Methods and compositions for treating inflammatory skin disease with recombinant microorganisms
The present invention provides isolated plasmids, recombinant microorganisms, kits, and methods for the treatment of inflammatory skin disease.
1 . A method of treating an inflammatory skin disease comprising administering to a mammalian subject in need thereof a therapeutically effective amount of a biotherapeutic composition comprising live recombinant Staphylococcus epidermidis comprising an expression vector, wherein the expression vector, or combination of bacteria, wherein the Staphylococcus epidermidis comprises
(i) a first coding sequence comprising a nucleic acid sequence encoding a filaggrin (FLG) therapeutic polypeptide, wherein the therapeutic polypeptide consists of SEQ ID NO: 46;
(ii) a second coding sequence comprising a nucleic acid sequence encoding a cell penetrating peptide;
(iii) a third coding sequence comprising a nucleic acid sequence encoding an export signal; and
(iv) a promoter operably linked to the first coding sequence, the second coding sequence and the third coding sequence, wherein the first coding sequence, the second coding sequence and the third-coding sequence,
wherein the recombinant Staphylococcus epidermidis first coding sequence, the second coding sequence and the third-coding sequence are capable of expresses a filaggrin fusion product comprising the FLG therapeutic polypeptide.
2 . The method of claim 1 , wherein the skin disease is atopic dermatitis.
3 . The method of claim 1 , wherein the composition is applied topically.
4 . The method of claim 1 , wherein the export signal exports the filaggrin fusion product out of the recombinant bacterium.
5 . The method of claim 1 , wherein the cell penetrating peptide facilitates the entry of the filaggrin fusion product into a human keratinocyte.
6 . The method of claim 1 , wherein the first coding sequence, the second coding sequence and the third coding sequences are arranged in a single plasmid.