Recombinant derivatives of clostridial neurotoxins as delivery vehicles for proteins and small organic molecules

Clostridial neurotoxins are the most powerful toxins known. Nevertheless, d erivatives of these toxins may find broad applications both in science and medicine because of their unique abilities to recognize neurons and deliver small and large molecules into them. In this paper we describe the constru ction of two types of such derivatives. Proteins belonging to the first cla ss were designed to allow direct conjugation with one or few molecules of i nterest. Proteins belonging to the second class contain biotin residue and therefore could be easily connected to streptavidin loaded with multiple mo lecules of interest. Only C-terminal regions of neurotoxin heavy chains wer e incorporated in the structure of recombinant proteins. Nevertheless, reco mbinant proteins were found to be able to recognize specific neuronal recep tors and target model molecules to rat synaptosomes and human neuroblastoma cells.