Retroviral Transfer and Expression of Drug Resistance Genes in Hematopoietic Cells
Genes conferring resistance to anticancer drugs are expressed in hematopoietic cells to increase the therapeutic index of chemotherapy and to establish a system for dominant selection of gene-modified cells in vivo. We have developed powerful retroviral vectors for this approach. These vectors are known as Friend mink cell focus-forming/murine embryonic stem cells virus hybrid vectors (FMEV), characterised by mediating high constitutive transgene expression in hematopoietic cells. In our recent work, we have elaborated a new generation of FMEV expressing dominant selection markers like multidrug resistance 1 (MDR1) alone or in combination with other genes at further increased efficiency and safety.
KeywordsToxicity Leukemia Recombination Aldehyde Sarcoma
Unable to display preview. Download preview PDF.
- 7.Stocking C, Baum C (1997) Gene transfer into haematopoietic cells. In: :“Bailliere’s Clinical Haematology, Vol. 10: Molecular Haemopoiesis”, ed. by Whetton AD, Bailliere Tindall London, pp. 445–466Google Scholar
- 8.Baum C, Stocking C, Wagener T, Eckert H-G, Ostertag W (1997) Gene transfer and transgene expression in hematopoietic cells (Review). In Strauss M, Barranger JA (eds) Concepts in Gene Therapy. DeGruyter, Berlin, pp 233–266Google Scholar
- 9.Baum C, Ostertag W, Stocking C, von Laer D (1998) Retroviral vector design for cancer gene therapy. In Lattime E, Gerson S (eds) Seminars in oncology. Academic Press, San Diego, in press.Google Scholar
- 10.Laer von D, Thomsen S, Vogt B, Donath M, Kruppa J, Rein A, Ostertag W, Stocking C (1998) Entry of amphotropic and 10 Ai pseudotyped murine retroviruses is restricted in hematopoietic stem cell lines. J Virol 72:1424–1430Google Scholar
- 17.Hildinger M, Eckert HG, Schilz AJ, John J, Ostertag W, Baum C (1998) FMEV vectors: both retroviral long terminal repeat and leader are important for high expression in transduced hematopoietic cells. Gene Ther, in pressGoogle Scholar
- 21.Hildinger M, Ostertag W, Abel KL, Baum C (1998) Ideal design of 5’ untranslated sequences in retroviral vectors: high and specific transgene expression with minimal potential for viral recombination. Submitted for publicationGoogle Scholar
- 22.Jelinek J, Rafferty JA, Cmejla R, Hildinger M, Chinnasamy D, Ostertag W, Margison GP, Dexter TM, Fairbairn LJ, Baum C (1998) Transduction of human haemopoietic progenitor cells with a dual function retrovirus expressing multidrug resistance-i and 06-alkylguanine-DNA-alkytransferase confers resistance to multiple chemotherapeutic agents. Submitted for publicationGoogle Scholar
- 24.Hildinger M, Fehse B, Bohn W, Zander AR, Ostertag W, Baum C (1998) Bicistronic retroviral vectors for combining myeloprotection with cell surface marking. Submitted for publicationGoogle Scholar
- 26.Baum C, Itoh K, Meyer J, Laker C, Ito Y, Ostertag W (1997) The potent enhancer activity of SFFVp in hematopoietic cells is governed by a binding site for Spi in the upstream control region and by a unique enhancer core creating an exclusive target for PEBP/CBF. J Virol 71:6323–633PubMedGoogle Scholar