SBIR Phase I: Physical Cellular High Content Screening Using a piggyBac Transposen System

This Small Business Innovation Research (SBIR) Phase I project will address the demand for new and evolving approaches to alleviate shrinking drug pipelines and costly failed human safety trials and recalls by implementation of new technologies to transform complex human stem cell-derived neural cultures into informative temporal high content screening (HCS) assays. A robust means to interrogate complex cell cultures is important since it is believed that many diseases, drug side effects, and environmental phenotypes are the result of multi-cellular interactions that have been disrupted, leading to physical changes at the complex cell/tissue level. Extended studies toward improving differentiation to specific neural phenotypes and translation of developed techniques will include cell types beyond neural cells. The proprietary expertise in developing scalable manufacturing systems is key to the success of a robust cellular HCS for neural and other cells. Published studies using the company's proprietary neural cells in HCS assays demonstrates utility of the human cell platform, and reported transformative results indicative of human pluripotent-sourced cells that are of significant importance. The broader impact/commercial potential of this project are that it will provide alternatives to animal model testing through development of novel human stem cell-based assay systems that provide potentially more predictive and translational outcomes for drug discovery. Previously, gene targeted rodent models transformed our understanding of how genes control or affect mammalian development and disease. The robust HCS amenable adherent proprietary neural cells combined with new technologies will enable transformational human cell-based assays that edit, knockout, or knock-in any genome sequence before or during the HCS. As industry and academic researchers move forward in their quest to enhance their understanding of human development and diseases, discover novel therapeutic compounds and develop improved tests for toxicity, so will demand for relevant sources of research materials. Successfully facilitating complex high content system assays at reduced cost while improving throughput also will limit assay variability. This will be met with keen commercial interest from Pharma, chemical companies, CROs and academic and government researchers. Anticipation is that the proposed new genetically modified cellular products will shorten development lead times in early phase compound assessment programs compared to animal studies and provide more robust and informative compound information than current in vitro assays.