Hybrid proteins that migrate retrogradely and transynaptically into the CNS

US7435792B2 · kind B2 · utility

Assignee

• INSTITUT PASTEUR · FR

Inventors

• Laurent Coen · Montreuil, FR
• Rosario Osta Pinzolas · Zaragoza, ES
• Philippe Brulet · Maurepas, FR

Key dates

• Filing date: Mar 26, 2001
• Grant date: Oct 14, 2008
• Expiry date: Aug 20, 2022

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2319/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The non-toxic proteolytic C fragment of tetanus toxin (TTC peptide) has the same ability to bind nerve cells and be retrogradely transported through a synapse as the native toxin. A hybrid protein encoded by the IacZ-TTC gene fusion retains the biological functions of both proteins in vivo, i.e. retrograde transynaptic transport of the TTC fragment and β-gal enzymatic activity. After intramuscular injection, enzymatic activity could be detected in motoneurons and connected neurons of the brainstem areas. This strategy is useful for the delivery of a biological activity to neurons from the periphery to the central nervous system. Such a hybrid protein can also be used to map synaptic connections between neural cells.