Peptides for Assisting Delivery Across the Blood Brain Barrier

Abstract

The present invention provides compositions and methods useful for delivering agents to target cells or tissues, for example nerve cells and other cells in the central nervous system. The compositions and methods are useful for delivering agents across the blood-brain barrier. The present invention also provides methods of using the compositions provided by the present invention to deliver agents, for example therapeutic agents for the treatment of neurologically related disorders.

1 .- 65 . (canceled) 
     
     
         66 . A composition for targeted delivery of an effector agent to a neuronal cell, astrocyte or microglia cell, comprising an amino acid sequence of SEQ ID NO: 13 or a variant of at least 85% sequence identity to SEQ ID NO: 1, and at least one targeting agent and at least one effector agent. 
     
     
         67 . The composition of  claim 66 , wherein the effector agent is conjugated to the amino acid sequence of SEQ ID NO: 13 or a variant of at least 85% sequence identity to SEQ ID NO: 1. 
     
     
         68 . The composition of  claim 66 , wherein the amino acid sequence of SEQ ID NO: 13 or a variant of at least 85% sequence identity to SEQ ID NO: 1 is present on the surface of a nanoparticle and wherein the effector agent is present on the surface or in the nanoparticle. 
     
     
         69 . The composition of  claim 68 , wherein the nanoparticle is a liposome or polymeric nanoparticle. 
     
     
         70 . The composition of  claim 69 , wherein the liposome or polymeric nanoparticle is a cationic liposome. 
     
     
         71 . The composition of  claim 66 , wherein the effector agent is selected from the group consisting of: a nucleic acid agent, a RNAi agent or a microRNA agent, a small molecule, a protein, peptide, aptamer. 
     
     
         72 . The composition of  claim 71 , wherein the nucleic acid is selected from the group consisting of: RNA, siRNA, mRNA, tRNA, miRNA, shRNA or combinations thereof. 
     
     
         73 . The composition of  claim 71 , wherein the nucleic acid is selected from the group consisting of: DNA, antisense nucleic acids, oligonucleic acids, peptide nucleic acid (PNA), pseudo-complementary PNA (pcPNA), locked nucleic acid (LNA), and antigomirs. 
     
     
         74 . The composition of  claim 66 , wherein the effector agent is an antibody, peptidomimetic monoclonal antibody or avimir. 
     
     
         75 . The composition of  claim 66 , wherein the amino acid sequence of SEQ ID NO: 13 or a variant of at least 85% sequence identity to SEQ ID NO: 1 is conjugated to a cell permeable peptide. 
     
     
         76 . The composition of  claim 75 , wherein the cell permeable peptide is a polymer consisting of arginine residues or is a protamine peptide. 
     
     
         77 . A method for treatment of cancer comprising administering the subject with cancer the composition according to  claim 66 .