Drug Discovery

Most Recent Inventions

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.

Photoreceptor Scaffold for In Vitro Modeling and Transplantation Therapy

Using state-of-the-art microfabrication techniques, UW–Madison researchers have developed microstructured scaffold systems that can guide the growth of photoreceptor cells and mimic polarized outer retinal tissue. The scaffolds also may be used for transplantation of organized photoreceptor tissue with or without RPE.

Transplantation of photoreceptor-seeded scaffolds may improve grafted cell retention, survival, integration and functional visual rescue as compared to simple bolus injections. By recapitulating in vivo outer retinal architecture, these uniquely fabricated scaffolds also can be used for in vitro developmental and disease studies as well as drug screening.

The microfabrication process for scaffold production is fully compatible with numerous biomaterials, including biodegradable and non-biodegradable materials, thus allowing the scaffolds to be tailored to both in vitro and in vivo applications. The scaffolds feature biocompatible support layers (e.g., PDMS film) patterned with an array of unique through-holes having a curvilinear cell receiver and cell guide channels. The structure enables photoreceptors to be grown in a polarized orientation that mimics their development in vivo.

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.