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.

Research Tool for Protein Conformation Analysis

UW–Madison researchers have developed a method and easy-to-operate device that uses plasma to perform hydroxyl radical footprinting. The device tags the outer surface of the protein and allows the user to study its 3-D conformation via mass spectrometry.

The new technique, which is workable on a benchtop, applicable to a range of protein concentrations and sizes and generates µs bursts of hydroxyl radicals without added chemicals or reagents, has been developed and the results benchmarked. It is useful for quickly performing epitope mapping or assessing protein structural characteristics such as unfolding and conformational changes. The method can be used with two or more distinct proteins to map binding events, which enables pharmaceutical and R&D labs to image proteins in their natural state.

The researchers believe this tool will enable much quicker turnaround (on the order of hours) than X-ray crystallography and more reliable data than Hydrogen-Deuterium Exchange (HDX). It can be manufactured alone or in conjunction with mass spectrometry systems.

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.

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

Enhancing Cell Penetration to Improve Drug Delivery

UW–Madison researchers have developed a method for enhancing cellular uptake of a cargo molecule by covalently bonding fluorenyl groups to it. The fluorenylated molecule is then contacted with the cell or tissue. Cellular uptake may be in vivo or in vitro and includes at least partial penetration into the cytosol.

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.

Enhanced Drug Delivery Across the Blood-Brain Barrier: pH-Dependent Antibodies Targeting the Transferrin Receptor

UW–Madison researchers have developed several new single-chain antibody fragments to the transferrin receptor which exhibit increased dissociation at pH 5.5. Such targeting antibodies could have immense potential for drug delivery into and across target cells including cancer cells and the BBB.

Unlike other anti-TfR antibodies in development for cancer or brain delivery, the new antibodies have been endowed with pH-sensitivity resulting in differential trafficking and increased intracellular accumulation up to 2.6 times their wild-type parent.