The present invention relates to a method for identifying a gene that modulates Clostridial neurotoxin activity, comprising the steps of: a. providing a sample of human neuronal cells expressing a polypeptide comprising a C-terminal detectable label, wherein the polypeptide is cleavable by Clostridial neurotoxin; b. altering the expression of the target gene in the cell; c. contacting the cell with Clostridium neurotoxin; d. measuring the amount of the C-terminal detectable label, thereby quantifying Clostridial neurotoxin activity; and e. when the quantified Clostridial neurotoxin activity is different from the quantified Clostridial neurotoxin activity when the expression of the target gene is unaltered, identifying the target gene as a modulator of Clostridial neurotoxin activity; or f. When the quantified Clostridial neurotoxin activity is equivalent to the quantified Clostridial neurotoxin activity when the expression of the target gene is unaltered, confirming that the target gene is not a modulator of Clostridial neurotoxin activity. Also provided are related methods for identifying agents that modulate Clostridial neurotoxin activity, as well as human neuronal cells, nucleotides, vectors, polypeptides, kits, and compositions suitable for use in the methods of the present invention.
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