Topical compositions and uses

Abstract

The present disclosure provides chimeric polypeptides that include one or more zinc finger motif fused to a therapeutic peptide such as botulinum neurotoxins (BoNTs). The zinc finger motif may be located at the C-terminal side of the BoNT and the chimeric polypeptide can optionally include two or more such zinc finger motifs. It is shown that the disclosed chimeric polypeptides can be efficiently delivered to a subject transdermally.

1 . A chimeric polypeptide comprising (a) a botulinum toxin (BoNT) light chain, (b) a BoNT heavy chain, and (c) a cell penetration peptide located to the C-terminal of the BoNT light chain or located to the C-terminal to the BoNT heavy chain which is located C-terminal to the BoNT light chain or bound to the BoNT light chain through a disulfide bond. 
     
     
         2 . The chimeric polypeptide of  claim 1 , wherein the chimeric polypeptide does not include more than 2000 amino acid residues. 
     
     
         3 . The chimeric polypeptide of  claim 1 , wherein the BoNT light chain and the cell penetration peptide are on the same peptide chain. 
     
     
         4 . The chimeric polypeptide of  claim 1 , wherein the BoNT light chain and the cell penetration peptide are on different peptide chains. 
     
     
         5 . The chimeric polypeptide of  claim 1 , wherein the cell penetration peptide is the transactivator of transcription peptide (TAT). 
     
     
         6 . The chimeric polypeptide of  claim 1 , wherein the cell penetration peptide is the pep-1 peptide (Pep-1). 
     
     
         7 . The chimeric polypeptide of  claim 1 , wherein the cell penetration peptide is not longer than 200 amino acid residues away from the C-terminus of the BoNT light chain or the BoNT heavy chain. 
     
     
         8 . The chimeric polypeptide of  claim 1 , wherein the BoNT is selected from BoNT A, B, C, D, E, F, or G or variants having at least 90% sequence identity thereto. 
     
     
         9 . The chimeric polypeptide of  claim 8 , wherein the BoNT is selected from subtypes of BoNT A1-A10, B1-B8, E1-E9, and F1-F7. 
     
     
         10 . The chimeric polypeptide of  claim 8 , wherein the BoNT is BoNT A. 
     
     
         11 . The polypeptide of  claim 1 , wherein the BoNT light chain comprises the amino acid sequence of SEQ ID NO: 8 or an amino sequence having at least 90% sequence identity to SEQ ID NO: 8. 
     
     
         12 . The polypeptide of  claim 1 , wherein the BoNT heavy chain comprises the amino acid sequence of SEQ ID NO: 9 or an amino sequence having at least 90% sequence identity to SEQ ID NO: 9. 
     
     
         13 . The polypeptide of  claim 1 , comprising a single-chain polypeptide comprising the amino acid sequence of SEQ ID NO: 16. 
     
     
         14 . The polypeptide of  claim 1 , comprising a single-chain polypeptide comprising the amino acid sequence of SEQ ID NO: 17. 
     
     
         15 . A method for treating a condition in a subject in need thereof, comprising topical or intramuscular administration of the chimeric polypeptide of  claim 1 . 
     
     
         16 . The method of  claim 15 , wherein the topical use is on a skin or a mucous membrane of an eye, ear, nose, mouth, lip, urethral opening, anus, or tongue. 
     
     
         17 . The method of  claim 15 , wherein the topical use is on a stratum corneum of a skin that has been disrupted. 
     
     
         18 . The method of  claim 17 , wherein the disruption is carried out with a needle or microneedle used for delivering the formulation. 
     
     
         19 . The method of  claim 15 , wherein the condition is facial wrinkle, dystonias, sparsticity, hemifacial spasm, hyperhidrosis, or hypersalivation. 
     
     
         20 . A polynucleotide encoding a chimeric polypeptide of  claim 1 .