Optimization of equine infectious anemia derived vectors for hematopoietic cell lineage gene transfer

J. P. O'Rourke, J. C. Olsen, B. A. Bunnell

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Gene transfer into hematopoietic cells may allow correction of a variety of hematopoietic and metabolic disorders. Optimized HIV-1 based lentiviral vectors have been developed for improved gene transfer and transgene expression into hematopoietic cells. However, the use of HIV-1 based vectors for human gene therapy may be limited due to ethical and biosafety issues. We report that vectors based on the non-primate equine infectious anemia virus (EIAV) transduce a variety of human hematopoietic cell lines and primary blood cells. To investigate optimization of gene expression in hematopoietic cells, we compared a variety of post-transcriptional elements and promoters in the context of EIAV vectors. We observed cell specific increase in the number of transgene expressing cells with the different post-transcriptional elements, whereas the use of elongation factor alpha 1 (EFα1) promoter resulted in significant increases in both the number of transgene expressing cells and the level of transgene protein in all cell types tested. We then demonstrate increased transduction of hematopoietic cells using a second-generation EIAV vector containing a self-inactivating EIAV LTR and the EIAV central polypurine tract (cppt). These data suggest that optimized EIAV vectors may be a suitable alternative to HIV-1 vectors for use in hematopoietic gene therapy.

Original languageEnglish
Pages (from-to)22-29
Number of pages8
JournalGene Therapy
Volume12
Issue number1
DOIs
StatePublished - Jan 2005

Keywords

  • EIAV
  • Hematopoietic
  • Lentivirus

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