Stem cell-derived erythroid cells mediate long-term systemic protein delivery. Academic Article uri icon

Overview

abstract

  • We demonstrate here the capacity of erythroid cells to mediate long-term, systemic and therapeutic protein delivery in vivo. By targeting human factor IX (hFIX) expression to late-stage erythropoiesis, we achieve long-term hFIX secretion at levels significantly higher (>tenfold) than those obtained with an archetypal ubiquitous promoter in a mouse model of hemophilia B. Erythroid cell-derived hFIX is biologically active, resulting in phenotypic correction of the bleeding disorder. In addition to achieving high expression levels and resistance to transcriptional silencing, red cell-mediated protein delivery offers multiple advantages including immune tolerance induction, reduction of the risk of insertional oncogenesis and relative ease of application by either engrafting transduced hematopoietic stem cells or transfusing ex vivo-generated, stem cell-derived erythroid cells.

publication date

  • July 16, 2006

Research

keywords

  • Erythroid Cells
  • Factor IX
  • Hematopoietic Stem Cells
  • Protein Engineering
  • Recombinant Proteins

Identity

Scopus Document Identifier

  • 33747076039

Digital Object Identifier (DOI)

  • 10.1038/nbt1227

PubMed ID

  • 16845377

Additional Document Info

volume

  • 24

issue

  • 8