Biological agent-exosome compositions and uses thereof
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. 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 a neurotrophin, wherein the exosome is isolated from a macrophage/monocyte.
2. The composition of claim 1 , wherein the exosome further comprises a targeting agent.
3. The composition of claim 2 , wherein the targeting agent is attached to the surface of the exosome.
4. The composition of claim 3 , wherein the targeting agent is attached using a polymeric linker.
5. The composition of claim 4 , wherein the polymer linker is a water soluble polymer liker.
6. The composition of claim 2 , wherein the targeting agent or polymeric linker is connected to a lipid group in or on the exosome.
7. The composition of claim 1 , wherein the exosome is modified with a molecule containing multiple charges.
8. The composition of claim 7 , wherein the molecule containing multiple charges is a polyion or a lipid.
9. The composition of claim 1 , further comprising a pharmaceutically acceptable carrier.
10. A method of delivering a biological agent to a cell, comprising contacting the cell with the composition of claim 1 , thereby delivering the biological agent to the cell.
11. A method of enhancing delivery of a biological agent to a cell in a tumor microenvironment, to a cancer cell, or to a central nervous system cell, comprising contacting the cell with the composition of claim 1 , thereby enhancing delivery of the biological agent to the cell relative to the delivery of the biological agent in the absence of an exosome.
12. 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 1 to the subject, thereby delivering the biological agent to the subject.
13. A method of treating a disorder in a subject in need thereof, comprising delivering a therapeutically effective amount of the composition of claim 1 to the subject, wherein the biological agent is effective for treating the disorder, thereby treating the disorder in the subject.
14. The composition of claim 1 , wherein the neurotrophin is brain derived neurotrophic factor, nerve growth factor, neurotrophin 3, neurotrophin 4, glial cell derived neurotrophic factor, artemin, neurturin, persephin, or ciliary neurotrophic factor.