Abstract
The development of vectors for target-cell specific gene delivery is a major goal of gene therapeutic strategies. Thereby non-viral gene delivery vectors are gaining increasing interest [1]. Progress has been made in the understanding how individual activities of viruses can be mimicked and methodologies have been developed which allow to combine different functions required for gene transfer into an artificial complex. An attractive approach for the design of such modular self-assembling systems for gene delivery is based on fusion proteins engineered to incorporate in a single polypeptide chain several cooperating functions [2–4]. Each of these domains can account for a distinct activity required for DNA-binding, cell recognition and intracellular delivery. Such fusion proteins in contrast to similar chemical conjugates can be produced in suitable expression systems in their final form and the resulting products are generally homogeneous in their composition.
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References
Cooper, M. J. Noninfectious gene transfer and expression systems for cancer gene therapy. Semin. Oncol. 23: 172–187, 1996.
Chen, S. Y., Zani, C., Khouri, Y., and Marasco, W. A. Design of a genetic immunotoxin to eliminate toxin immunogenicity. Gene Ther. 2: 116–123, 1995.
Fominaya, J. and Wels, W. Target cell-specific DNA transfer mediated by a chimeric multidomain protein. Novel non-viral gene delivery system. J. Biol. Chem. 271: 10560–10568, 1996.
Paul, R. W., Weisser, K. E., Loomis, A., Sloane, D. L., LaFoe, D., Atkinson, E. M., and Overell, R. W. Gene transfer using a novel fusion protein, GAL4/invasin. Hum. Gene Ther. 8: 1253–1262, 1997.
Hwang, J., Fitzgerald, D. J., Adhya, S., and Pastan, I. Functional domains of Pseudomonas exotoxin identified by deletion analysis of the gene expressed in E. coli. Cell. 48: 129–136, 1987.
Choe, S., Bennett, M. J., Fujii, G., Curmi, P. M., Kantardjieff, K. A., Collier, R. J., and Eisenberg, D. The crystal structure of diphtheria toxin. Nature. 357: 216–222, 1992.
Wels, W., Groner, B., and Hynes, N. E. Intervention in receptor tyrosine kinase-mediated pathways: recombinant antibody fusion proteins targeted to ErbB2. Curr. Top. Microbiol. Immunol. 213: 113–128, 1996.
Novoa, I., Gotten, M., and Carrasco, L. Hybrid proteins between Pseudomonas aeruginosa exotoxin A and poliovirus 2Apro cleave p220 in HeLa cells. J. Virol. 70: 3319–3324, 1996.
Carey, M., Kakidani, H., Leatherwood, J., Mostashari, F., and Ptashne, M. An aminoterminal fragment of GAL4 binds DNA as a dimer. J. Mol. Biol. 209: 423–432, 1989.
Wagner, E., Cotten, M., Foisner, R., and Birnstiel, M. L. Transferrin-polyeation-DNA complexes: the effect of polycations on the structure of the complex and DNA delivery to cells. Proc. Natl. Acad. Sci. USA. 88: 4255–4259, 1991.
Wels, W. and Fominaya, J. Peptides and fusion proteins as modular DNA carriers. In L. W. Seymour, A. V. Kabanov, and P. L. Feigner (eds.), Self-assembling complexes for gene delivery: from chemistry to clinical trial. John Wiley & Sons Ltd., New York: 1998, in press.
Fisher, K. J. and Wilson, J. M. The transmembrane domain of diphtheria toxin improves molecular conjugate gene transfer. Biochem. J. 321: 49–58, 1997.
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© 1998 Springer-Verlag Berlin Heidelberg
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Uherek, C., Fominaya, J., Wels, W. (1998). Modular Fusion Proteins for Receptor-mediated Gene Delivery. In: Xanthopoulos, K.G. (eds) Gene Therapy. NATO ASI Series, vol 105. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-72160-1_17
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DOI: https://doi.org/10.1007/978-3-642-72160-1_17
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