Chimeric receptor binding proteins resistant to proteolytic degradation
AssigneeEligo Bioscience
InventorsJesus Fernandez Rodriguez, Xavier Duportet
Life of this patent
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Abstract
The present disclosure provides a chimeric receptor binding protein (RBP) resistant to proteolytic digestion wherein said RBP comprises a portion of a receptor binding protein derived from a bacteriophage fused through a designed linker region consisting of 1 to 70 amino acids, to a portion of a receptor binding protein derived from a different bacteriophage, wherein said linker region is designed to be resistant to proteolytic digestion.
Claims25
A lambdoid bacterial delivery vehicle comprising a chimeric receptor binding protein (RBP) resistant to proteolytic digestion,
- wherein said chimeric RBP comprises an N-terminal region of a side tail fiber (STF) protein from a lambdoid bacteriophage, fused through a designed linker region consisting of 1 to 70 amino acids or 1 to 30 amino acids, to a C-terminal region of a RBP protein from a different bacteriophage, wherein said N-terminal region and C-terminal region are fused within an insertion site of the N-terminal STF region, said insertion site having at least 80% identity with a site selected from the group consisting of amino acids SAGDAS (SEQ ID NO:
- 1), ADAKKS (SEQ ID NO:
- 2), MDETNR (SEQ ID NO:
- 3), SASAAA (SEQ ID NO:
- 4) and GAGENS (SEQ ID NO:
- 5);
- and
- wherein said designed linker region comprises a helix or helical bundle and wherein said linker region is resistant to proteolytic cleavage.
A pharmaceutical or veterinary composition comprising:
- a lambdoid bacterial delivery vehicle comprising a chimeric receptor binding protein (RBP) resistant to proteolytic digestion,
- wherein said chimeric RBP comprises an N-terminal region of a side tail fiber (STF) protein from a lambdoid bacteriophage, fused through a designed linker region consisting of 1 to 70 amino acids or 1 to 30 amino acids, to a C-terminal region of a RBP protein from a different bacteriophage, wherein said N-terminal region and C-terminal region are fused within an insertion site of the N-terminal STF region, said insertion site having at least 80% identity with a site selected from the group consisting of amino acids SAGDAS (SEQ ID NO:
- 1), ADAKKS (SEQ ID NO:
- 2), MDETNR (SEQ ID NO:
- 3), SASAAA (SEQ ID NO:
- 4) and GAGENS (SEQ ID NO:
- 5);
- and
- wherein said designed linker region comprises a helix or helical bundle and
- wherein said linker region is resistant to proteolytic cleavage;
- and
- a pharmaceutically acceptable carrier.
A method for in vivo delivery of a DNA payload of interest into a subject comprising administering to said subject a pharmaceutical or veterinary composition comprising:
- a lambdoid bacterial delivery vehicle for use in in vivo delivery of a DNA payload of interest into a targeted bacterial cell, wherein said lambdoid delivery vehicle comprises a chimeric receptor binding protein (RBP) resistant to proteolytic digestion,
- wherein said chimeric RBP comprises an N-terminal region of a side tail fiber (STF) protein from a lambdoid bacteriophage, fused through a designed linker region consisting of 1 to 70 amino acids or 1 to 30 amino acids, to a C-terminal region of a RBP protein from a different bacteriophage, wherein said N-terminal region and C-terminal region are fused within an insertion site of the N-terminal STF region, said insertion site having at least 80% identity with a site selected from the group consisting of amino acids SAGDAS (SEQ ID NO:
- 1), ADAKKS (SEQ ID NO:
- 2), MDETNR (SEQ ID NO:
- 3), SASAAA (SEQ ID NO:
- 4) and GAGENS (SEQ ID NO:
- 5);
- and
- wherein said designed linker region comprises a helix or helical bundle and
- wherein said linker region is resistant to proteolytic cleavage;
- and
- a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.