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Harvard Spin-Off to Sequence, Visualize RNA in Tissue

Breast cancer tissue analyzed with Fisseq

Breast cancer tissue analyzed with Fisseq, where each spot represents one base of an RNA transcript localized in 3-D in the tissue. (Wyss Institute, Harvard University)

28 September 2016. A new spin-off enterprise from Harvard University is commercializing technology that enables sequencing and imaging of genetic transcriptions of cells in their original tissue. The company, ReadCoor Inc. in Boston is also raising $23 million in its first venture funding round.

ReadCoor plans to advance and market techniques known as fluorescent in situ sequencing, or Fisseq, originally developed by and licensed from the Wyss Institute for Biologically Inspired Engineering at Harvard University. Fisseq combines the sequencing of RNA, nucleic acids transcribed from genetic codes in DNA, with three-dimensional spatial imaging to provide a more detailed analysis of biological processes in cells, without removing the cells from tissue. Harvard Medical School geneticist and Wyss Institute faculty member George Church and colleagues describe Fisseq in a March 2014 Science article.

The company says Fisseq converts RNA into a DNA copy at its original cellular location, where it is immobilized and amplified. The amplified DNA copies are then fluoresced and cross-linked in a 3-D matrix. This technology, says ReadCoor, makes it possible to visualize the entire collection of gene transcripts of individual cells, as well as track uniquely identified RNA and DNA in multiple cell types, and under varying conditions.

Church, a co-founder of ReadCoor and serial entrepreneur, says in a Wyss Institute statement, “We are opening the door to a truly ‘pan-omic’ view of all biological molecules and interactions within cells and tissues, powering numerous research discoveries and clinical applications.” Wyss researchers are applying Fisseq to an analysis of breast cancer, providing insights into tumor development that they expect to publish next year. Another team is using Fisseq to trace sets of nerve cells and their connecting processes in intact brain tissue over long distances, a task difficult to achieve with other methods, funded by the Intelligence Advanced Research Projects Activity.

As a commercial technology Fisseq is expected to provide more accurate analysis of molecular pathways, to better identify and validate new drug targets. Fisseq can also be applied to medical diagnostics, such as identification of pathogens. Richard Terry, a senior scientist at Wyss Institute and co-founder of ReadCoor with Church notes, “By offering Fisseq systems, spatial sequencing services, and diagnostics to our customers, ReadCoor will give neurologists, cancer researchers, clinicians, geneticists, and others the 3-D coordinates of working genes that will inform their work in new ways.” Terry is becoming ReadCoor’s president and chief technologist.

ReadCoor is the recipient of $23 million in its first financing round, led by Decheng Capital, an investor in life sciences and health care start-ups based in Shanghai and Silicon Valley. Joining the round are Lilly Asia Ventures, Vivo Capital, and individual investor Hansjörg Wyss.

Cross-section of mouse brain

Cross section of mouse brain, visualized with Fisseq (Wyss Institute, Harvard University)

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