Pharmaceuticals & Vitamin D
Cytotoxic Ribonuclease Variants
Inventors: Ronald Raines, Julie Mitchell, Thomas Rutkoski
The Wisconsin Alumni Research Foundation (WARF) is seeking commercial partners interested in developing new, highly cytotoxic variants of the bovine ribonuclease A (RNase A) superfamily of ribonucleases.
Ribonucleases are enzymes that catalyze the degradation of RNA. Levels of RNase activity are controlled in vivo by a ribonuclease inhibitor (RI), which binds strongly to an RNase to completely inhibit its catalytic activity. An RNase can be made cytotoxic by modifying its amino acid sequence so RI can’t bind to it.
UW-Madison researchers have developed new, highly cytotoxic variants of the bovine ribonuclease A (RNase A) superfamily of ribonucleases. They used the Fast Atomic Density Evaluation (FADE) algorithm for molecular interaction analysis to model the locations where RNase A and RI are in molecular contact. The amino acid sequence of RNase A was then modified at these locations so it could not be easily bound by RI. The modified ribonucleases retain their catalytic properties and are more cytotoxic than previously engineered ribonucleases.
- Cancer treatment
- More toxic to cancer cells than other known ribonucleases
- Likely to exhibit a more favorable therapeutic index (ratio of toxic to effective dose) than a current cancer therapeutic based on a frog homolog of RNase A