Antibody derivatives for controlling gene expression

Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Blood proteins or globulins – e.g. – proteoglycans – platelet...

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C07K 1646

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active

059945125

ABSTRACT:
The present invention is directed to methods and compositions useful for altering the transcriptional expression of genes in eukaryotic cells. The invention employs novel antibody derivative molecules which function to recognize and bind to specific cis-regulatory DNA sequence elements of a eukaryotic gene. When two antibody derivative molecules are bound to adjacent cis-regulatory DNA sequence elements of a gene, those molecules may interact to form an antibody binding site which is capable of recognizing and binding to a transcription factor protein for the target gene, thereby affecting the functionality of that transcription factor protein and, in turn, the transcriptional activity of the gene. Also provided herein are isolated nucleic acids encoding the novel antibody derivative molecules of the present invention and expression vectors comprising those nucleic acids.

REFERENCES:
Beerli, R.R., et al., "Autocrine Inhibition of the Epidermal Growth Factor Receptor by Intracellular Expression of a Single-Chain Antibody," Biochemical and Biophysical Research Communications 204(2):666-672 (1994).
Beerli, R.R., et al., "Intracellular Expression of a Single Chain Antibodies Reverst ErbB-2 Transformation," The Journal of Biological Chemistry, 269(39):23931-23936 (1994).
Biocca, S., et al., "Expression and Targeting of Intracellular Antibodies in Mammalian Cells," The EMBO Journal, 9(1):101-108 (1990).
Kabat, E.A., Recombination of Separated Chains to Form IgG, Structural Concepts in Immunology and Immunochemistry (2nd Ed.), Holt, Rinehart ad Winston:New York (1976) pp. 248-252.
Marasco, W.A., et al., "Design, Intracellular Expression, and Activity of a Human Anti-Human Immunodeficiency Virus Type 1 gp120 Single-Chain Antibody," Proc. Natl. Acad. Sci. USA, 90:7889-7893 (1993).
Biocca et al. Expression and targetingt of intracellular antibodies in mammalian cells. EMBO J. vol. 9 pp. 101-108, 1990.

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