Drug Discovery

Most Recent Inventions

Genetic Testing for Acquired Peripheral Neuropathy in Dogs

UW–Madison researchers have identified a single nucleotide polymorphism (SNP) that is predictive of APN syndrome in dogs, based on a genome-wide association study. Using a population of Labrador retrievers (56 cases and 26 controls), the researchers have shown that a SNP on CFA1 tags the causal variant for APN in the Labrador retriever breed.

Rhinovirus-C Peptide for Development of Vaccines and Antivirals

UW–Madison researchers have identified novel immunogenic peptides from RV-C that are useful targets for therapeutic antibodies.

Recent advances in microscopy enabled the researchers to determine (with atomic resolution) the structure of an RV-C strain, both in its full, infectious form and as native empty particles. The structures highlighted immunogenic surfaces that could be used to design antivirals or vaccines against RV-C.

Enhanced Endotoxin Detection: New Advantages in Liquid Crystal Assays for Gram-Negative Pathogens

UW–Madison researchers have now demonstrated enhanced endotoxin detection in the presence of masking agents in their previous liquid crystal system.

Unlike the LAL assay, the LC-based method does not suffer from LER or any loss of sensitivity due to the presence of cations (e.g., Ca2+ or Mg2+), buffers (e.g., citrate), surfactants (e.g., SDS), chelating agents (e.g., EDTA), proteins or nucleic acids (e.g., DNA or RNA). Thus, the LC-based method provides faster and cheaper detection of endotoxin when compared to existing methods, such as the LAL assay.

Adapted Rhinovirus C for Maximum Virus Yield

Building on their work, the researchers have now developed a mutated RV-C strain that induces strong cytopathic effect and replicates vigorously in the HeLa-E8 cells, yielding more than a log higher level of infectious rhinovirus particles compared to the parental clinical isolate.

New System for Producing Fungal Secondary Metabolites

UW–Madison researchers have developed a new system for producing fungal secondary metabolites using test plasmids and a genetically modified strain of Aspergillus nidulans (TPMW2.3). The strain begins producing secondary metabolites when a gene promoter in the plasmid is triggered by culture conditions. This allows researchers to induce or repress production.

Most Recent Patents

Yeast-Based Intein Platform for Drug Production

UW–Madison researchers have engineered non-self-cleaving Mxe GyrA inteins shown to significantly improve the production of fusion proteins from Saccharomyces cerevisiae. The novel inteins were developed through directed evolution, and they enhance fusion protein display (up to 3x) and secretion levels (up to 30x) compared to the wild type intein. The new yeast-based platform provides a robust alternative to bacterial intein expression systems.

Bioreversible Boronates Improve Drug Delivery

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.

Blood-Brain Barrier Targeting Antibodies to Improve Drug Delivery

UW–Madison researchers have identified a pair of single-chain antibody fragments (scFv15 and scFv38) that may help drugs cross the BBB. The two promising new antibodies are capable of binding antigens expressed at the BBB in vivo.

The researchers panned a human scFv library to identify candidates that specifically bind to brain endothelial cell receptors and may pass through the BBB. Drugs or drug carriers could be attached to these fragments and then transported into the brain.