Lipopeptide delivery of siRNA to the central nervous system.

RNA interference is a relatively new tool used to silence specific genes in diverse biological systems. The development of this promising new technique for research and therapeutic use in studying and treating neurological diseases has been hampered by the lack of an efficient way to deliver siRNA transvascularly across the blood-brain barrier (BBB) to the central nervous system (CNS). Here we describe a method for delivering siRNA to the CNS by complexing it to a peptide that acts as a neuronal address by binding to acetylcholine receptors (AchRs). Adding cationic liposomes to the complex protects it from serum nucleases and proteases en route. When injected intravenously, these liposome-siRNA-peptide complexes resist serum degradation, effectively cross the BBB, and deliver siRNA to AchR-expressing cells to suppress protein expression in the CNS.