Recombinant protein-based method for the delivery of silencer RNA to target the brain

摘要: The present invention relates to the design and development of recombinant protein for delivery silencer RNA complex mediate interference since it represents a novel therapeutic approach modulate several neurodegenerative disease-related genes across blood-brain barrier (BBB). To overcome challenges due this biologics other biological complex, describes method wherein peptide having sequence GGGGHLNILSTLWKYRC represented by SEQ ID NO. 1 known target specific gangliosides was linked double-stranded binding bind deliver brain parenchyma. designed fusion comprising RNA-binding domain (dsRBD) human Trans Activation response element (TAR) Binding Protein (TARBP2) targeting that binds GM1. Conformation-specific TARBP2 results in formation homogenous serum-stable with GM1 potential. Uptake neural cells reveals selective requirement entry. Remarkably, pertains systemic TARBP-BTP AβPP-PS1 mouse model Alzheimer's disease (AD) led distinctive localization primarily cerebral hemisphere hippocampus cortex principle can work mammalian CNS targets. Further, silencer-RNA mediated significant knockdown BACE1, protease both wild type C57BL/6 mice. establishes emergent importance proteins delivering siRNA as simple tissues treat diseases besides (AD). is also useful study gene function hitherto unidentified genes/interplay systems central nervous system.