Biological agent-exosome compositions and uses thereof

Abstract

The present invention relates to compositions comprising exosomes and biological agents and methods of using the compositions for the delivery of biological agents to cells and to subjects.

1 - 72 . (canceled) 
     
     
         73 . A composition for delivery of a biological agent to a cell, the composition comprising an exosome comprising the biological agent, wherein the biological agent is not naturally present in the exosome and is an enzyme. 
     
     
         74 . The composition of  claim 73 , wherein the exosome is isolated from a macrophage/monocyte. 
     
     
         75 . The composition of  claim 73 , wherein the enzyme is an enzyme associated with a lysosomal storage disorder (LSD). 
     
     
         76 . The composition of  claim 75 , wherein the enzyme associated with an LSD is lysosome-associated membrane protein 2 (Lamp2b), acid α-glucosidase (GAA), acid sphingomyelinase, iduronate-2-sulfatase (I2S), α-L-iduronidase (IDU), β-hexosaminidase A (HexA), acid β-glucocerebrosidase, N-acetylgalactosamine-4-sulfatase, or α-galactosidase A. 
     
     
         77 . The composition of  claim 73 , wherein the exosome further comprises a targeting agent. 
     
     
         78 . The composition of  claim 77 , wherein the targeting agent is attached to the surface of the exosome. 
     
     
         79 . The composition of  claim 78 , wherein the targeting agent is attached using a polymeric linker. 
     
     
         80 . The composition of  claim 79 , wherein the polymer linker is a water soluble polymer linker. 
     
     
         81 . The composition of  claim 79 , wherein the targeting agent or polymeric linker is connected to a lipid group in or on the exosome. 
     
     
         82 . The composition of  claim 73 , wherein the exosome is modified with a molecule containing multiple charges. 
     
     
         83 . The composition of  claim 82 , wherein the molecule containing multiple charges is a polyion or a lipid. 
     
     
         84 . The composition of  claim 73 , further comprising a pharmaceutically acceptable carrier. 
     
     
         85 . A method of delivering a biological agent to a subject, across the blood brain barrier of a subject, or to inflamed tissue of a subject, comprising delivering the composition of  claim 73  to the subject, thereby delivering the biological agent to the subject. 
     
     
         86 . A method of treating a lysosomal storage disease (LSD) in a subject in need thereof, comprising delivering a therapeutically effective amount of the composition of  claim 75  to the subject, wherein the biological agent is effective for treating of the LSD, thereby treating the LSD in the subject. 
     
     
         87 . The method of  claim 86 , wherein the LSD is Gaucher's disease, Pompe disease, Niemann-Pick, Hunter syndrome (MPS II), Mucopolysaccharidosis I (MPS I), GM2-gangliosidoses, Gaucher disease, Sanfilippo syndrome (MPS IIIA), Tay-Sachs disease, Sandhoff's disease, Krabbe's disease, metachromatic leukodystrophy, or Fabry disease. 
     
     
         88 . The method of  claim 86 , wherein the enzyme associated with an LSD is lysosome-associated membrane protein 2 (Lamp2b), acid α-glucosidase (GAA), acid sphingomyelinase, iduronate-2-sulfatase (I2S), α-L-iduronidase (IDU), β-hexosaminidase A (HexA), acid β-glucocerebrosidase, N-acetylgalactosamine-4-sulfatase, or α-galactosidase A.