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 recombinant Staphylococcus epidermidis bacterium capable of secreting a filaggrin (FLG) polypeptide, wherein the recombinant Staphylococcus epidermidis bacterium comprises an expression vector comprising a first coding sequence comprising a gene capable of expressing the filaggrin polypeptide, wherein the filaggrin polypeptide consists of: SEQ ID NO: 46 and a second coding sequence comprising a gene capable of expressing a cell penetrating peptide.
2. The recombinant Staphylococcus epidermidis bacterium of claim 1 , further comprising a third coding sequence comprising a gene capable of expressing an export signal.
3. The recombinant Staphylococcus epidermidis bacterium of claim 1 , wherein the Staphylococcus epidermidis bacterium secretes a filaggrin fusion protein.
4. A biotherapeutic composition comprising a live recombinant Staphylococcus epidermidis bacterium wherein the recombinant Staphylococcus epidermidis bacterium comprises
(i) a first coding sequence comprising a nucleic acid sequence capable of expressing a therapeutic polypeptide, wherein the therapeutic polypeptide consists of SEQ ID NO: 46;
(ii) a second coding sequence comprising a nucleic acid sequence capable of expressing a cell penetrating peptide;
(iii) a third coding sequence comprising a nucleic acid sequence capable of expressing 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 are capable of expressing a filaggrin fusion product.
5. The composition of claim 4 , wherein the export signal exports the filaggrin fusion product out of the recombinant bacterium.
6. The composition of claim 4 , wherein the cell penetrating peptide facilitates the entry of the filaggrin fusion product into a human keratinocyte.