Abstract: Disclosed herein are multimeric molecular complexes and compounds that are multivalent, i.e., they have two or more targeting elements directed to a ligand that confers paracellular transporting properties and/or transcytotic properties to complexes and compounds to which it is bound. The complexes and compounds have properties that are different from the properties of monomers, complexes and compounds having only one targeting element directed to a paracellular and/or transcytotic ligand. The complexes and compounds of the invention undergo endocytosis, transcytosis and exocytosis; following endocytosis, the complexes or compounds may be transported into the cytosol or an organelle of a cell. In polarized cells, transcytosis can proceed in a “forward” or “reverse” direction. Reverse transcytosis is used for the non-invasive delivery of biologically active agents from the lumen of, e.g., the gastrointestinal tract or the airways of lungs, to the circulatory system.

Abstract: Disclosed herein are complexes and compounds that pass through cellular barriers to deliver compounds into, through and out of cells, and methods of producing and using such complexes and compounds. The complexes and compounds of the invention comprise a biologically active portion and a targeting element directed to a ligand that confers transcellular, transcytotic or paracellular transporting properties to an agent specifically bound to the ligand, with the proviso that the targeting element is not an antibody. Also disclosed are complexes and compounds that comprise two or more targeting elements directed to a ligand that confers transcellular, transcytotic or paracellular transporting properties to an agent specifically bound to the ligand. Preferred ligands include but are not limited to the stalk of pIgR, a pIgR domain, an amino acid sequence that is conserved among pIgR's from different animals, and one of several regions of pIgR defined herein.