Retrovirus-mediated gene transfer into human hematopoietic stem cells

Peter Chu, Carolyn Lutzko, Alexander Keith Stewart, Ian D. Dubé

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Human hematopoietic stem cells genetically modified by retroviral-mediated gene transfer may offer new treatment options for patients with genetic disease. The potential of gene-modified hematopoietic stem cells as vehicles for gene delivery was first illustrated by the demonstration that hematopoietic systems of lethally irradiated mice can be reconstituted with retroviral vector transduced syngeneic bone marrow, and that these cells can in turn provide genetically marked progeny which persist in blood and marrow over extended time periods. In contrast, hematopoietic stem cells from large animals prove difficult to transduce with retroviral vectors and are consequently less likely to function as vehicles for long-term gene therapy. Indeed, clinically relevant levels of gene transfer into large animal and human hematopoietic stem cells has not been widely achieved. The need for improved retroviral vector systems and for understanding the biology of hematopoietic stem cell gene transfer continue to fuel intense research activity. Preliminary results from human stem cell gene marking and gene therapy trials currently underway are encouraging. This contribution reviews the underlying concepts relevant to retroviral-mediated gene transfer into hematopoietic stem cells. We survey the evolution of approaches for gene transfer into hematopoietic stem cells, from murine and large animal models to the first human clinical trials. Finally, we discuss new strategies which are currently being pursued.

Original languageEnglish (US)
Pages (from-to)184-192
Number of pages9
JournalJournal of Molecular Medicine
Volume76
Issue number3-4
DOIs
StatePublished - 1998
Externally publishedYes

Fingerprint

Retroviridae
Hematopoietic Stem Cells
Genes
Genetic Therapy
Hematopoietic System
Inborn Genetic Diseases
Systems Biology
Bone Marrow Cells
Stem Cells
Animal Models
Bone Marrow
Clinical Trials
Research

Keywords

  • Gene therapy
  • Gene transfer
  • Hematopoietic stem cells

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Retrovirus-mediated gene transfer into human hematopoietic stem cells. / Chu, Peter; Lutzko, Carolyn; Stewart, Alexander Keith; Dubé, Ian D.

In: Journal of Molecular Medicine, Vol. 76, No. 3-4, 1998, p. 184-192.

Research output: Contribution to journalArticle

Chu, Peter ; Lutzko, Carolyn ; Stewart, Alexander Keith ; Dubé, Ian D. / Retrovirus-mediated gene transfer into human hematopoietic stem cells. In: Journal of Molecular Medicine. 1998 ; Vol. 76, No. 3-4. pp. 184-192.
@article{b5ad2371038d487c9837fe63ae986da1,
title = "Retrovirus-mediated gene transfer into human hematopoietic stem cells",
abstract = "Human hematopoietic stem cells genetically modified by retroviral-mediated gene transfer may offer new treatment options for patients with genetic disease. The potential of gene-modified hematopoietic stem cells as vehicles for gene delivery was first illustrated by the demonstration that hematopoietic systems of lethally irradiated mice can be reconstituted with retroviral vector transduced syngeneic bone marrow, and that these cells can in turn provide genetically marked progeny which persist in blood and marrow over extended time periods. In contrast, hematopoietic stem cells from large animals prove difficult to transduce with retroviral vectors and are consequently less likely to function as vehicles for long-term gene therapy. Indeed, clinically relevant levels of gene transfer into large animal and human hematopoietic stem cells has not been widely achieved. The need for improved retroviral vector systems and for understanding the biology of hematopoietic stem cell gene transfer continue to fuel intense research activity. Preliminary results from human stem cell gene marking and gene therapy trials currently underway are encouraging. This contribution reviews the underlying concepts relevant to retroviral-mediated gene transfer into hematopoietic stem cells. We survey the evolution of approaches for gene transfer into hematopoietic stem cells, from murine and large animal models to the first human clinical trials. Finally, we discuss new strategies which are currently being pursued.",
keywords = "Gene therapy, Gene transfer, Hematopoietic stem cells",
author = "Peter Chu and Carolyn Lutzko and Stewart, {Alexander Keith} and Dub{\'e}, {Ian D.}",
year = "1998",
doi = "10.1007/s001090050207",
language = "English (US)",
volume = "76",
pages = "184--192",
journal = "Journal of molecular medicine (Berlin, Germany)",
issn = "0946-2716",
publisher = "Springer Verlag",
number = "3-4",

}

TY - JOUR

T1 - Retrovirus-mediated gene transfer into human hematopoietic stem cells

AU - Chu, Peter

AU - Lutzko, Carolyn

AU - Stewart, Alexander Keith

AU - Dubé, Ian D.

PY - 1998

Y1 - 1998

N2 - Human hematopoietic stem cells genetically modified by retroviral-mediated gene transfer may offer new treatment options for patients with genetic disease. The potential of gene-modified hematopoietic stem cells as vehicles for gene delivery was first illustrated by the demonstration that hematopoietic systems of lethally irradiated mice can be reconstituted with retroviral vector transduced syngeneic bone marrow, and that these cells can in turn provide genetically marked progeny which persist in blood and marrow over extended time periods. In contrast, hematopoietic stem cells from large animals prove difficult to transduce with retroviral vectors and are consequently less likely to function as vehicles for long-term gene therapy. Indeed, clinically relevant levels of gene transfer into large animal and human hematopoietic stem cells has not been widely achieved. The need for improved retroviral vector systems and for understanding the biology of hematopoietic stem cell gene transfer continue to fuel intense research activity. Preliminary results from human stem cell gene marking and gene therapy trials currently underway are encouraging. This contribution reviews the underlying concepts relevant to retroviral-mediated gene transfer into hematopoietic stem cells. We survey the evolution of approaches for gene transfer into hematopoietic stem cells, from murine and large animal models to the first human clinical trials. Finally, we discuss new strategies which are currently being pursued.

AB - Human hematopoietic stem cells genetically modified by retroviral-mediated gene transfer may offer new treatment options for patients with genetic disease. The potential of gene-modified hematopoietic stem cells as vehicles for gene delivery was first illustrated by the demonstration that hematopoietic systems of lethally irradiated mice can be reconstituted with retroviral vector transduced syngeneic bone marrow, and that these cells can in turn provide genetically marked progeny which persist in blood and marrow over extended time periods. In contrast, hematopoietic stem cells from large animals prove difficult to transduce with retroviral vectors and are consequently less likely to function as vehicles for long-term gene therapy. Indeed, clinically relevant levels of gene transfer into large animal and human hematopoietic stem cells has not been widely achieved. The need for improved retroviral vector systems and for understanding the biology of hematopoietic stem cell gene transfer continue to fuel intense research activity. Preliminary results from human stem cell gene marking and gene therapy trials currently underway are encouraging. This contribution reviews the underlying concepts relevant to retroviral-mediated gene transfer into hematopoietic stem cells. We survey the evolution of approaches for gene transfer into hematopoietic stem cells, from murine and large animal models to the first human clinical trials. Finally, we discuss new strategies which are currently being pursued.

KW - Gene therapy

KW - Gene transfer

KW - Hematopoietic stem cells

UR - http://www.scopus.com/inward/record.url?scp=0031935433&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031935433&partnerID=8YFLogxK

U2 - 10.1007/s001090050207

DO - 10.1007/s001090050207

M3 - Article

C2 - 9535551

AN - SCOPUS:0031935433

VL - 76

SP - 184

EP - 192

JO - Journal of molecular medicine (Berlin, Germany)

JF - Journal of molecular medicine (Berlin, Germany)

SN - 0946-2716

IS - 3-4

ER -