Abstract: The present invention provides for compositions and methods for in vivo delivery of a cell-permeable complex to cells of the central nervous system, wherein the cell-permeable complex decreases the level of a functional target protein encoded by a target mRNA molecule. In preferred embodiments of the invention, the cell-permeable complex comprises an siRNA nucleic acid molecule operably linked to a cell-penetrating peptide, wherein the cell-penetrating peptide facilitates transport of the cell-permeable complex across both the blood brain barrier and cell membrane of a target cell. The methods of the invention further encompass the utilization of convection-enhanced delivery methods such as intracerebral clysis (ICC) to deliver the cell-permeable complex to the target cells of the central nervous system.