Tuesday, April 1, 2025
4/1/2025
Pioneering assays for spatially-resolved single-cell multiomics - Project Summary: Disease often stems from cellular dysfunction, and single-cell transcriptomics has been instrumental in unveiling the incredible diversity of cell types and advancing our understanding of their roles in health and disease. Yet, cells do not operate in isolation. Recognizing the spatial relationships between cells, in addition to their individual molecular profiles, offers crucial insights into cellular organization and communication, revealing the intricate networks that underlie both normal development and disease pathways. These intercellular dialogues serve as the foundation for most disease progressions and can be targeted to gain insights and potentially reverse the disease course. At Survey Genomics, we have developed Cytope-drop, an innovative approach for spatial barcoding of individual cells that enables high-throughput spatially-resolved multiomics (transcriptome, cell surface proteins, etc.). Cytope-drop integrates with existing droplet-based single-cell sequencing workflows, delivers gold-standard single-cell multiomic data, and does not require additional capital equipment. In this resubmission, we propose to further increase the spatial resolution of Cytope-drop to 50-um, scale manufacturing capabilities, and achieve FFPE sample compatibility. Through these activities, Survey Genomics aims to bring to the market a product that enables researchers to perform single cell analysis while obtaining spatial context simultaneously. Cytope-drop compares favorably to a number of approaches that have emerged for spatial transcriptomics. Current sequencing and imaging based spatial transcriptomic approaches focus on localizing transcripts, whereas Cytope-drop focuses on localizing cells and obtains mRNA abundances, protein abundances, and cell locations for the same cells in a single assay. Compared to existing commercially available spatial transcriptomics methods, our approach stands out in several key ways: 1) no capital equipment costs, 2) delivers true single-cell molecular profiles, 3) multimodal data (including RNA expression, protein expression, chromatin accessibility, etc.), 4) high-throughput capacity, and 5) compatibility with current single-cell processing techniques. In summary, our proposal aims to develop and commercialize the only platform to-date that delivers mRNA abundances, protein abundances, and cell locations for the same cells in a single assay. Survey Genomics is uniquely poised to deliver on the proposed aims with our world-class team extensively experienced in single-cell and spatial genomics, established manufacturing and financing partners, and strong IP position. True single-cell data with spatial context, low cost, and high throughput position Cytope- drop as a compelling approach to deliver new insights into the role of cellular organization and communication in solid cancers, autoimmunity, neurodegeneration, fibrosis, and more.
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