WARF: P150009US02

Bioreversible Boronates Improve Drug Delivery


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.
OVERVIEWThe 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 INVENTIONA 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.
BUSINESS OPPORTUNITYThis invention provides a new means of delivering molecules into mammalian cells. Presently, the most common method in use is LipofectamineTM (Invitrogen Inc.), which has annual sales near half a billion dollars. However, Lipofectamine can only be used in vitro and not to deliver drugs. Also, this reagent is retained in the cell membrane. The new approach has neither of these limitations.
  • Boronate-mediated delivery of drugs, proteins, nucleic acids and other molecules
  • Bioreversible
  • Demonstrated to enhance cellular uptake
  • Delivery can take place in vivo or in vitro.
STAGE OF DEVELOPMENTThe method has been exemplified using GFP, an anionic protein that has no tendency to enter mammalian cells.
For More Information About the Inventors
  • 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.
Contact Information
For current licensing status, please contact Jennifer Gottwald at or 608-960-9854.
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