<span>Background of the invention: The epithelium is the first line of defense against a variety of pathogens. Epithelial cells produce low molecular weight antimicrobial peptides, antibacterial enzymes, and antiproteases. Optimal methods of specifically targeting therapeutic molecules to epithelial cells have been lacking in the art. There is a continuing need in the art for methods of providing therapeutic agents to respiratory epithelia cells in diseases such as cyptic fibrosis, asthma, and emphysema, and to intestinal epithelial cells, for example, in inflammatory bowel diseases. Summary of the invention: It is an object of the invention to provide bifunctional molecules useful for delivery of therapeutic molecules and methods for delivering therapeutic molecules to cells. These and other objects of the invention are provided by one or more embodiments as described below. In one embodiment the invention provides a fusion protein. The fusion protein comprises a single chain Fv molecule directed against a human transcytotic receptor covalently linked to a therapeutic protein. The therapeutic protein may be, for example, .alpha..sub.1 -antitrypsin, a cytokine, such as interleukin-2 or interleukin-10, or a peptide antibiotic. Suitable peptide antibiotics include aerosporin, amphomycin, aspartocin, bacitracins, caperomycins, colistins, dactinomycins, glumamycins, gramicidin D, gramicidin S, mikamycin B, polymixins, pristinamycin, siomycin, staphylomycin S, thiostrepton, tyrocidines, tyrothricin, </span><span>valinomycin, vancomycin, veramycin B. Any therapeutic protein which one wants delivered to epithelial cells may be used. The fusion protein may further comprise a linker region of less than 50, 40, 30, 20, or 10 amino acid residues. The linker can be covalently linked to and between the single chain Fv molecule and the therapeutic protein. Also provided according to another aspect of the invention is a method of delivering a therapeutic protein to an epithelial cell. The method comprises: administering a fusion protein as described above to a patient, whereby the therapeutic protein is delivered to an epithelial cell. The epithelial cell may be an airway epithelial cell or an intestinal lumen cell, for example. The liver may also be targeted. The administration mode may be any known in the art. However, inhalation and intravenous administration have been found to be both convenient and efficient.Nucleic acid molecules are also provided by the present invention. These encode a fusion protein comprising a single chain Fv molecule directed against a transcytotic receptor covalently linked to a therapeutic protein. The therapeutic protein may be, for example, .alpha..sub.1 -antitrypsin, a cytokine, such as interleukin-2 or interleukin-10, or a peptide antibiotic. Any therapeutic protein which one wants delivered to epithelial cells may be used. The fusion protein may further comprise a linker region of less than 50, 40, 30, 20, or 10 amino acid residues.http://www.google.com/patents?vid=USPAT6261787</span>
