Expression of the human lekti gene from the chromosome of Staphylococcus epidermidis
AssigneeAzitra Inc
InventorsTrudy H. Grossman, Alexander Tikhonov
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Abstract
The present disclosure provides, inter alia, engineered microbes expressing one or more therapeutic proteins from a nucleotide sequence chromosomally integrated, which is effective to treat or ameliorate a disease or disorder, e.g., a skin disease. In certain embodiments, composition, methods, and kits are provided comprising microbes expressing one or more therapeutic proteins from a chromosomally integrated nucleotide sequence.
Claims15
A recombinant microorganism capable of secreting one or more therapeutic polypeptides, wherein the recombinant microorganism is selected from the group consisting of Moraxella, Corynebacteria, Pasteurella, Haemophilus, Streptococcus, and Staphylococcus, and wherein the recombinant microorganism comprises
- (i) a first coding sequence comprising a nucleic acid sequence encoding the one or more therapeutic polypeptides, wherein the one or more therapeutic polypeptides comprise LEKTI domain 6 (D6);
- (ii) a second coding sequence comprising a nucleic acid sequence encoding one or more secretion peptides that are not associated with the one or more therapeutic polypeptide in nature;
- and
- (iii) a third coding sequence comprising a nucleic acid sequence encoding a pro-peptide, wherein the nucleic acid sequence encoding the pro-peptide is set forth in SEQ ID NO:
- 123,
- wherein the first coding sequence, the second coding sequence, and the third coding sequence are linked to a promoter and wherein the first coding sequence, the second coding sequence, and the third coding sequence are chromosomally integrated into a hld gene.
A live biotherapeutic composition comprising a recombinant microorganism, wherein the recombinant microorganism is selected from the group consisting of Moraxella, Corynebacteria, Pasteurella, Haemophilus, Streptococcus, or Staphylococcus, wherein the recombinant microorganism comprises:
- a nucleic acid sequence comprising one or more nucleic acid sequences encoding (i) LEKTI protein domain 6 (D6), (ii) one or more secretion peptides, (iii) a pro-peptide comprising SEQ ID No:
- 123, and (iv) a promoter, wherein the nucleic acid sequence is integrated into the hld gene in the chromosome of the cell, and
- wherein the recombinant microorganism is capable of secreting the LEKTI protein domain 6 (D6).
Dependencies are inferred from the claim text.