Research Project
9410305
Abstract The goal of Mission Bio, Inc. is to develop instrumentation that will accelerate the investigation of cellular heterogeneity relevant to human health by rapidly and accurately analyzing nucleic acids from single- cells. The impact of cellular heterogeneity on biological function and disease is crucially important to a variety of questions in oncology, immunology, stem cell biology and infectious disease. Through the analysis of individual cells within a mixed population, it is possible to identify unique cell populations or cell states critical to human health and development, that are otherwise unobservable by ensemble measurements. In proof-of-concept work, we developed a new single-cell sequencing technology, Mosaic, which is highly differentiated from existing approaches. Mosaic performs molecular barcoding on the nucleic acids of thousands of individual cells confined to microfluidic droplets. Following bulk sequencing, the molecular barcodes are used to reassemble in silico the genetic or transcriptional profiles associated with individual cells. The principal advantage of the Mosaic platform is the unique ability to perform multi-step droplet processing to prepare genomic DNA or RNA for efficient molecular barcoding. No technology with similar sequencing capability and throughput currently exists in the marketplace. The intellectual merits of the Mosaic approach stem from the core ability to deliver a rapid and low-cost solution for massively parallel single-cell genome and transcriptome analysis on large heterogeneous populations of cells. Commercialization of the Mosaic system will enable a more detailed and comprehensive analysis of the genomes and transcriptomes of these rare cell populations. Our objective in this Phase II proposal is to take the basic Mosaic platform and ready it for commercialization by further optimizing numerous critical performance metrics such as allele dropout rates, sequence error rates and multiplexing capability. We will also fully validate the Mosaic approach for a clinically relevant application investigating genetic variation in acute myeloid leukemia (AML). Mosaic relies on demonstrated microfluidics and a solid foundation of intellectual property. Phase II funding will result in a needed and technically achievable research and diagnostic tool with high impact potential in the biomedical marketplace.
