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Spatial transcriptomics combines cellular imaging and single-cell gene expression. For broad adoption of this methodology, scientists need an easy-to-use and robust collection of technologies. Vizgen, in Cambridge, MA, “offers an end-to-end platform for spatial transcriptomics research that consists of the MERSCOPE™ instrument, reagents, and software—all built around our proprietary MERFISH technology,” says Peter Reinhold, global product manager, assays and reagents. Advances in development at Vizgen will push spatial transcriptomics into many areas of research, including cancer, immunology, and neuroscience.
MERFISH is “the next generation of genomic technologies,” says George Emanuel, PhD, scientific co-founder and senior director technology and partnerships. “It’s able to measure RNA at a multiplexing capacity that’s relevant for really understanding the nuances of gene expression, and now it’s doing so directly in situ and preserving the original location of the RNA within the biological tissue.”
Increasing options
The Vizgen platform provides an expansive list of options. Customers design custom gene panels that can detect up to 500 genes. A verification kit is available to ensure sample quality and test the technique on specific tissues. Downstream scientists can use the MERSCOPE™ Vizualizer and Vizgen’s ongoing improvements in software tools to analyze their MERFISH data.
MERSCOPE allows more scientists to use MERFISH technology for spatially resolved transcriptomics in an easy-to-use platform. MERSCOPE “contains a high-resolution microscope and a fluidic system that together perform this automated imaging-based technology,” Emanuel explains. “So, the sample goes in this high-resolution imaging platform and highly accurate, single-molecule spatial gene expression data comes out that enables single-cell characterization across a full centimeter of tissue.” Vizgen visualization tools help scientists analyze that data.
One dataset holds a rich amount of information. “We could measure up to a billion transcripts and segment up to a million cells in one instrument run,” Emanuel says. “We can find out exactly where all the transcripts are from for each of the targeted genes.”
Opportunities in applications
The Vizgen platform is relatively new on the market, and the full extent of applications hasn’t yet been realized. As Emanuel says, “I’m excited to see what scientists can learn by applying this technology to their research.”
One scientist with many ideas ahead for MERFISH and MERSCOPE is Nicholas Banovich, PhD, associate professor in the Integrated Cancer Genomics Division at the Translational Genomics Research Institute (TGen) in Phoenix. He describes his lab’s work as “using genomics and technologies that allow us to look at gene regulation to understand a number of complex human traits.” Most of Banovich’s work focuses on pulmonary fibrosis and immunotherapies and cellular therapies to treat brain tumors.
Banovich points out that “the lung is a complex organ, and it’s highly spatially organized, but pulmonary fibrosis causes an incredible amount of cellular remodeling.” He hopes to use MERSCOPE to analyze those changes before symptoms appear and as the disease progresses.
In his work on immune-based therapies for brain cancer, Banovich plans many uses of spatial transcriptomics. “We’re using this technology to assess how immune cells are infiltrating into a tumor, what types of immune cells are infiltrating into a tumor, and comparing endogenous immune cells to an exogenous one, like a CAR T cell,” he says. “With MERFISH on MERSCOPE, we can start to look at these changes in this really robust way.”
Vizgen is already working on many advances to this technology. One is the ability to profile 1,000 genes in one MERSCOPE experiment. Another is enabling the use formalin-fixed, paraffin-embedded (FFPE) samples. “That’s going to unlock a lot of samples for many researchers, especially within oncology,” Reinhold says. In addition, future Vizgen reagent kits will co-detect transcripts and proteins.
Emanuel says spatial transcriptomics is “really an unexplored territory so far, but it is already starting to give MERSCOPE customers direct insight into what’s happening within the biological system.”
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