Takara Bio USA, Inc. recently announced its acquisition of Curio Bioscience, a strategic move that expands its portfolio of single-cell next-generation sequencing (NGS) solutions with spatial biology tools. By integrating Curio Bioscience’s cutting-edge spatial profiling technologies, Takara Bio aims to bridge the gap between single-cell analysis and spatial multiomics, offering researchers an enhanced understanding of cellular interactions within tissues.

Andrew Farmer is the CSO and head of research and development at Takara Bio USA, Inc. Andrew joined Takara Bio USA (formerly Clontech Laboratories) in 1998 as the developing scientist for Tet systems. He was also responsible for inventing recombination-based cloning technology known as the Creator System. Over the years, he has been responsible for the development of several product lines, including two-hybrid systems, viral delivery and inducible expression systems, and the In-Fusion® Cloning system. Most recently, Andrew led Takara Bio USA’s development of its NGS product line—notably, its suite of ultra-low input RNA-seq products. 

Christina Fan is a pioneer in spatial, single-cell, and molecular-counting technologies, and was co-founder and CTO of Curio Bioscience. Previously at Cellular Research, she invented a high-throughput single-cell transcriptome analysis technique that led to the company’s acquisition by Becton Dickinson (BD). She subsequently led the technical team to help bring single-cell technology to the market. As a graduate student at Stanford, she co-invented methods to measure fetal aneuploidy from maternal blood that were later licensed to Verinata/Illumina. Her work directly led to the noninvasive prenatal field we know today. 

Drug Discovery News recently spoke to Farmer and Fan to learn more about the acquisition and how the combination of Takara Bio’s and Curio Bioscience’s technologies will enable scientists to explore gene expression, chromatin accessibility, and molecular interactions in a spatial context – ultimately driving new discoveries in biomedical research.

How does the acquisition of Curio Bioscience enhance Takara Bio's existing single-cell tools?

Andrew: Takara Bio offers diverse life science products and services, supporting discovery, translational, and clinical scientists to advance their research. We are proud of our history as an innovator in the single-cell space, developing the first commercial products for single-cell DNA and RNA sequencing.

The Curio Bioscience acquisition continues this legacy with the addition of spatial profiling, including Trekker – the first truly single-cell spatial technology. Curio’s advanced Trekker and Seeker technologies extend the power of Takara Bio’s NGS solutions by enabling researchers to convert single-cell sequencing data into spatially resolved maps. This provides high-resolution information into the organization and function of cells within their native tissue environments. Adding spatial biology to Takara Bio’s portfolio broadens the array of applications supported by our complementary NGS tools, which help researchers answer key questions at all levels – from bulk to single-cell and now spatial analysis. This combined analytical view will provide researchers with deeper biological insights.

What are the key features of Curio Bioscience's Trekker and Seeker technologies? 

Christina: The two product lines Curio has developed aim to make it easier for labs to access spatial multiomic measurements. Both Seeker and Trekker are reagent-only solutions, requiring no specialized instrumentation, and both use NGS, which is widely available.

Seeker, the first product launched by Curio, uses spatially barcoded substrates that capture and spatially label transcripts in tissue sections from any species at near single-cell resolution. This provides whole-transcriptome coverage for an unbiased look at gene expression.

Curio’s newest technology, Trekker, fits into a novel class of spatial multiomic techniques. It allows the direct measurement of the position of a single cell in a tissue section by spatially tagging individual nuclei with DNA barcodes. By incorporating the one-hour Trekker protocol in front of a conventional single-cell workflow, researchers can easily transform any single-cell experiment into a spatial measurement. This enables research to go beyond spatial transcriptomics (gene expression patterns) into spatial multiomics (DNA instability, chromatin accessibility, and more).

How do Curio Bioscience’s Trekker and Seeker technologies complement Takara Bio's NGS solutions? How will the integration of technologies provide deeper insights into tissue spatial organization and molecular composition?

Andrew: Fundamentally, Seeker is a bulk NGS assay – RNA transcripts can be analyzed from the entire population of cells at once instead of from single cells. This opens the possibility of adapting Seeker to multiple bulk NGS assays that Takara Bio has strength in, such as RNA-seq with full gene-body coverage and immune profiling. As the recognized industry leader in sensitivity for gene detection in single-cell assays, we see the potential to not only expand the applications of the Seeker assay but also enhance its sensitivity.

Trekker technology can be applied upstream of essentially any single-cell analysis. This makes it compatible with a broad array of single-cell methods available in the marketplace, in addition to Takara Bio’s solutions. One of our solutions is high-throughput Shasta™ Total RNA-Seq technology, which can generate whole-transcriptome libraries from up to 100,000 cells. Shasta Total RNA-Seq enables highly sensitive RNA-seq with full gene-body coverage, providing the ability to detect transcriptional isoforms and gene fusions. Linking Shasta and Trekker technologies will let researchers analyze more cells in their spatial context, find more biomarkers, and make more discoveries.

What challenges in spatial multiomics and single-cell analysis do the Trekker and Seeker platforms overcome?

Christina: One major challenge in spatial multiomics is accessibility. Typical spatial instrumentation requires high capital expenditures, and the complex data analysis inherent to using these platforms is a burden for many labs.

Both Seeker and Trekker address accessibility by eliminating the need for expensive instruments. And, because both methods require minimal tissue optimization, the learning curve is shallow, and start-up time is short.

In addition to accessibility, other challenges in spatial genomics include species compatibility and sample throughput. Seeker provides a quick, highly detailed snapshot of the spatial organization of gene expression from any higher-order organism. Beyond analyzing human and mouse samples, our customers are obtaining spatial transcriptomics information from octopus, fruit fly embryos, and other interesting organisms. In addition, Seeker’s simple workflow enables higher sample throughput than other microscopy-based spatial platforms, making it possible to be used in studies that require larger numbers of samples. 

As a different class of spatial solution, Trekker brings together established single-cell analysis and spatial information. Other spatial techniques based on capture arrays or microscopy are not designed to pinpoint the specific contributions of individual cells within their spatial context, requiring the use of complex algorithms to infer the contribution of spatial signals from single cells. Trekker’s direct measurement of the spatial positioning of nuclei simplifies the analysis by eliminating the need for complex algorithms or the merging of separate spatial and single-cell datasets. 

What future developments can be expected from Takara Bio following this acquisition?

Andrew: In the short term, we aim to continue the great work the Curio team has started in adapting Trekker to a broad array of available single-cell methods. Currently, Trekker is directly supported for 10x Chromium™ 3′ RNA-seq and BD Rhapsody™ whole-transcriptome analysis. We are working to build on user-demonstrated protocols to develop supported Trekker protocols and kits for Fluent PIP-Seq™ V, 10x Chromium Epi Multiome ATAC + Gene Expression, and Scale Bio’s Single Cell RNA Sequencing Kit. We will also be working towards protocols that join Trekker with Takara Bio’s single-cell chemistries, such as Shasta Total RNA-Seq. In the case of Seeker, immediate plans are to enhance the library prep protocol with Takara Bio enzymes and add greater sample barcoding support with our unique dual indexes.