Wisconsin Alumni Research Foundation

Drug Delivery
Drug Delivery
Bioreversible Boronates Improve Drug Delivery
WARF: P150009US02

Inventors: Ronald Raines, Thomas Smith

The Wisconsin Alumni Research Foundation (WARF) is seeking commercial partners interested in developing improved methods of boronating cargo molecules to enhance their uptake in cells.
The utility of many biologic drugs is limited by inefficient delivery into cells. Strategies to overcome this limitation have included enhancing the attraction between positively charged drug agents and the negatively charged cell surface. Other efforts have focused on natural ligands to target and bind agents to specific receptors on the cell surface.

Such methods have been used to deliver pharmaceuticals, proteins, peptides, nucleic acids and other particles into cells. While this has yielded some success, there remains a need for additional delivery strategies. In particular, the ability to bioreversibly modify molecules (i.e., enhance cellular uptake without effecting stability, function or immunogenicity) is highly desirable.
The Invention
A UW–Madison researcher has developed methods and reagents for enhancing cellular uptake in vivo or in vitro by attaching to any desired molecule one or more phenylboronic acid groups. The method is bioreversible; the boronate compound is cleaved from the molecule by intracellular enzymes, leaving its ‘cargo’ unaltered.

Advantageously, boronic acids readily form esters within the dense forest of polysaccharides, known as the glycocalyx, found on the surface of many cells. Targeting therapeutic agents to the glycocalyx has been shown to enhance cellular delivery. In addition, boronate groups are compatible with human physiology, appearing in chemotherapeutic agents and other remedies.
  • Boronate-mediated delivery of drugs, proteins, nucleic acids and other molecules
Key Benefits
  • Bioreversible
  • Demonstrated to enhance cellular uptake
  • Delivery can take place in vivo or in vitro.
Stage of Development
The method has been exemplified using GFP, an anionic protein that has no tendency to enter mammalian cells.
Additional Information
  • Andersen K.A., Smith T.P. and Raines R.T. 2016. Boronic Acid for the Traceless Delivery of Proteins into Cells. ACS Chem. Biol. 11, 319-323.
For current licensing status, please contact Jennifer Gottwald at [javascript protected email address] or 608-960-9854