Recombinant filaggrin polypeptides for cell importation

Abstract

Disclosed are recombinant polypeptides that include (a) a filaggrin amino acid sequence and (b) a cell importation signal sequence that includes a motif of two to fifteen amino acids, wherein the motif includes at least one arginine residue and at least one methionine residue. Also disclosed are nucleic acids encoding the recombinant polypeptides of the present invention, and compositions that include the recombinant polypeptides and nucleic acids of the present invention. Methods of treating or preventing a skin disease or skin disorder using the compositions of the present invention are also included, as well as kits that include a sealed containing that includes a recombinant polypeptide of the present invention.

1 . A recombinant polypeptide comprising a human filaggrin sequence and a cell importation sequence positioned on the N-terminus side or the C-terminus side of the filaggrin sequence. 
     
     
         2 . The recombinant polypeptide of  claim 1 , further comprising a linker region positioned between the human filaggrin sequence and the cell importation sequence. 
     
     
         3 . The recombinant polypeptide of  claim 1 , wherein the cell importation sequence comprises an RMR tag. 
     
     
         4 . The recombinant polypeptide of  claim 3 , wherein the RMR tag comprises SEQ ID NO:23. 
     
     
         5 . The recombinant polypeptide of  claim 3 , wherein the RMR tag consists of SEQ ID NO:23. 
     
     
         6 . The recombinant polypeptide of  claim 3 , wherein the cell importation sequence is positioned on the C-terminus side of the filaggrin sequence. 
     
     
         7 . The recombinant polypeptide of  claim 1 , comprised in a topical formulation. 
     
     
         8 . The recombinant polypeptide of  claim 7 , wherein the topical formulation is an emulsion, a cream, a lotion, a gel, or an ointment. 
     
     
         9 . A recombinant polypeptide comprising a human filaggrin sequence and an RMR sequence motif positioned on the N terminus side or the C-terminus side of the filaggrin sequence. 
     
     
         10 . The recombinant polypeptide of  claim 9 , wherein the motif comprises repeating units of RMR. 
     
     
         11 . The recombinant polypeptide of  claim 10 , wherein the RMR sequence motif comprises SEQ ID NO:23. 
     
     
         12 . The recombinant polypeptide of  claim 11 , wherein the RMR sequence motif consists of SEQ ID NO:23. 
     
     
         13 . The recombinant polypeptide of  claim 10 , wherein the RMR sequence motif is positioned on the C-terminus side of the filaggrin sequence. 
     
     
         14 . The recombinant polypeptide of  claim 9 , further comprising a linker region positioned between the human filaggrin sequence and the RMR sequence motif. 
     
     
         15 . The recombinant polypeptide of  claim 9 , comprised in a topical formulation. 
     
     
         16 . The recombinant polypeptide of  claim 15 , wherein the topical formulation is an emulsion, a cream, a lotion, a gel, or an ointment. 
     
     
         17 . A recombinant chimeric nucleic acid molecule comprising a human filaggrin coding region under the control of a eukaryotic or prokaryotic promoter. 
     
     
         18 . The recombinant nucleic acid molecule of  claim 17 , wherein the promoter is a eukaryotic promoter. 
     
     
         19 . The recombinant nucleic acid molecule of  claim 17 , wherein the promoter is a prokaryotic promoter. 
     
     
         20 . The recombinant nucleic acid molecule of  claim 17 , further defined as an expression vector. 
     
     
         21 . The recombinant nucleic acid molecule of  claim 20 , wherein the expression vector is a prokaryotic expression vector. 
     
     
         22 . The recombinant nucleic acid molecule of  claim 20 , wherein the expression vector is a eukaryotic expression vector. 
     
     
         23 . The recombinant nucleic acid molecule of  claim 17 , wherein the molecule further comprises a region encoding a cell importation sequence. 
     
     
         24 . The recombinant chimeric nucleic acid molecule of  claim 17 , wherein the molecule further comprises a region encoding an RMR tag. 
     
     
         25 . The recombinant polypeptide of  claim 24 , wherein the RMR tag comprises SEQ ID NO:23. 
     
     
         26 . The recombinant polypeptide of  claim 26 , wherein the RMR tag consists of SEQ ID NO:23. 
     
     
         27 . The recombinant nucleic acid molecule of  claim 17 , further comprising a region encoding a linker region positioned between the human filaggrin sequence and the cell importation sequence. 
     
     
         28 . The recombinant chimeric nucleic acid molecule of  claim 17 , positioned in a host cell that expresses human filaggrin. 
     
     
         29 . The recombinant chimeric nucleic acid molecule of  claim 28 , wherein the host cell is a prokaryote. 
     
     
         30 . The recombinant chimeric nucleic acid molecule of  claim 29 , wherein the host cell is a bacteria. 
     
     
         31 . The recombinant chimeric nucleic acid molecule of  claim 28 , wherein the host cell is a eukaryote. .