Helping researchers and clinicians unlock single-cell biology to enable the discovery, development, and delivery of precision medicine
When developing therapeutics for complex diseases like cancer, it is critical to have detailed information about both the disease and therapeutic in order to effectively treat patients. Although many current technologies measure aspects of cells at the population, or “bulk”, level, this approach leaves out details that are important for both understanding disease processes and developing safe and efficacious therapies. First, a richer understanding of cancer can be translated to the clinic and improve treatment regimens. In cancer, clones evolve and generate genetic and phenotypic diversity. Understanding both at a single-cell level provides researchers with a detailed understanding of clonal architecture. This in turn can be used to design personalized treatment strategies that minimize risk of relapse. Conventionally, genotypic and phenotypic parameters are measured independently, requiring complex data integration to make general correlations. Additionally, because conventional genotypic approaches measure analytes in bulk, they lack information about clonal structure. Tapestri solves this issue by measuring genotype and immunophenotype (cell-surface proteins) in the same individual cells, effectively characterizing tumor heterogeneity with unprecedented resolution. On the therapeutic side, cell and gene therapies (CGTs) hold considerable promise for treating cancer and other diseases. Cell-based therapies are often genetically manipulated by either virus or gene editors. However, these manipulations result in heterogeneity. Bulk assays are often used to characterize these cells, but details are often lost in “average” readouts. Tapestri is capable of measuring virus and gene editing multiple parameters at a single-cell level. This provides a high-resolution analysis about genetically engineered therapeutic products.
The Tapestri Platform provides clear and observable insights into the relationship between genes and the cells-surface proteins, providing a much more complete view of clonal architecture. Specifically, Tapestri enables comprehensive and simultaneous study of genomic variants and correlated protein profiles at the single-cell level — an industry first. This includes analysis of single-nucleotide variants (SNVs), copy number variations (CNVs), co-mutation, zygosity, and cell-surface protein information. With these capabilities, researchers can connect a cell’s immunophenotype with its genotype, helping them characterize clones, identify minimal residual disease, and reveal mechanisms of resistance. Tapestri offers hematological and solid cancer-specific panels. These panels enable scientists to examine specific regions in oncogenes and tumor suppressors at high resolution, so that the genomic diversity in a variety of cancers can be easily mapped out. Panels can also be customized in minutes using the Tapestri Designer software. To investigate genotype and immunophenotype simultaneously, DNA panels can be paired with oligo-conjugated antibodies that specifically bind to cell-surface markers. For cell and gene therapies, the Tapestri Platform can analyze edits made by gene editors like CRISPR (on- and off-target edits, translocations, multiple edits per cell) as well as manipulations using virus vectors (transduction efficiency, vector copy number).
Tapestri is the first and only commercially available solution that can analyze both the genotype and phenotype simultaneously from the same cells. Conventional methods of analyzing cell genotype and phenotype use separate assays. These assays are often done in bulk, such that only population-level metrics are reported instead of single-cell measurements. This means that any information regarding single cells — such as which mutions co-occur with others— must be inferred. Additionally, complex data integration from separate genotypic and phenotypic assays can complicate analysis. By contrast, Tapestri combines multiple assays into a single streamlined workflow, so that genetic information and cell-surface proteins are measured in the same cells simultaneously. This reveals direct, clear connections between cell genotypes and phenotypes. Because the data generated from this analysis is coming from one source, there’s no longer a need to speculate on how these elements are related. Multimodal analysis provides precise, accurate, and clear insights into the relationships between different parts of the cell, helping researchers to make significant discoveries that can advance the cause of human health.
In the last year, Mission Bio has seen incredible growth in the number of peer-reviewed studies — now numbering 25 to date — that have made use of the Tapestri Platform to unlock key understandings about the mechanisms of disease, often providing insights that can help pave the way for novel therapies that would have previously been unheard of. Below, you will find links and details to a small sampling of these published studies: Evolutionary predictability of genetic versus nongenetic resistance to anticancer drugs in melanoma (https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00281-6) Published in Cancer Cell, researchers used the Tapestri Platform to probe genetic and non-genetic mechanisms of resistance play in BRAF-mutant melanoma after treatment with the combination therapy dabrafenib-trametinib. PIK3CA and CCM mutations fuel cavernomas through a cancer-like mechanism (https://www.nature.com/articles/s41586-021-03562-8) Published in Nature, the Tapestri Platform was used in this study to help uncover the molecular mechanism of fast-growing cerebral cavernous malformations (CCM), a poorly understood yet aggressive disease that impacts 0.2% of the population and can lead to strokes and seizures. Single-cell DNA sequencing reveals complex mechanisms of resistance to quizartinib (https://ashpublications.org/bloodadvances/article/5/5/1437/475393/Single-cell-DNA-sequencing-reveals-complex) Published in Blood Advances, this study led to an understanding of why some patients with acute myeloid leukemia are resistant to treatment with the FLT3 inhibitor quizartinib, opening up the possibility for personalized medicines to overcome this resistance in the future.
Mission Bio’s technology broadens the understanding of how diseases function at the cellular level. By linking genotype and phenotype in single-cell analysis, at scale, these understandings can enable pharmaceutical companies to develop the next generation of precision medicines, and deliver them to the right patients.