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Startup ReadCoor Plans to Launch In Situ Sequencing Platform Next Year

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NEW YORK (GenomeWeb) – ReadCoor, a spinout of the Wyss Institute for Biologically Inspired Engineering at Harvard University, said this week that it plans to launch an in situ sequencing platform next year based on technology originally developed in George Church's laboratory at Harvard.

To support these efforts, the company recently raised $23 million in a Series A financing round led by Decheng Capital.

ReadCoor CEO Shawn Marcell told GenomeWeb that the firm plans to offer its fluorescent in situ sequencing (FISSEQ) technology as a service in the next month. It has also developed a platform for in situ sequencing, which it will launch next year on a limited basis, he said.

The company is based in Cambridge, Massachusetts, and Marcell said the next steps are to establish its laboratory space and processes, and finish an initial round of hiring. By the end of the year, he expects ReadCoor will have around 15 employees. The recent financing should get it through the next year or two.

Researchers from Harvard published a proof of principle of FISSEQ in Science two years ago. The method is similar to the DNA nanoball and sequencing-by-ligation method that was used by Complete Genomics, except that tissue is the sample input, rather than DNA or RNA.

Richard Terry, co-founder of ReadCoor and the company's president and chief technology officer, told GenomeWeb that the principal is essentially the same as described in the Science paper with the main difference being that the team has now built a fully automated platform.

In order to sequence in 3D, RNA molecules within cells are first immobilized and primed to perform reverse transcription to make cDNA. As part of the reverse transcription step, the researchers incorporate crosslinking groups to "lock those cDNA molecules in place," Terry said. They then perform rolling circle amplification to generate rolling circle colonies, or "rolonies..

"We now have in situ a library of RNA molecules that have been converted to cDNA and amplified using rolling circle amplification," he said. Instead of putting those rolonies on a substrate and sequencing them outside of the cell and tissue, "we're able to generate the library within the tissue sample" and it can then be sequenced using optical-based NGS chemistry, Terry said.

Marcell said that the initial platform uses conventional sequencing-by-ligation chemistry, but that the team has since developed an improved version, which it calls sequencing by structured ligation. That method is about five times faster than standard sequencing by ligation, Marcell said. He said the initial commercial platforms would likely run using the standard sequencing-by-ligation method, but subsequent upgrades would include ReadCoor's method.

The platform itself is around the size of an Illumina HiSeq system and includes microscope-style automated optics, similar to other NGS instruments, Terry said. It is compatible with fresh frozen or formalin-fixed paraffin-embedded tissue, and its throughput varies depending on a number of different metrics including the tissue type and the specific scientific questions. Previously, the researchers reported read lengths of up to 30 bases. Terry said that the commercial system would have both longer and shorter read length options.

Although the initial proof of concept described sequencing RNA sequencing, Marcell said that the platform is "panomic," and can sequence RNA, DNA, even antibodies or aptamers. But, he noted, "the big hole in the market is RNA." Conventional NGS provides the sequence of RNA molecules but "doesn't tell you their location or let you overlay morphology," he said.

With FISSEQ, he said, researchers will be able to get sequence information, the location of each read, and a high-resolution 3D image with the reads mapped in the image.

The technology could have a number of applications, Marcell said, for instance in comparing healthy and diseased tissue. Researchers from the Wyss Institute are already using it to map the brain's neural circuits under a $21 million grant awarded by the Intelligence Advanced Research Projects Activity in January. Marcell said that ReadCoor would now take on much of that work.  He added that the firm also has a couple of other projects in the pipeline related to gene therapy, pathogen identification, and breast cancer research.