Conjugates for delivery to mitochondria
AssigneeThe Forsyth Institute
InventorsHeike Boisvert, Margaret Duncan
Life of this patent
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Abstract
The present disclosure relates generally to conjugates and their uses and production. More particularly, it concerns conjugates comprising an A44 or K39 gingipain adhesion peptide, or fragment thereof (e.g., an A44/K39 peptide portion) covalently attached to a heterologous agent that is capable of entering a cell by endocytosis and translocating to mitochondria.
Claims63
A conjugate comprising
- i) an A44/K39 peptide portion capable of entering a cell by endocytosis and translocating to mitochondria, and
- ii) a heterologous agent covalently associated therewith, wherein the heterologous agent is not a fluorescent protein or a fluorescent dye;
- and
- wherein the conjugate does not comprise a catalytic domain of a gingipain protein.
The conjugate of any proceeding claim, wherein (i) comprises a fragment of an A44 or K39 peptide capable of entering a cell by endocytosis and translocating to mitochondria.
The conjugate of any proceeding claim, wherein the fragment of an A44 or K39 peptide comprises at least 50 amino acid residues.
The conjugate of any proceeding claim, wherein the conjugate does not include a full length, native A44 or K39 peptide.
The conjugate of any proceeding claim, wherein neither (i) nor the conjugate comprise the amino acid sequence set forth in SEQ ID NO.:
- 1 and/or SEQ ID NO.:
- 2.
The conjugate of any proceeding claim, wherein, if the conjugate comprises an epitope tag it further comprises an additional heterologous agent.
The conjugate of any proceeding claim, wherein the conjugate further comprises a moiety to increase in vivo stability or in vivo half life, or wherein the heterologous agent comprises a moiety to increase in vivo stability or in vivo half life.
The conjugate of any proceeding claim, wherein the heterologous agent is N-terminal to the peptide.
The conjugate of any proceeding claim, wherein the heterologous agent is C-terminal to the peptide.
The conjugate of any proceeding claim, wherein the conjugate further comprises an Fc portion of an antibody.
The conjugate of any proceeding claim, further comprising a linker interconnecting the A44/K39 peptide portion and the heterologous agent.
The conjugate of any proceeding claim, wherein (i) and (ii) are interconnected by a linker.
The conjugate of any proceeding claim, wherein the A44/K39 peptide portion and heterologous agent are directly interconnected without a linker.
The conjugate of any preceding claim, wherein the A44/K39 peptide portion comprises an amino acid sequence at least 80% identical to SEQ ID NO.:
- 1, or a fragment thereof capable of entering a cell by endocytosis and translocating to mitochondria.
The conjugate of any preceding claim, wherein the A44/K39 peptide portion comprises an amino acid sequence at least 80% identical to SEQ ID NO.:
- 2, or a fragment thereof capable of entering a cell by endocytosis and translocating to mitochondria.
The conjugate of any preceding claim, wherein the A44/K39 peptide portion comprises an amino acid sequence at least 80% identical to SEQ ID NO.:
- 3 or SEQ ID NO.:
- 4, or a fragment thereof capable of entering a cell by endocytosis and translocating to mitochondria.
The conjugate of any preceding claim, wherein the A44/K39 peptide portion comprises an amino acid sequence at least 80% identical to SEQ ID NO.:
- 5 or SEQ ID NO.:
- 6, or a fragment thereof capable of entering a cell by endocytosis and translocating to mitochondria.
The conjugate of any preceding claim, wherein the cell is an epithelial cell.
The conjugate of any proceeding claim, wherein the heterologous agent is a protein, peptide, polynucleotide, oligonucleotide or small organic molecule.
The conjugate of any preceding claim, wherein the conjugate comprises a fusion protein comprising the A44/K39 peptide portion and the heterologous agent.
The conjugate of any preceding claim, wherein the heterologous agent is a pharmaceutical agent.
The conjugate of any preceding claim, wherein the heterologous agent is a nutraceutical agent.
The conjugate of any preceding claim, wherein the heterologous agent is a therapeutic agent or a therapeutically active agent, such as an antioxidant.
The conjugate of any preceding claim, wherein the heterologous agent is endogenously present or active in mitochondria.
The conjugate of any preceding claim, wherein the heterologous agent is suitable for treating a mitochondrial disease or condition.
A composition comprising the conjugate of any preceding claim and one or more pharmaceutically acceptable carriers and/or excipients.
A nucleic acid construct, comprising a nucleotide sequence that encodes (i) the conjugate of any preceding claim or (ii) the peptide portion of the conjugate of any preceding claim, wherein the nucleic acid construct encodes a conjugate capable of entering a cell by endocytosis and localizing to mitochondria.
-86. (canceled)
Dependencies are inferred from the claim text.