Researchers in South Korea have developed a technology to select genes from animal models that more accurately mimic human diseases, helping to minimize the difference between animal and human disease models when verifying effectiveness of drug candidates. The team at Pohang University of Science and Technology (POSTECH) say the technology will enhance and streamline the drug development process.
“Using this technology, we can predict the success or failure of animal disease models before making them and help develop more effective new drugs by better understanding disease mechanisms,” says POSTECH Professor and coauthor Sanguk Kim.
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Clinical trials verify the efficacy and safety of a drug and are a necessary hurdle for a drug to reach the market. Conducting such trials on humans would be ideal, but due to stringent ethical standards, patient availability, and limited funding, testing drug efficacy is mostly conducted on animal models. Therefore, it is considered critical to minimize the difference between human and animal disease models to accurately verify the effectiveness of the drug being tested.
The research team analyzed the aggregate disease symptoms observed in human and mouse models using big data. Unlike conventional research that is conducted based on genomic sequence of orthologous genes across species, this study focused on the tissue-specific gene expression patterns and the gene regulatory networks they form. Experimental analysis confirms that when the gene regulatory network of two species differ between human and mouse models, the mutation model of the target gene is not suitable for studying the human disease. Furthermore, analyzing the rewiring of the regulatory networks in human and mouse models help select an animal model that mimics the human disease with higher accuracy.
The work, entitled Evolutionary rewiring of regulatory networks contributes to phenotypic differences between human and mouse orthologous genes, was published recently in Nucleic Acids Research.