Methods and compositions for treating skin disease with recombinant microorganisms
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Publication Number
US-11850267-B2
Publication Date
2023-12-26
Expiration Date
Abstract
The present invention provides isolated plasmids, recombinant microorganisms, kits, and methods for the treatment of inflammatory skin disease.
Core Innovation
The invention provides a recombinant microorganism capable of secreting a filaggrin polypeptide, wherein the recombinant microorganism is Staphylococcus epidermidis. The microorganism comprises an expression vector with a first coding sequence that expresses a filaggrin polypeptide and a second coding sequence that expresses a cell penetrating peptide. The filaggrin polypeptide comprises an amino acid sequence at least 98% identical to SEQ ID NO: 1.
The invention further provides live biotherapeutic compositions in which Staphylococcus epidermidis is engineered to express filaggrin and a cell penetrating peptide. In certain embodiments, the expression system includes an export signal expressed by a third coding sequence, and a promoter operably linked to the coding sequences. The construct is capable of expressing a filaggrin fusion product, or a variant thereof, and is configured as a secretion-based therapeutic delivery approach.
The document connects filaggrin and filaggrin breakdown products to ichthyosis vulgaris and atopic dermatitis pathophysiology, and describes live biotherapeutic delivery through skin colonization by the engineered microorganism. The disclosure also includes documented experimental work and analytical approaches for detecting filaggrin and breakdown products and for assessing colonization and localization in skin-relevant contexts, including studies using reconstituted human epidermis and skin defect models.
Claims Coverage
The document includes three independent claims, directed to a recombinant microorganism, a live biotherapeutic composition, and a method of producing the live biotherapeutic composition. Across the independent claims, a primary inventive structure is an engineered Staphylococcus epidermidis expression system that produces secreted filaggrin therapeutic polypeptides, together with a cell penetrating peptide and, optionally, an export signal.
Engineered Staphylococcus epidermidis secreting filaggrin with a cell penetrating peptide
A recombinant microorganism capable of secreting a filaggrin polypeptide, wherein the recombinant microorganism is Staphylococcus epidermidis, comprising an expression vector comprising a first coding sequence comprising a gene capable of expressing the filaggrin polypeptide and a second coding sequence comprising a gene capable of expressing a cell penetrating peptide, wherein the filaggrin polypeptide comprises an amino acid sequence at least 98% identical to SEQ ID NO: 1.
Live biotherapeutic composition encoding filaggrin, a cell penetrating peptide, and an export signal
A live biotherapeutic composition comprising a recombinant microorganism capable of secreting a filaggrin polypeptide, wherein the recombinant microorganism is Staphylococcus epidermidis, comprising a first coding sequence capable of expressing the filaggrin therapeutic polypeptide, 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 coding sequences; wherein the coding sequences are capable of expressing a filaggrin fusion product, or variant thereof.
Producing the live biotherapeutic composition using transfected Staphylococcus epidermidis
A method for producing a live biotherapeutic composition comprising transfecting a Staphylococcus epidermidis cell with an expression vector comprising a first coding sequence capable of expressing the filaggrin polypeptide and a second coding sequence capable of expressing a cell penetrating peptide, allowing the transfected cell to produce a therapeutic polypeptide fusion protein, and obtaining the live biotherapeutic composition.
Across the independent claims, the claimed scope centers on an engineered Staphylococcus epidermidis expression vector that enables secretion of a filaggrin therapeutic polypeptide having at least 98% amino acid identity to SEQ ID NO: 1, together with a cell penetrating peptide, and optionally an export signal under promoter control to express filaggrin fusion products or variants. The independent claims also cover a live biotherapeutic composition containing this engineered microorganism and a production method that transfects Staphylococcus epidermidis to generate and obtain the live biotherapeutic composition.
Stated Advantages
Live biotherapeutic delivery is described as enabling stable in situ protein secretion.
The disclosure positions the approach as a non-steroidal option.
The disclosure states potential effectiveness at low application frequency.
Documented Applications
Treating a skin disease by administering the composition to a subject in need thereof.
Treating atopic dermatitis using the composition.
Treating ichthyosis vulgaris (IV) using the composition.
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