Genetically modified probiotics for oral delivery of renin-angiotensin related therapeutic proteins and peptides

A method of treating a disease or condition involving the renin-angiotensin system (RAS), the method comprising administering orally to a subject in need thereof a therapeutically effective dose of a probiotic composition comprising either genetically modified bacteria expressing Ang-(1-7) or genetically modified bacteria expressing ACE2, or both,

• wherein the genetically modified bacteria expressing Ang-(1-7) and/or ACE2 comprises an expression vector comprising a polynucleic acid for expressing Ang-(1-7) and/or ACE2, wherein the polynucleic acid comprises:
• a promoter,
• a nucleic acid encoding a secretion signal peptide,
• a nucleic acid encoding a carrier protein, wherein the nucleic acid encoding the carrier protein has:
• (i) a polynucleic acid sequence having at least 80% sequence identity to SEQ ID NO:
• 3 or
• (ii) a polynucleic acid sequence having at least 95% sequence identity to SEQ ID NO:
• 18;
• a nucleic acid encoding Ang-(1-7) and/or ACE2, and
• a nucleic acid encoding a cleavage site that lies in between the nucleic acids encoding the carrier protein and Ang-(1-7) and/or ACE2;
• wherein the nucleic acids encoding the secretion signal peptide, carrier protein, Ang-(1-7) and/or ACE2, and cleavage site encode a fusion protein and are operably linked to the promoter.