectors efficiently transduced human pluripotent CD34+ cells capable of engrafting NOD/SCID mice. Only the DR.GFP vector mediated transgene expression in the murine CNS containing human HLA-DR+ cells. These cells express surface markers characteristic of resident CNS microglia. Furthermore, human dendritic cells derived from transduced and engrafted human cells potently stimulated allogeneic T cell proliferation. Conclusions: The present study demonstrated successful targeting of transgene expression to CNS microglia after stable gene transduction of pluripotent HSC.

Original languageEnglish (US)
Pages (from-to)820-826
Number of pages7
JournalNeurological research
Issue number8
StatePublished - Dec 1 2005


  • Central nervous system
  • Gene therapy
  • Hematopoietic stem cells
  • Microglia

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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