Vault and vault like carrier molecules
A method of using vaults as carrier molecules to deliver one or more than one substance to an organism, or to a specific tissue or to specific cells, or to an environmental medium. A vault-like particle. A method of preventing damage by one or more than one substance to an organism, to a specific tissue, to specific cells, or to an environmental medium, by sequestering the one or more than one substance within a vault-like particle. A method of delivering one or more than one substance or a sensor to an organism, to a specific tissue, to specific cells, or to an environmental medium. According to another embodiment of the present invention, there is provided a method of making vault-like particles, and making vault-like particles comprising one or more than one substance, or one or more than one sensor.
1. A method of delivering at least one substance to an organism, comprising administering to the organism an assembled vault-like particle, wherein said assembled vault-like particle comprises:
i) multiple copies of a naturally occurring sequence of major vault protein (MVP) having an N-terminal and a C-terminal and having at least one modification selected from the group consisting of addition of an amino acid sequence to the N-terminal, addition of an amino acid sequence to the C-terminal, deletion of between 1 to 100 amino acid residues from the C-terminal, deletion of between 1 to 100 amino acid residues from the N-terminal, and substitution of at least one amino acid residue of the naturally occurring sequence of MVP, and
ii) the at least one substance.
2. The method of claim 1 , wherein the at least one modification is the addition of an amino acid sequence to the N-terminal or the addition of an amino acid sequence to the C-terminal.
3. The method of claim 1 , wherein the at least one modification is the addition of an amino acid sequence to the N-terminal, which results in at least one substance-binding domain within the assembled vault-like particle.
4. The method of claim 3 , wherein the at least one substance-binding domain within the assembled vault-like particle is at least one polynucleotide-binding domain.
5. The method of claim 1 , wherein the at least one modification is the addition of an amino acid sequence to the N-terminal, which results in at least one substance-binding domain within the assembled vault-like particle, and the addition of an amino acid sequence to the C-terminal, which results in at least one binding domain.
6. The method of claim 5 , wherein the at least one binding domain is a receptor-binding domain.
7. The method of claim 6 , wherein the at least one receptor-binding domain is specific and wherein the administering is to a specific tissue or to specific cells.
8. The method of claim 1 , wherein the at least one modification is the addition of an amino acid sequence to the C-terminal, which results in at least one binding domain.
9. The method of claim 8 , wherein the at least one binding domain is a receptor-binding domain.
10. The method of claim 9 , wherein the at least one receptor-binding domain is specific and wherein the administering is to a specific tissue or to specific cells.
11. The method of claim 1 , wherein the at least one substance is selected from the group consisting of an enzyme, a pharmaceutical agent, a plasmid, a polynucleotide, a polypeptide, and a sensor.
12. The method of claim 1 , wherein the administering is to a human.
13. The method of claim 1 , wherein the assembled vault-like particle further comprises a naturally occurring sequence of VPARP, a portion of the naturally occurring sequence of VPARP comprising at least about 150 consecutive residues from residue 1473 to residue 1724 of VPARP SEQ ID NO: 3, or an intraspecies variation in the sequence thereof in the assembled vault-like particle, wherein the naturally occurring sequence of VPARP or the portion of the naturally occurring sequence of VPARP has at least one modification selected from the group consisting of addition of an amino acid sequence to the C-terminal of the naturally occurring sequence of VPARP or the portion of the naturally occurring sequence of VPARP and addition of an amino acid sequence to the N-terminal of the naturally occurring sequence of VPARP or the portion of the naturally occurring sequence of VPARP.
14. A method of delivering at least one substance to an organism, comprising administering to the organism an assembled vault-like particle, wherein the assembled vault-like particle comprises:
i) multiple copies of a naturally occurring sequence of MVP or a naturally occurring sequence of MVP having an N-terminal and a C-terminal and having at least one modification selected from the group consisting of addition of an amino acid sequence to the C-terminal, addition of an amino acid sequence to the N-terminal, deletion of between 1 to 100 amino acid residues from the C-terminal, deletion of between 1 to 100 amino acid residues from the N-terminal, and substitution of at least one amino acid residue of the naturally occurring sequence of MVP,
ii) a naturally occurring sequence of VPARP, a portion of the naturally occurring sequence of VPARP comprising at least about 150 consecutive residues from residue 1473 to residue 1724 of VPARP SEQ ID NO: 3, or an intraspecies variation in the sequence thereof in the assembled vault-like particle, wherein the naturally occurring sequence of VPARP or the portion of the naturally occurring sequence of VPARP has at least one modification selected from the group consisting of addition of an amino acid sequence to the C-terminal of the naturally occurring sequence of VPARP or the portion of the naturally occurring sequence of VPARP and addition of an amino acid sequence to the N-terminal of the naturally occurring sequence of VPARP or the portion of the naturally occurring sequence of VPARP, and
iii) the at least one substance.
15. The method of claim 14 , wherein the portion of the naturally occurring sequence of VPARP comprises residues from about residue 1562 to about residue 1724 of SEQ ID NO: 3.
16. The method of claim 15 , wherein the portion of the naturally occurring sequence of VPARP comprises residues from about residue 1473 to about residue 1724 of SEQ ID NO: 3.
17. The method of claim 14 , wherein the at least one modification of ii) is the addition of an amino acid sequence to the C-terminal of the naturally occurring sequence of VPARP or the portion of the naturally occurring sequence of VPARP.
18. The method of claim 14 , wherein the at least one modification of ii) is the addition of an amino acid sequence to the N-terminal of the naturally occurring sequence of VPARP or the portion of the naturally occurring sequence of VPARP.
19. The method of claim 14 , wherein the at least one modification of ii) is the addition of an amino acid sequence to the C-terminal of the naturally occurring sequence of VPARP or the portion of the naturally occurring sequence of VPARP and the addition of an amino acid sequence to the N-terminal of the naturally occurring sequence of VPARP or the portion of the naturally occurring sequence of VPARP.
20. The method of claim 14 , wherein the at least one modification of i) is the addition of an amino acid sequence to the C-terminal of the naturally occurring sequence of MVP.
21. The method of claim 14 , wherein the at least one modification of i) is the addition of an amino acid sequence to the N-terminal of the naturally occurring sequence of MVP.
22. The method of claim 14 , wherein the at least one modification of i) is the addition of an amino acid sequence to the C-terminal of the naturally occurring sequence of MVP and the addition of an amino acid sequence to the N-terminal of the naturally occurring sequence of MVP.
23. The method of claim 14 , wherein the at least one substance is selected from the group consisting of an enzyme, a pharmaceutical agent, a plasmid, a polynucleotide, a polypeptide, and a sensor.
24. The method of claim 14 , wherein the administering is to a human.