Endogenous Gag-based capsids and uses thereof
Disclosed herein, in certain embodiments, are recombinant Arc and endogenous Gag polypeptides, and methods of using recombinant Arc and endogenous Gag polypeptides.
1. A capsid comprising a recombinant endogenous Gag polypeptide and a heterologous cargo that is not native to the endogenous Gag polypeptide, wherein the endogenous Gag polypeptide is not an Arc polypeptide.
2. The capsid of claim 1 , wherein the endogenous Gag polypeptide is a Paraneoplastic Ma antigen family polypeptide.
3. The capsid of claim 2 , wherein the Paraneoplastic Ma antigen family polypeptide comprises:
a) an amino acid sequence that is SEQ ID NO: 16 or an amino acid sequence that is at least 90% identical to the SEQ ID NO: 16;
b) an amino acid sequence that is SEQ ID NO: 17 or an amino acid sequence that is at least 90% identical to the SEQ ID NO: 17;
c) an amino acid sequence that is SEQ ID NO: 18 or an amino acid sequence that is at least 90% identical to the SEQ ID NO: 18;
d) an amino acid sequence that is SEQ ID NO: 19 or an amino acid sequence that is at least 90% identical to the SEQ ID NO: 19; or
e) an amino acid sequence that is SEQ ID NO: 27 or an amino acid sequence that is at least 90% identical to the SEQ ID NO: 27.
4. The capsid of claim 2 , wherein the heterologous cargo is a nucleic acid.
5. The capsid of claim 4 , wherein the heterologous cargo is an RNA.
6. The capsid of claim 2 , wherein the heterologous cargo is a therapeutic agent.
7. The capsid of claim 2 , wherein the heterologous cargo is a polypeptide.
8. The capsid of claim 2 , wherein the heterologous cargo is a gene editing system.
9. The capsid of claim 2 , further comprising a second polypeptide.
10. The capsid of claim 9 , wherein the second polypeptide is an antibody or binding fragment thereof.
11. The capsid of claim 9 , wherein the second polypeptide binds to a target site.
12. The capsid of claim 2 , further comprising a delivery component that comprises a microvesicle, a microparticle, a liposome, or a micelle.
13. The capsid of claim 2 , further comprising a delivery component that comprises an extracellular vesicle.
14. The capsid of claim 1 , wherein the endogenous Gag polypeptide is a retrotransposon Gag-like family polypeptide.
15. The capsid of claim 14 , wherein the retrotransposon Gag-like family polypeptide comprises:
a) an amino acid sequence that is SEQ ID NO: 20 or an amino acid sequence that is at least 90% identical to the SEQ ID NO: 20;
b) an amino acid sequence that is SEQ ID NO: 21 or an amino acid sequence that is at least 90% identical to the SEQ ID NO: 21;
c) an amino acid sequence that is SEQ ID NO: 22 or an amino acid sequence that is at least 90% identical to the SEQ ID NO: 22;
d) an amino acid sequence that is SEQ ID NO: 23 or an amino acid sequence that is at least 90% identical to the SEQ ID NO: 23;
e) an amino acid sequence that is SEQ ID NO: 24 or an amino acid sequence that is at least 90% identical to the SEQ ID NO: 24; or
f) an amino acid sequence that is SEQ ID NO: 28 or an amino acid sequence that is at least 90% identical to the SEQ ID NO: 28.
16. The capsid of claim 14 , wherein the heterologous cargo is a nucleic acid.
17. The capsid of claim 16 , wherein the heterologous cargo is an RNA.
18. The capsid of claim 14 , wherein the heterologous cargo is a therapeutic agent.
19. The capsid of claim 14 , wherein the heterologous cargo is a polypeptide.
20. The capsid of claim 14 , wherein the heterologous cargo is a gene editing system.
21. The capsid of claim 14 , further comprising a second polypeptide.
22. The capsid of claim 21 , wherein the second polypeptide is an antibody or binding fragment thereof.
23. The capsid of claim 21 , wherein the second polypeptide binds to a target site.
24. The capsid of claim 14 , further comprising a delivery component that comprises a microvesicle, a microparticle, a liposome, or a micelle.
25. The capsid of claim 14 , further comprising a delivery component that comprises an extracellular vesicle.