Targeted delivery of genes encoding secretory proteins

摘要

Molecular complexes for targeting a gene encoding a secretory protein to a specific cell in vivo and obtaining secretion of the protein by the targeted cell are disclosed. An expressible gene encoding a desired secretory protein is complexed to a conjugate of a cell-specific binding agent and a gene-binding agent. The cell-specific binding agent is specific for a cellular surface structure which mediates internalization of ligands by endocytosis. An example is the asialoglycoprotein receptor of hepatocytes. The gene-binding agent is a compound such as a polycation which stably complexes the gene under extracellular conditions and releases the gene under intracellular conditions so that it can function within a cell. The molecular complex is stable and soluble in physiological fluids and can be used in gene therapy to selectively transfect cells in vivo to provide for production and secretion of a desired secretory protein.