Vesicles comprising a pten inhibitor and uses of same

Abstract

The present invention provides pharmaceutical compositions comprising membrane vesicles, including extracellular vesicles including those referred to as exosomes, loaded with an exogenous Phosphatase and tensin homolog (PTEN) inhibitor. Methods of treating neurological diseases, disorders or conditions using the extracellular vesicles are provided. Isolated extracellular vesicles loaded with an exogenous Phosphatase and tensin homolog (PTEN) inhibitor are provided as well.

What is claimed: 
     
         1 . A method of treating a neurological disease, disorder or condition in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of extracellular vesicles loaded with an exogenous inhibitor of phosphatase and tensin homolog (PTEN) expression selected from siRNA targeting PTEN mRNA and shRNA targeting PTEN mRNA, wherein the extracellular vesicles are derived from bone-marrow-derived mesenchymal stem cells (MSCs). 
     
     
         2 . The method according to  claim 1 , wherein the condition is neuronal injury or damage. 
     
     
         3 . The method according to  claim 2 , wherein the neuronal injury or damage is a spinal cord injury (SCI). 
     
     
         4 . The method according to  claim 2 , wherein the neuronal injury or damage is a traumatic injury or damage. 
     
     
         5 . The method according to  claim 1 , wherein the extracellular vesicles are selected from exosomes, microvesicles, ectosomes, exovesicles and a combination thereof. 
     
     
         6 . The method according to  claim 1 , wherein the inhibitor of PTEN expression is selected from (i) an siRNA comprising a nucleic acid sequence selected from SEQ ID NOs: 10, 11, 2, 3, 4 and 5; (ii) an siRNA targeting a nucleic acid sequence selected from SEQ ID NOs: 6 and 7; and (iii) an siRNA comprising a nucleic acid variants of (i) and (ii) having at least 80% sequence identity to the original sequence. 
     
     
         7 . The method according to  claim 1 , wherein said inhibitor of PTEN expression further comprises a hydrophobic moiety. 
     
     
         8 . The method according to  claim 7 , wherein said hydrophobic moiety is selected from the group consisting of a sterol, a ganglioside, a lipid, a vitamin, a fatty acid, a hydrophobic peptide, and a combination thereof, optionally wherein the sterol is cholesterol. 
     
     
         9 . The method according to  claim 1 , wherein the extracellular vesicles are isolated extracellular vesicles composition. 
     
     
         10 . The method according to  claim 1 , wherein the method further comprising administering chondroitinase ABC. 
     
     
         11 . The method according to  claim 1 , wherein the extracellular vesicles are administered in an administration route selected from intranasal, intra-lesion, intrathecal, intravenous, intramuscular, subcutaneous, sublingual, oral, and intracerebral administration route. 
     
     
         12 . The method according to  claim 2 , wherein the extracellular vesicles are administered in an administration route selected from intranasal, intra-lesion, intrathecal, intravenous, intramuscular, subcutaneous, sublingual, oral, and intracerebral administration route. 
     
     
         13 . The method according to  claim 1 , wherein the extracellular vesicles are administered intranasally. 
     
     
         14 . The method according to  claim 2 , wherein the extracellular vesicles are administered intranasally.