NEW YORK – Swedish biotechnology firm Cartana is poised to grow its product portfolio and raise its profile thanks to its participation in several new Human Cell Atlas projects.
The Solna, Sweden-based company is currently expanding from offering in situ sequencing services to selling kits, and stands to benefit from such projects. As part of this change, in January it also named a new CEO, Mårten Winge, to manage commercialization. Winge had served as COO since September.
According to Winge, Cartana's participation in the Human Cell Atlas project is an opportunity for the firm to prove its mettle under the scrutinous eye of top scientists, as well as to participate in groundbreaking work that should also invigorate R&D, boost kit sales, and butter up investors.
"This is a really attractive way of being invited to the forefront of where this technology is moving and where this technology is being used," said Winge. "It's also a chance to coauthor significant papers and a fantastic opportunity to get feedback from world-class scientists."
Success in turn will help the firm win over new customers. "A lot of credibility of the technology is established by writing significant papers," Winge noted. "That can be used in marketing messages," he said. "It shows the technology is accepted, appreciated, and also something that other people are likely to be interested in."
Cartana was established in 2017 to commercialize technology developed in Mats Nilsson's laboratory in Sweden's Science for Life Laboratory, or SciLifeLab. The firm is headquartered on the campus of the Karolinska Institutet north of Stockholm and employs 15 people. Cartana's technology relies on barcoded padlock probes to target genes. After targeting cDNA, the probes are amplified in situ via rolling circle amplification. This is followed by sequencing-by-ligation step, also directly on the tissue. This enables targeted in situ sequencing at single-cell resolution.
According to Malte Kühnemund, who served as Cartana's first CEO until the appointment of Winge earlier this year, the company has worked to move beyond offering spatial transcriptomics as a service to offering library preparation kits to academic laboratories and pharmaceutical companies in Europe and the US. "That has been one of the major developments over the last year," said Kühnemund, who has now become executive vice president of R&D at the company. "Our main business will be reagent kits from now on, though we will continue the service."
It is here where Cartana's product development plans intersect with its participation in the Human Cell Atlas projects. In January, the European Commission announced funding for six European Human Cell Atlas projects to contribute to the global Human Cell Atlas initiative. Each of the pilot projects received approximately €5 million ($5.4 million) in funding through the EU's Horizon 2020 program.
Cartana is a full partner in three projects. The first, "Discovering the cellular landscape of the airways and the lung" (discovAIR), aims to develop a first draft of the Human Lung Cell Atlas, and will rely on molecular profiling of lung tissue cells with spatial mapping of cell states, 3D reconstruction of lung tissue architecture, and molecular phenotyping of cellular neighborhoods. The project is led by investigators at University Medical Center Groningen in the Netherlands and is set to run through December 2021. The EU contribution to Cartana is €172,000.
The second, "Molecular atlas of the brain across the human lifespan" (BRAINTIME), is being led by researchers at Karolinska. It will involve analysis of the developing human brain to generate an atlas of cell populations in healthy adulthood, aging and neurodegenerative disease. New cell type maps will be embedded in 3D contexts and in temporal models by using cell-fate tracking tools, spatial analysis such as Cartana's platform, and monitoring cell-cell interactions. The EU contribution to Cartana for BRAINTIME is €100,000.
The third project to involve Cartana, "Human gonad developmental cell atlas" (HUGODECA), has a similar budget and will also run through December 2021. Led by researchers at Inserm, the French National Institute of Health and Medical Research, the project will rely on single-cell profiling, spatial transcriptomics, 2D mass cytometry, and 3D imaging to unpick healthy gonadal development in culture models, as well as to assess the consequences of altering signaling pathways to mimic sex development disorders. The EU's contribution to Cartana is €206,000.
In each project, Cartana will assist in taking single-cell data, selecting marker genes that define specific cell types, and then mapping those cell types in the tissue sample to make spatial cell type maps.
There are numerous players in the spatial transcriptomics space, including NanoString Technologies, 10x Genomics, and BioSpyder, to name a few. Kühnemund suggested that Cartana was selected over competitors because of cost and throughput benefits.
"We can do a thousand genes in one sample, at single-cell resolution, and in a high throughput," noted Kühnemund. "This makes us pretty unique right now and optimally suited to cell type mapping of single-cell RNAseq data in tissue samples."
According to Kühnemund, prices can vary, but cost per sample on the Cartana platform can range from €500 to €1,000.
SciLifeLab's Nilsson also suggested the technology has some inherent advantages for researchers. "We have found that the targeted in situ sequencing method that we have developed over the years is really very useful for spatial mapping of molecularly defined cell-types," Nilsson said. "A typical question researchers have after completing a single-cell RNA sequencing effort where cells are clustered to molecularly defined cell-types is, 'How are they spatially organized in the tissues that we extracted them from?'" he said. "This is the question that can be addressed using our method."
While Cartana stands to pocket about half a million euros from participating in the three projects, it will also use its experience to develop new products.
"Of course, working on these different kinds of tissues we gain more experience also on developing better protocols for those tissue types," said Kühnemund. "And a major outcome from this project is that we will develop and validate cell-type panels for the different tissue samples," he said. "That is our aim, to provide panels for all cell types in the human body."
Alain Chedotal, the Inserm investigator leading the Human Gonad Developmental Cell Atlas project, said his project aims to map cell types across tissues as well as across the sex determination process.
"We wish to understand how an embryo, which initially looks the same regardless of sex, becomes male or female," Chedotal said. "The chromosomes are different, of course, one is XX, the other XY, but phenotypically, after six weeks of gestation, you cannot tell male from female," he said. "Two weeks later though, everything becomes different."
To understand these processes, the researchers will combine techniques to both identify cell types, as well as to map the cells in the developing body or embryo. Chedotal noted that they could use antibodies, where they exist, to map proteins, but often such antibodies are not even available. This is why the researchers turned to spatial transcriptomics and Cartana's platform. "We want to use Cartana's technology to identify cell types and to map them in the developing embryo," he said. He noted that he became familiar with Cartana through scientific meetings.
In addition to Cartana, Inserm is working with academic partners in Sweden, Denmark, and the UK. Other industry partners are Miltenyi Biotec and Keen Eye Technologies, a Paris-based healthtech company that specializes in using AI for bioimaging and the analysis of imaging data.
While the project officially commenced in January, it has been slow going as of late, as most of Europe locks down in response to the global coronavirus pandemic. Chedotal said that software engineers and others who don't need to be in the wet lab have been able to work from home in recent weeks. The project also has enough data at hand to keep people occupied for now.
"But future analyses are problematic," said Chedotal. "Our institute is closed and we can't move from home, so it's not an easy situation," he said. "If it lasts only one month, then it's okay," he added. "But if it lasts six months, then it will be a nightmare."
If the shutdown continues, he said, the EU might need to consider extending the two-year project accordingly.