Vault complexes for facilitating biomolecule delivery
The invention relates to compositions of vault complexes containing recombinant membrane lytic proteins, such as an adenovirus protein VI lytic domain, and methods of using the vault complexes to facilitate delivery and entry of a biomolecule into a cell or subject.
1. A vault-like particle comprising a modified major vault protein (MVP), wherein the modified MVP comprises a membrane lytic peptide sequence added to the N-terminus of the modified MVP, wherein the modified MVP further comprises an antibody binding domain which is a Z-domain.
2. The vault-like particle of claim 1 , wherein said membrane lytic peptide sequence comprises the membrane lytic domain of adenovirus VI (pVI).
3. The vault-like particle of claim 1 , wherein the membrane lytic peptide sequence comprises SEQ ID NO:3.
4. The vault-like particle of claim 1 , wherein the membrane lytic peptide sequence comprises SEQ ID NO:4.
5. The vault-like particle of claim 1 , wherein the modified MVP further comprises an EGF domain.
6. The vault-like particle of claim 5 , wherein the EGF domain is added to the C-terminus of the modified MVP.
7. The vault-like particle of claim 1 , wherein the Z-domain is added to the C-terminus of the modified MVP.
8. The vault-like particle of claim 1 , further comprises a vault poly ADP-ribose polymerase (VPARP), a telomerase vault associated protein 1 (TEP 1), or an untranslated RNA molecule (vRNA).
9. A vault-like particle comprising a modified major vault protein (MVP), wherein the modified MVP comprises a membrane lytic peptide sequence added to the N-terminus of the modified MVP, wherein the modified MVP further comprises an EGF domain.
10. The vault-like particle of claim 9 , wherein the EGF domain is added to the C-terminus of the modified MVP.
11. The vault-like particle of claim 9 , wherein said membrane lytic peptide sequence comprises the membrane lytic domain of adenovirus VI (pVI).
12. The vault-like particle of claim 9 , wherein the membrane lytic peptide sequence comprises SEQ ID NO:3.
13. The vault-like particle of claim 9 , wherein the membrane lytic peptide sequence comprises SEQ ID NO:4.
14. The vault-like particle of claim 9 , wherein the vault-like particle further comprises a vault poly ADP-ribose polymerase (VPARP), a telomerase vault associated protein 1 (TEP 1), or an untranslated RNA molecule (vRNA).
15. The vault-like particle of claim 9 , wherein the modified MVP further comprises an antibody binding domain.
16. The vault-like particle of claim 15 , wherein the antibody binding domain is a Z-domain.
17. A method of delivering a substance to a cell, comprising introducing the vault-like particle of claim 9 to the cell, wherein the vault-like particle comprises said substance.