Targeted delivery of poly- or oligonucleotides to cells

摘要

Molecular complexes for targeting oligonucleotides, such as antisense oligonucleotides or ribozymes, to a specific cell to block expression of a gene or genes in the cell are described. The single-stranded poly- or oligonucleotide is complexed to a conjugate of a cell-specific binding agent and a poly- or oligonucleotide-binding agent. The cell-specific binding agent is specific for a cellular surface structure which mediates internalization of the complex. An example is the asialoglycoprotein receptor of hepatocytes. The poly- or oligodeoxy-nucleotide-binding agent is a compound such as a polycationic protein which stably complexes the oligonucleotide under extracellular conditions and releases it under intracellular conditions so that it can hybridize with the target RNA. The molecular complex is stable and soluble in physiological fluids and can be used to selectively introduce antisense oligonucleotides, ribozymes or other single-stranded oligonucleotides into a cell to inhibit expression of a gene within the cell. The oligonucleotide can be directed against cellular genes (e.g., cellular oncogenes) or genes of noncellular origin (e.g., viral oncogenes, genes of an infecting pathogen).