Stem cell-derived erythroid cells mediate long-term systemic protein delivery Journal Article


Authors: Chang, A. H.; Stephan, M. T.; Sadelain, M.
Article Title: Stem cell-derived erythroid cells mediate long-term systemic protein delivery
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. © 2006 Nature Publishing Group.
Keywords: controlled study; protein expression; human cell; nonhuman; proteins; mouse; phenotype; animals; mice; cells, cultured; erythropoiesis; animal experiment; animal model; in vivo study; oncology; biotechnology; mice, inbred c57bl; risk assessment; carcinogenesis; stem cell; immunological tolerance; immunology; recombinant proteins; lentivirus vector; erythroid cell; hematopoietic stem cells; stem cells; immunomodulation; hematopoietic stem cell; gene silencing; ex vivo study; hemophilia b; erythroid cells; factor ix; protein arginine methyltransferase; cells; protein engineering; cell based gene therapy; human factor ix (hfix); transcriptional silencing; bleeding disorder; genetic enhancement
Journal Title: Nature Biotechnology
Volume: 24
Issue: 8
ISSN: 1087-0156
Publisher: Nature Publishing Group  
Date Published: 2006-08-01
Start Page: 1017
End Page: 1021
Language: English
DOI: 10.1038/nbt1227
PUBMED: 16845377
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 39" - "Export Date: 4 June 2012" - "CODEN: NABIF" - "Source: Scopus"
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MSK Authors
  1. Alex Hongsheng Chang
    9 Chang
  2. Michel W J Sadelain
    492 Sadelain