Whole Animal Microplate Assay for Toxicity Screening

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DESCRIPTION: (provided by applicant) frequently fail subsequent whole animal testing, underscoring the need for a rapid, inexpensive whole animal toxicity test that can be performed early in the drug development process. Zebrafish has a morphological and molecular basis of tissue and organ development similar to that found in humans and is an ideal, vertebrate animal model for toxicity testing. In contrast to mice and rats, zebrafish are inexpensive to breed, undergo rapid embryogenesis and are easy to analyze because their embryos are transparent. Furthermore, drug delivery is simple and good dose responsiveness to toxicity has been observed. Currently zebrafish toxicity assays use lethality, embryo survival rate, behavior and microscopic examination of organ malformation as general parameters for assessing toxicity. However, for large-scale toxicity screening, qualitative visual inspection is unsuitable. Using zebrafish, this SBIR aims to develop a quantitative, whole animal ELISA-type assay to measure liver and gut development and function after drug treatment. Phase I research will validate the assay using compounds with known toxicity effects and investigate automation of the assay. A rapid, quantitative assay for screening compounds for developmental organ toxicity will facilitate selection of lead compounds for further drug development. PROPOSED COMMERCIAL APPLICATION: By providing a rapid, quantitative, and inexpensive method for organ toxicity testing, the zebrafish assay will facilitate drug screening and toxicity testing in the pharmaceutical and chemical industries. The worldwide markets for drug screening and toxicity testing are estimated at $700M and $500M, respectively.