Abstract
Bone marrow hematopoiesis is maintained by hematopoietic stem cells (HSC) (1). Because of their unique features to self-renew and differentiate along all lineages of hematopoietic cells, even a single HSC can completely reconstitute bone marrow hematopoiesis of irradiated recipients (2). Therefore, HSCs are considered to be the ideal target cell population in gene-therapy fields for genetic disorders that are susceptible to bone marrow transplantation (3). However, because most HSCs are quiescent, it is difficult to transduce them using retroviral vectors (4). Furthermore, retroviral vectors, especially Moloney murine leukemia virus (MMLV)-based retroviral vectors that have been commonly used in gene-therapy clinical trials, are very susceptible to de novo methylation in immature cells such as embryonic stem (ES) cells, embryonal carcinoma cells (EC), and HSCs, resulting in shut off/silencing of the transgene expression in vivo (5). This is another obstacle for successful gene delivery into HSCs.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Till, J. E., McCulloch, E. A., and Siminovitch, L. (1964) A stochastic model of stem cell proliferation, based on the growth of spleen colony-forming cell. Proc. Natl. Acad. Sci. USA 51, 29–36.
Osawa, M., Hanada, K., Hamada, H. and Nakauchi H. (1996) Long-term lympho-hematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science 273, 242–245.
Mulligan, R. C. (1993) The basic science of gene therapy. Science 260, 926–932.
Hoogerbrugge, P. M., van Beusechem, V. W., Fischer, A., Debree, M., le Deist, F., Perignon, J. L., et al. (1996) Bone marrow gene transfer in three patients with adenosine deaminase deficiency. Gene Then 3, 179–183.
Wang, L., Robbins, P. B., Carbonaro, D. A., and Kohn, D. B. (1998) High-resolution analysis of cytosine methylation in the 5′ long terminal repeat of retroviral vectors. Hum. Gene Then 9, 2321–2330.
Onodera, M., Nelson, D. M., Yachie, A., Jagadeesh, G. J., Bunnell, B. A., Morgan, R. A., and Blaese, R. M. (1998) Development of improved adenosine deaminase retroviral vectors. J. Virol. 72, 1769–1774.
Halene, S., Wang, L., Cooper, R. M., Bockstoce, D. C, Robbins, P. B., and Kohn, D. B. (1999) Improved expression in hematopoietic and lymphoid cells in mice after transplantation of bone marrow transduced with a modified retroviral vector. Blood 94: 3349–3357.
Tahara-Hanaoka, S., Sudo, K., Ema, H., Miyoshi, H., and Nakauchi, H. (2002) Lentiviral vector-mediated transduction of murine CD34(-) hematopoietic stem cells. Exp. Hematol. 30, 11–17.
Markowitz, D., Goff, S., and Bank, A. (1988) A safe packaging line for gene transfer: separating viral genes on two different plasmids. J. Virol. 62, 1120–1124.
Pear, W S., Nolan, G P., Scott, M. L., and Baltimore, D. (1993) Production of high-titer helper-free retroviruses by transient transfection. Proc. Natl. Acad. Sci. USA 90, 8392–8396.
Miller, A. D. and Buttimore, C. (1986) Redesign of retrovirus packaging cell lines to avoid recombination leading to helper virus production. Mol. Cell Biol. 6, 2895–2902.
Burns, J. C, Friedmann, T., Driever, W., Burrascano, M., and Yee, J. K. (1993) Vesicular stomatitis virus G glycoprotein pseudotyped retroviral vectors: concentration to very high titer and efficient gene transfer into mammalian and nonmam-malian cells. Proc. Natl. Acad. Sci. USA 90, 8759–8760.
Orlic, D., Girard, L. J., Anderson, S. M., Pyle, L. C, Yoder, M. C, Broxmeyer, H. E., and Bodine, D. M. (1998) Identification of human and mouse hematopoietic stem cell populations expressing high levels of mRNA encoding retrovirus receptors. Blood 91, 3247–3254.
Yang, Y, Vanin, E. F., Whitt, M. A., Fornerod, M., Zwart, R., Schneiderman, R. D., and Grosveld, G (1995) Inducible, high-level production of infectious murine leukemia retroviral vector particles pseudotyped with vesicular stomatitis virus G envelope protein. Hum. Gene Ther. 6, 1203–1213.
Dexter, T. M., Allen T., and Lajtha L. G (1997) Conditions controlling the proliferation of haemapoietic stem cells in vitro. J. Cell Physiol. 91, 335–344.
Ogawa, M., Matsuzaki, Y, Nishikawa, S., Hayashi, S., Kunisada, T., Sudo, T., et al. (1991) Expression and function of c-kit in hemopoietic progenitor cells. J. Exp. Med. 174, 63–71.
Miller, A. D., Garcia, J. V., von Suhr, N, Lynch, C. M., Wilson, C, and Eiden, M. V. (1991) Construction and properties of retrovirus packaging cells based on gibbon ape leukemia virus. J. Virol. 65, 2220–2224.
Cosset, F. L., Takeuchi, Y., Battini, J. L., Weiss, R. A., and Collins, M. K. (1995) High-titer packaging cells producing recombinant retroviruses resistant to human serum. J. Virol. 69, 7430–7436.
Sato, T., Laver, J. H., and Ogawa, M. (1999) Reversible expression of CD34 by murine hematopoietic stem cells. Blood 94, 2548–2554.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2004 Humana Press Inc., Totowa, NJ
About this protocol
Cite this protocol
Onodera, M. (2004). Dilivery of Genes to Hematopoietic Stem Cells. In: Heiser, W.C. (eds) Gene Delivery to Mammalian Cells. Methods in Molecular Biology™, vol 246. Humana Press. https://doi.org/10.1385/1-59259-650-9:527
Download citation
DOI: https://doi.org/10.1385/1-59259-650-9:527
Publisher Name: Humana Press
Print ISBN: 978-1-58829-095-3
Online ISBN: 978-1-59259-650-8
eBook Packages: Springer Protocols