Extracellular vesicle-based diagnostics and engineered exosomes for targeted therapeutics against cancer
This invention is related to use of exosomes for biomarker analysis for early detecting and characterizing of disease progression of cancer. Further, the invention provides bioengineered exosomes for use in methods of targeting and treating cancer.
1. A method of bioengineering exosomes for targeting cancer cells, the method comprising:
(a) expressing a XPepα fusion protein encoded by SEQ ID NO:2 in a host cell;
(b) isolating secreted exosomes comprising the fusion protein; and
(c) loading the isolated exosomes with a least one RNA oligonucleotide or chemotherapeutic agent.
2. The method of claim 1 , wherein step (a) comprises transducing the host cell with a viral vector encoding the fusion protein.
3. A bioengineered exosome made by the method of claim 1 .
4. A therapeutic bioengineered exosome comprising a XPepα fusion protein encoded by SEQ ID NO:2.
5. The therapeutic bioengineered exosome of claim 4 further comprising at least one RNA oligonucleotide or chemotherapeutic agent.
6. The therapeutic bioengineered exosome of claim 5 , wherein the RNA oligonucleotide is a siRNA or miRNA specific for cancer.
7. The therapeutic bioengineered exosome of claim 6 , wherein the cancer is breast cancer and wherein the miRNA is miR-200, miR30c, or miR206.
8. A method of treating a patient with cancer, the method comprising administering an effective amount of the therapeutic bioengineered exosome of claim 5 to the patient with cancer.
9. The method of claim 8 , wherein the patient has a solid tumor cancer.
10. The method of claim 1 , wherein step (c) comprises loading the at least one RNA oligonucleotide or chemotherapeutic agent by electroporation of the exosomes.
11. The method of claim 1 , wherein the RNA oligonucleotide is a siRNA or miRNA specific for breast cancer.
12. The method of claim 8 , wherein the cancer is breast cancer and wherein the at least one RNA oligonucleotide is a miRNA selected from the group consisting of miR-200, miR30c, and miR206.