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Murine Leukemia Induced by Retroviral Gene Marking
Abstract
Somatic gene transfer is a promising therapeutic strategy, but it may also evoke new types of side effects related to genetic damage or transgene activity. Retroviral vectors, the best tool current-ly available for stable genetic modification, in-tegrate at random positions in the cellular ge-nome. The risk of mutagenesis of cellular se-quences promoting a malignant phenotype is about 1027 per insertion (1). As tumor develop-ment requires further genetic lesions, a single copy of an otherwise innocuous transgene is not expected to produce severe side effects. Never-theless, we observed leukemia induction in an animal model of retroviral gene marking. Using a replication-defective vector (2), we
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“These severe adverse events are now understood to result from “side effects” of viral integration into the genome.”
From Finding the needle in the hay stack: Hematopoietic stem cells in Fanconi anemia (2009) · cites this paper as [44]
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Research works printed but not linked: 10
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Cited by
Progress and problems with the use of viral vectors for gene therapy
Thomas, C. E., Ehrhardt, A., & Kay, M. A. (2003) · Nature Reviews Genetics · doi:10.1038/nrg1066 · Cited by 2,501
Heckl, D., Kowalczyk, M. S., Yudovich, D., Belizaire, R., Puram, R. V., McConkey, M. E., Thielke, A., Aster, J. C., Regev, A., & Ebert, B. L. (2014) · Nature Biotechnology · doi:10.1038/nbt.2951 · Cited by 555
Effective gene therapy with nonintegrating lentiviral vectors
Yáñez-Muñoz, R. J., Balaggan, K. S., MacNeil, A., Howe, S. J., Schmidt, M., Smith, A. J., Buch, P., MacLaren, R. E., Anderson, P. N., Barker, S. E., et al. (2006) · Nature Medicine · doi:10.1038/nm1365 · Cited by 460
Self-citationAAV serotype 2 vectors preferentially integrate into active genes in mice
Nakai, H., Montini, E., Fuess, S., Storm, T. A., Grompe, M., & Kay, M. A. (2003) · Nature Genetics · doi:10.1038/ng1179 · Cited by 392
Physiological Promoters Reduce the Genotoxic Risk of Integrating Gene Vectors
Zychlinski, D., Schambach, A., Modlich, U., Maetzig, T., Meyer, J., Grassman, E., Mishra, A., & Baum, C. (2008) · Molecular Therapy · doi:10.1038/mt.2008.5 · Cited by 271
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Metadata
- Authors
- Li, Z., Düllmann, J., Schiedlmeier, B., Schmidt, M., von Kalle, C., Meyer, J., Forster, M., Stocking, C., Wahlers, A., Frank, O., Ostertag, W., Kühlcke, K., Eckert, H.-G., Fehse, B., & Baum, C.
- Affiliations
- Heinrich-Pette-Institute, D-20251 Hamburg, Germany.
- University Hospital Eppendorf, D-20249 Hamburg, Germany.
- Albert-Ludwigs-Universität, D-79106 Freiburg, Germany.
- Hannover Medical School, D-30625 Hannover, Germany.
- EUFETS AG, D-55743 Idar-Oberstein, Germany.
- Venue
- Science
- Published
- 2002-04-19
- Volume
- 296
- Issue
- 5567
- Pages
- 497-497
- ISSN
- 0036-8075
- 1095-9203
- Cited by
- 525
- References
- 0
- Language
- en
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- The paper
- Li, Z., Düllmann, J., Schiedlmeier, B., Schmidt, M., von Kalle, C., Meyer, J., Forster, M., Stocking, C., Wahlers, A., Frank, O., Ostertag, W., Kühlcke, K., Eckert, H.-G., Fehse, B., & Baum, C. (2002). Murine Leukemia Induced by Retroviral Gene Marking. Science. https://doi.org/10.1126/science.1068893
