New Biochip Mimics Liver Metabolism, Helps Streamline Drug Discovery
A collaboration of scientists has developed a new type of biochip technology that mimics the metabolism of a human liver, which could eliminate the need to use liver cells from human cadavers for toxicity testing of drugs.
Researchers from the Rensselaer Polytechnic Institute, Samsung Electro-Mechanics, the University of California in Berkeley, and Solidus Biosciences worked to develop the new technology. The resulting biochip called Transfected Enzyme and Metabolism Chip, or TeamChip, mimicked a hepatocyte in a more reliable and less expensive way compared to the traditional method. TeamChip can also altered to mimic hepatocytes from an individual patient, potentially leading the way to a future with more personalized drug toxicity testing.
Toxicity testing, which is often completed late in the preclinical phase of drug discovery, aims to examine the efficacy and toxicity of a drug candidate drug. Metabolism-induced drug toxicity, which affects the liver, is often the reason compounds don’t make it past the drug discovery process. However, this testing often entails harvesting and using liver cells from human cadavers. This means that metabolic capacity and profile of hepatocytes often vary and results in the loss of predictive capacity of in vitro tests, says study leader, Jonathan S. Dordick, VP for research and the Howard P. Isermann Professor at Rensselaer.
Each TeamChip is designed to feature 532 individual assays made up of the liver cells. The researchers engineered liver cells to metabolize drugs and drug candidates in high throughput. These are printed as liquids on the chips and quickly converted into gelatinous 3-D structures capable of more accurate mimicry of the conditions in the human body. The chips are incubated for up to three days and then analyzed for cell viability. Cells that produce toxic drug metabolites result in lower cell viability.
“This technology is a good way to determine, very early on, both the efficacy and the potential toxicity of a drug candidate. Having this information as early in the process as possible enables pharma companies to focus their limited resources on pushing forward only the most promising candidates with good efficacy and low toxicity,” Professor Dordick said.
The research team’s findings were published in the journal Nature Communications.