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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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Self-citationAAV serotype 2 vectors preferentially integrate into active genes in mice
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Physiological Promoters Reduce the Genotoxic Risk of Integrating Gene Vectors
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Self-citationStem cell gene therapy: the risks of insertional mutagenesis and approaches to minimize genotoxicity
Wu, C., & Dunbar, C. E. (2011) · Frontiers of Medicine · doi:10.1007/s11684-011-0159-1 · Cited by 114
Ocular Gene Therapy: A Literature Review with Special Focus on Immune and Inflammatory Responses
Ghoraba, H. H., Akhavanrezayat, A., Karaca, I., Yavari, N., Lajevardi, S., Hwang, J., Regenold, J., Matsumiya, W., Pham, B., Zaidi, M., et al. (2022) · Clinical Ophthalmology · doi:10.2147/opth.s364200 · Cited by 76
Almarza, D., Bussadori, G., Navarro, M., Mavilio, F., Larcher, F., & Murillas, R. (2011) · Gene Therapy · doi:10.1038/gt.2011.12 · Cited by 56
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Finding the needle in the hay stack: Hematopoietic stem cells in Fanconi anemia
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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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