The emerging field of spatial genomics can fuel precision medicine by creating detailed genomic maps of tumors and other tissues. Here are five burgeoning startups bringing new innovations to the space.
An explosion in DNA sequencing technology has dropped the price of reading the genome over the last two decades. Next-generation sequencing provides rich information about the genetic makeup of a patient in addition to flagging up genetic variants potentially linked to disease. For this reason, genomics is key for diagnosing rare diseases, discovering novel drug targets, and targeting treatments to patients, especially in the case of cancer.
One disadvantage of conventional DNA sequencing is that tissue samples are typically broken up in order to access the genetic material inside cells. This means that the spatial information of the tissue, which can contain vital context in heterogeneous tissue samples such as solid tumors, is lost. This approach can also remove key spatial information about the biology of what is going on within a cell.
To provide the required spatial context, researchers have often deployed tissue and cell imaging techniques such as immunohistochemistry, immunofluorescence, and in situ hybridization. However, these methods are often limited to providing information about several genes or proteins at a time.
Spatial sequencing is an emerging field that blends the vast datasets provided by next-generation sequencing with the spatial context. This allows researchers to map out genomic, transcriptomic, and proteomic data within cells and tissues, expanding their knowledge of how diseases develop.
Spatial genomics in particular can be a vital tool in studying diseases. Although all of our cells have the same genetic code, that genetic material is organized and packaged in different ways. This can influence which genes are turned into proteins in each cell. In cancer, for example, spatial genomics can be used to tease out genetic variation in non-coding regions of the genome that lead a cell to turn malignant.
Spatial genomics is gaining traction as the costs of DNA sequencing and lab automation fall, with major hubs including the U.S., the U.K., and Sweden. Some of the big names in the field include Nanostring, 10X Genomics, and Bruker. We have highlighted five flourishing companies that are pushing the boundaries of spatial genomics.
1. Arima Genomics
Founded: 2015 | Headquarters: Carlsbad, California, U.S.
Arima Genomics specializes in investigating how DNA is spatially organized in chromatin within a cell, also known as 3D genomics, using a method called Hi-C proximity ligation. In this procedure, chromatin is fixed in its 3D shape. The DNA is then cut using restriction enzymes, and sequences that are near to each other are sequenced together.
Proximity ligation lets users analyze genetic variants that can contribute to disease, even if the genetic variant is in a non-coding region of the genome. This is because the 3D structure of the genome means that changes to one site might impact which genes are activated on another site if they are close to each other when the DNA is folded.
The main applications of Arima’s technology include life sciences research and human health. By detecting spatial relationships within the structure of the genome, the company can help users to discover new biomarkers and drug targets. For example, researchers used Arima’s Hi-C technology to identify chromosomal rearrangements linked with ependymoma tumorigenesis.
Arima secured $7 million in March 2022 to finance the development of its technology in addition to the growth and commercial expansion of the company. In January 2023, the firm joined the Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative to help researchers to carry out single-cell sequencing in brain cells. More recently, Arima has teamed up with Protean BioDiagnostics and Velsera to use its technology in precision medicine and diagnostics.
2. Cantata Bio
Founded: 2022 | Headquarters: Cambridge, Massachusetts, and Scotts Valley, California, U.S.
Cantata Bio was formed out of a merger between the metagenomics player Arc Bio and Dovetail Genomics, which specializes in 3D genomics research.
Like Arima Genomics, Cantata’s 3D genomics division aims to help researchers discover disease mechanisms by unpicking the spatial arrangement of DNA within the cell. To do this Dovetail sells Hi-C proximity ligation kits that let users analyze genetic variants that are interacting in 3D space and enhancing or silencing gene promoters. Alongside standard next generation DNA sequencing approaches, Cantata’s kits can boost research in applications including epigenetics, evolutionary biology, and cancer.
Leading up to the merger with Arc Bio, Dovetail Genomics signed a partnering deal with Singular Genomics in January 2022, and licensed its kits to GenDx in June. At the same time as the debut of Cantata Bio, the Dovetail team launched its latest TopoLink kit, which is designed to halve the time researchers spend processing samples for Hi-C proximity ligation—down to six hours compared to the roughly 12 hours required for traditional Hi-C approaches.
3. Ochre Bio
Founded: 2019 | Headquarters: Oxford, U.K.
Ochre Bio was named in honor of the work of Nobel Laureate Sydney Brenner. The late scientist discovered three types of stop codons in the genome, dubbed Amber, Opal/Umber, and Ochre.
The firm is focused on the development of RNA therapies for liver diseases, which often have liver transplant as the last resort treatment. To help discover targets for these conditions, Ochre Bio has generated a trove of spatial genomics and single-cell sequencing data derived from more than 1,000 donated human livers and is constructing a human liver in silico for use in drug discovery.
In October 2022, Ochre Bio raised $30 million in Series A financing to fund the development of drug candidates based on its spatial genomics research in human livers. The firm will then test its first RNA therapeutic candidates in facilities across the pond in the U.S.
4. S2 Genomics
Founded: 2016 | Headquarters: Livermore, California, U.S.
S2 Genomics focuses on the development of sample preparation systems to speed up sequencing of genetic material in a single cell. This form of sequencing provides a higher resolution than DNA sequencing in whole tissue samples, but is harder to carry out due to the lower amount of starting material.
Via its Singulator 100 System, S2 provides an automated method for harvesting single cells from solid tissue samples more reliably than current methods, while causing less stress to the cells. The firm is currently rolling out Singulator 100 throughout Europe, and its latest target market is the Iberian Peninsula via a partnership with Bonsai Lab forged in January 2023.
S2 Genomics is also developing a way to link single-cell sequencing with spatial genomics. One common disadvantage of single-cell sequencing is that it can’t reveal where cells were located in the tissue prior to extraction. S2’s technology overcomes this limitation by allowing single cells to be tagged with a location barcode in the form of oligonucleotides.
5. Single Technologies
Founded: 2014 | Headquarters: Stockholm, Sweden
Single Technologies was formed in a collaboration between specialists in life sciences and the fiber optical grating industry. Current next-generation sequencing techniques have a limited number of dimensions and channels to process samples. This is insufficient for spatial sequencing, which can require vast numbers of sequences to be captured from different locations on a 3D tissue sample.
Single Technologies’ sequencer Theta is designed to address this need with image-based sequencing. The company hasn’t revealed the details of how the device works, but explains that Theta employs nanofluidics and confocal microscopy that can detect single molecules. The device is able to sequence DNA molecules in 3D tissue samples and at the scale required by spatial genomics.
To finance the development of its technology, Single bagged SEK 50 million ($5.9 million) in investments from local investors in December 2020.
Jonathan Smith is a freelance science journalist based in the U.K. and Spain. He previously worked in Berlin as reporter and news editor at Labiotech, a website covering the biotech industry. Prior to this, he completed a PhD in behavioral neurobiology at the University of Leicester and freelanced for the U.K. organizations Research Media and Society of Experimental Biology. He also has an undergraduate degree in neuroscience and worked at the pharmaceutical company Eisai for one year on a student placement.