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 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.

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.

Most Recent Patents

New Viral Propagation Method Yields Insight Into Childhood Asthma

UW–Madison researchers have developed an efficient, cost-effective method of propagating RV-C. They discovered that human cadherin-related family member 3 (CDHR3) is the receptor for RV-C and allows cell lines normally unsusceptible to HRV-C infection to support virus binding and replication.

To create cell lines capable of efficiently growing RV-C, the researchers modify the host cell so it expresses an effective amount of the CDHR3 receptor. This method enables high-throughput, large-scale production of RV-C, which in turn enables critical basic and applied research regarding this understudied pathogen.

Improved Method to Produce Brain Microvascular Endothelial Cells for a Robust Human Blood-Brain Barrier Model

UW–Madison researchers have devised a novel method for reproducibly and efficiently growing human BMECs from human pluripotent stem cells (hPSCs), which include both induced pluripotent stem cells (IPSCs) and embryonic stem cells (ESCs). The BMECs have characteristic BBB properties, such as the expression of well-organized tight junctions and high transendothelial resistance. They can be used to create high-fidelity in vitro human BBB models.

The hPSCs are grown on a suitable matrix, such as Matrigel-coated plates, and subjected to an unconditioned medium. After several days, endothelial cell medium is added. Finally, other signals needed for further maturation of the BMECs are provided, and the cells are tested for BBB properties. Flow cytometry may be used to quantify cell development.

Reagents for Bioreversible Protein Esterification

UW–Madison researchers have developed an optimized diazo compound, derived from phenylglycine amide, for converting carboxylate groups into an ester in high yield in buffered water. The ensuing esters are labile to esterase enzymes such as reside in all human cells, making the modification bioreversible. The novel compound is small, avoids deleterious side reactions and has a modularity that enables broad utility.