University of SzegedOpportunity Contact
Enikő Koppány, Business Development Manager
Szeged, Hungary

University of Szeged Website
TherapeuticEarly Stage

The WYKYW pentapeptide is an endocytosis routing sequence for cell delivery of therapeutic macromolecules at therapeutically relevant nanomolar concentrations and avoids lysosomal degradation. This short peptide tag is able to route its cargo to an entry pathway that mimics the internalization of viruses and bacterial toxins.

Cardiovascular diseases including sudden cardiac death and stroke are among the leading causes of mortality in industrialized countries. At present the pharmacological treatment of arrhythmias including atrial fibrillation is not satisfactory since the available drugs either do not control arrhythmias properly or induce serious side effects, Therefore, there is an increasing demand for safe and effective new drugs to treat atrial fibrillation and arrhythmias. Chronic AMIO application is the most effective pharmacological treatment to combat atrial fibrillation and arrhythmias with less proarrhythmic risk than other currently used antiarrhythmics. However, AMIO – which has a very complex model of action inhibiting cardiac sodium, calcium, potassium currents, and beta-adrenoceptors – also exerts serious extracardiac adverse effects which generally limit its clinical use.

Description of Technology
There is a pressing need to develop ways to deliver therapeutic macromolecules to their intracellular targets. The mammalian cell membrane is a major obstacle in drug development because it represents a barrier that is mostly impermeable to extracellular proteins that can potentially act as specific, efficient, and tolerable drugs. Certain viral and bacterial proteins are readily internalized in a functional form through lipid raft-mediated/caveolar endocytosis, but mimicking this process with protein cargoes at therapeutically relevant concentrations is a great challenge. The present invention offers new methods for intracellular delivery. Targeting ganglioside GM1 in the caveolar pits triggers endocytosis. A minimal palindromic pentapeptide sequence (WYKYW) specifically binds the carbohydrate moiety of GM1 with low nanomolar affinity. Direct attachment of this short endocytosis routing tag to large proteins facilitate lipid raft-mediated/caveolar endocytosis of the macromolecules at therapeutically relevant nanomolar concentrations and avoid endosomal entrapment and lysosomal degradation; the cargo-loaded caveosomes do not fuse with lysosomes. Specific and high-affinity targeting of ganglioside GM1 is especially sought because GM1 is expressed in many mammalian cell types, including endothelial cells, and is overexpressed in cancer cells.


  • the pentapeptide specifically triggers the caveolar/lipid raft-mediated endocytotic process at low nanomolar concentrations
  • carrier for cargos from small molecules up to associates of macromolecules.
  • delivering therapeutic or diagnostic molecules, biomolecules, macromolecules to the site of action in the cells
  • selectivity for cell types that overexpress GM1, a characteristic of many tumor cells.

Clinical Trials
There are no available clinical trials yet. A structurally intact immunoglobulin G complex (580 kDa) is successfully delivered into live HeLa cells at extracellular concentrations ranging from 20 to 160 nm, and escape of the cargo proteins to the cytosol was observed.

Type of Business Relationship Sought
Out license, Partnership

Patent Information
Hungarian application

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