abstract |
1. A polynucleotide encoding a neurotoxin polypeptide having a reduced duration of the biological effect exerted on a subject, wherein said polypeptide contains at least one light chain degradation signal. A polynucleotide according to claim 1, wherein said biological effect causes muscle paralysis in a subject. The polynucleotide of claim 1, wherein said reduced duration is less than 4, 3, or 2 weeks. The polynucleotide according to claim 1, wherein said degradation signal is selected from the group consisting of: a) at least one internally or terminally inserted PEST motif; b) at least one internally or terminally introduced motivation for recognition by E3 ligase; c) N-terminal oligo-lysine residue; d) N-terminally bound ubiquitin; e) substitution of the N-terminal proline with a basic amino acid; f) substitution of surface amino acid residues with lysine; id) substitutions of the N-terminal proline with the basic amino acid in combination with substitutions of the amino acid residues located on the surface with lysine. 5. A polynucleotide according to any one of claims 1 to 4, wherein said light chain of a polypeptide is obtained by modification from a light chain encoded by a polynucleotide containing a nucleic acid sequence selected from the group consisting of: a) a nucleic acid sequence having a nucleotide sequence as shown by SEQ ID NO: 1, 3, 5, 7, 9, 11, 13 or 15; b) a nucleic acid sequence encoding a polypeptide having an amino acid sequence as shown by SEQ ID NO: 2, 4, 6, 8, 10, 12, 14 or 16; and c) a nucleic acid sequence at least 40% identical in |