Endogenous Gag-based capsids and uses thereof
Nucleic acids encoding endogenous Gag peptides can be isolated from various organisms. Nucleic acids encoding various endogenous Gag polypeptides can be isolated from human DNA. The nucleic acids can be used to express endogenous Gag polypeptides that can be assembled into capsids. Endogenous Gag polypeptides and capsids can be used package cargo and/or deliver it to cells, for example, to package and/or deliver a nucleic acid molecule for use in gene editing, such as a component involved in a CRISPR-Cas system.
1. A composition comprising: (a) a capsid that comprises an endogenous Gag polypeptide, and (b) a nucleic acid molecule for use in gene editing; wherein the nucleic acid molecule for use in gene editing is associated with the capsid, and the endogenous Gag polypeptide is not an Arc polypeptide.
2. The composition of claim 1 , wherein the nucleic acid molecule for use in gene editing encodes or is a component involved in a CRISPR-Cas system.
3. The composition of claim 1 , wherein the nucleic acid molecule for use in gene editing encodes a component involved in a Zinc finger nuclease.
4. The composition of claim 1 , wherein the nucleic acid molecule for use in gene editing encodes a component involved in a transcription activator-like effector nuclease.
5. The composition of claim 1 , wherein the endogenous Gag polypeptide is a human endogenous Gag polypeptide.
6. The composition of claim 1 , wherein the endogenous Gag polypeptide is a Paraneoplastic Ma antigen family polypeptide.
7. The composition of claim 1 , wherein the endogenous Gag polypeptide is a retrotransposon Gag-like family polypeptide.
8. The composition of claim 7 , wherein the retrotransposon Gag-like family polypeptide comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 28.
9. The composition of claim 1 , wherein the endogenous Gag polypeptide is an endogenous Gag polypeptide comprising:
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;
e) 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;
f) 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;
g) 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;
h) 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;
i) 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;
j) an amino acid sequence that is SEQ ID NO: 25 or an amino acid sequence that is at least 90% identical to the SEQ ID NO: 25;
k) an amino acid sequence that is SEQ ID NO: 26 or an amino acid sequence that is at least 90% identical to the SEQ ID NO: 26; or
l) 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.
10. The composition of claim 1 , further comprising a delivery component that comprises an extracellular vesicle, microvesicle, liposome, micelle, or viral envelope glycoprotein.
11. The composition of claim 10 , wherein the delivery component comprises the extracellular vesicle.
12. The composition of claim 10 , wherein the delivery component comprises the liposome.
13. The composition of claim 10 , wherein the delivery component comprises the viral envelope glycoprotein.
14. A polynucleotide comprising a nucleotide sequence encoding the endogenous Gag polypeptide of claim 1 and the nucleic acid molecule for use in gene editing of claim 1 .
15. A method of delivering a gene editing system to a cell comprising administering the composition of claim 1 to the cell.
16. The method of claim 15 , wherein the cell is a eukaryotic cell.
17. The method of claim 15 , wherein the cell is a vertebrate cell.
18. The method of claim 15 , wherein the cell is a mammalian cell.
19. The method of claim 15 , wherein the cell is a human cell.