Methods and compositions for treating inflammatory skin disease with recombinant microorganisms
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Publication Number
US-12208124-B2
Publication Date
2025-01-28
Expiration Date
Abstract
The present invention provides isolated plasmids, recombinant microorganisms, kits, and methods for the treatment of inflammatory skin disease.
Core Innovation
The disclosed invention provides an engineered, skin-colonizing recombinant Staphylococcus epidermidis bacterium capable of secreting a filaggrin (FLG) polypeptide for treating inflammatory skin diseases. The recombinant bacterium comprises an expression vector including a first coding sequence capable of expressing a filaggrin polypeptide consisting of SEQ ID NO: 46, together with a second coding sequence capable of expressing a cell penetrating peptide.
The disclosure further provides an export signal coding sequence and a promoter operably linked to the coding sequences. The filaggrin polypeptide is configured as a filaggrin fusion product, and the export signal supports secretion or export of the filaggrin fusion product.
The biotherapeutic composition comprises a live recombinant Staphylococcus epidermidis bacterium in which the promoter, filaggrin coding sequence, cell penetrating peptide coding sequence, and export signal coding sequence are capable of expressing the filaggrin fusion product. The cell penetrating peptide facilitates entry into a human keratinocyte.
Claims Coverage
The provided independent claims cover two related aspects: a recombinant Staphylococcus epidermidis bacterium with secretion of an FLG polypeptide configured with a cell penetrating peptide, and a live biotherapeutic composition using the same engineered bacterium including an export signal and a promoter driving expression of a filaggrin fusion product. Across the independent claims, there are three main inventive elements: engineered secretion of filaggrin expression, incorporation of a cell penetrating peptide, and inclusion of an export signal under promoter control.
Recombinant Staphylococcus epidermidis secreting SEQ ID NO: 46 filaggrin with a cell penetrating peptide
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.
Live biotherapeutic composition using recombinant Staphylococcus epidermidis expressing a filaggrin fusion product with export signal and promoter control
A biotherapeutic composition comprising a live recombinant Staphylococcus epidermidis bacterium wherein the recombinant Staphylococcus epidermidis bacterium comprises a first coding sequence capable of expressing a therapeutic polypeptide consisting of SEQ ID NO: 46, a second coding sequence capable of expressing a cell penetrating peptide, a third coding sequence capable of expressing an export signal, and 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.
Overall, the claim set ties secretion of an FLG polypeptide consisting of SEQ ID NO: 46 to expression of a cell penetrating peptide, and further specifies that a promoter-controlled construct includes an export signal to express a filaggrin fusion product. The dependent claim refinements specify exporting the filaggrin fusion product out of the recombinant bacterium and facilitating entry into a human keratinocyte.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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