Technological Threefold Way Leads to Biological Wisdom

10x Genomics’ single-cell, spatial, and in situ analysis platforms can help scientists cope with biological complexity and realize healthcare improvements

This company is growing by leaps and bounds in a race with itself to help scientists improve human health. 10x Genomics’ goal is to bring scale and resolution to biology while continually pushing the boundaries of science.

“Amazing advances are on the horizon in biology, but to make them a reality, we first need to develop the best technologies to help scientists see the underlying biology,” says Serge Saxonov, PhD, 10x Genomics’ co-founder and CEO. “The biology is incredibly complex, and scientists need high-resolution technologies. So, we set out to build them.”

The company’s steadily growing product portfolio includes platforms for single-cell and genomic spatial analysis technologies. A third platform—in situ analysis—was added during the second half of 2020 when 10x Genomics acquired ReadCoor and CartaNA. These acquisitions not only add 110 patents to 10X Genomics’ portfolio, pushing the total number of patents to 935, they also exemplify how 10x Genomics views the world.

“We think diligently about where the scientific world is going, the questions scientists are thinking about now, and the questions they will be asking in the future,” Saxonov relates. “Then we form our internal conviction and work backward to identify the technology needed to make that future a reality. We invest internally and develop products, but also recognize that we don’t have a monopoly on innovation. Our acquisitions, therefore, are in the service of our long-term strategy.

“In situ analysis is an area we identified as potentially being very important several years ago. The technology wasn’t ready, though. The science behind it needed to advance, and the market needed to be ready to accept it.”

When those elements began converging a few years ago, 10x Genomics took another look. “We started internal discussions and surveyed efforts around the world,” Saxonov recalls. “ReadCoor and CartaNA each had developed deep expertise in this area and had strong intellectual property.” So, 10x Genomics approached them.

Before in situ analysis, though, there was single-cell analysis. “The cell is a fundamental element of biology, so it’s foundational in how biology needs to be done,” Saxonov insists. “Before single-cell analysis became possible, analytics was virtually blind.” Helping to address that, the company launched its first line of single-cell analysis products in 2016.

Four years later, last August, 10x Genomics made a major advance when it introduced the Chromium Single Cell Multiome ATAC + Gene Expression system. Chromium is the company’s single-cell platform. The Multiome ATAC + Gene Expression system sits atop it to analyze epigenetics and the genetic expression of RNA. It was a much-requested combination of technologies.

10x Genomics recently introduced a system that combines the company’s Chromium instrument with Chromium Single Cell Multiome ATAC + Gene Expression reagents. These system components, along with analysis and visualization software, allow the simultaneous profiling of gene expression and open chromatin.

“When you’re trying to understand a fundamental feature of human biology, you have the overall blueprint in the DNA, but only a tiny fraction of that blueprint is used for any particular cell,” Saxonov explains. “The epigenetic programming determines what type of cell it is, and the cell uses RNA molecules and protein structure to carry out its functions.” Even though many cells seem virtually identical, there is, Saxonov adds, “tremendous heterogeneity in a complex orchestra of gene networks and signaling.”

As yet, however, scientists haven’t been able to correlate the cell’s programming to how it actually behaves. According to Saxonov, scientists may discern relationships between programming and behavior if they use the Chromium Single Cell Multiome ATAC + Gene Expression system. “It is,” he says, “a Rosetta Stone that brings those two areas together to identify the function.”

The combination of two disciplines also was integral to the formation of 10x Genomics in 2012. Co-founders Saxonov, a mathematician and bioinformation expert, and chemist Ben Hindson, PhD, now the company’s president and CSO, had worked together at QuantaLife, a startup that was acquired in 2011 by Bio-Rad Laboratories.

After the acquisition, Saxonov and Hindson took some time off before eventually getting together in a San Francisco coffee shop to discuss a potential collaboration. “We started thinking about where the world of research was going and the fundamental problems that needed to be addressed,” Saxonov remembers, “and we worked backward, making some inventions.”

They raised seed money from friends and family, incorporated, and began bringing on people in multiple scientific disciplines. In 2015, 10x Genomics went commercial.

10x Genomics’ bold, collaborative, multidisciplinary approach, Saxonov declares, “is the crux of what makes us special.” He and Hindson learned the value of the cross-fertilization of ideas early in their careers, where, he said, “it was embedded in our minds.”

The influx of fresh viewpoints is fed by 10x Genomics’ clients. Typically, they are academic scientists trying to make basic biological discoveries in a variety of different systems and diseases. Now there’s also a growing contingent of biotechnology researchers. They are intent on identifying drug targets, developing drug candidates, or pursuing preclinical projects such as characterizing side effects or defining mechanisms of action.

“We’ve been seeing a lot of interest from biotechnology companies around single-cell analysis since single-cell approaches have become more common,” Saxonov notes. In one laboratory, for example, researchers were trying to discern the biology of Alzheimer’s disease. Rather than running association studies, they used single-cell analysis to pinpoint a gene that is expressed only in certain cells of the brain at a particular time. Consequently, the researchers could better elucidate the beginnings of the disease.

Developing technology to help researchers master biology is a huge mission, but Saxonov has enormous confidence that 10x Genomics can accomplish it. “Biology that was mind-bending only recently is now becoming tractable,” Saxonov points out. “The tools we need, we can develop. Now we’re seeing how the pieces are falling into place. I see a future where cancer will be a thing of the past, where Alzheimer’s can be dealt with, and future epidemics will be manageable.”

To make that future a reality, 10x Genomics is investing across its product lines, further advancing Chromium and Visium (its spatial genomics platform) and developing its new in situ platform. “That will take a lot of our investment,” Saxonov remarks, and a long-term commitment.

Saxonov is more interested in building a company that can realize a vision than he is in developing any single product or technology. “We’re sizeable now,” he says, “but very small in terms of where I expect us eventually to be.”

“Biology is the science of this century, like physics was for the 20th century,” Saxonov proclaims. “I see a convergence of fundamental trends—general miniaturization that leads to greater resolution, the maturation of computational technologies, and increasing knowledge of underlying biological processes. We can see exponential progress happening as these areas come together.

“What’s happening now is just the beginning,” Saxonov insists. The mastery of biology will be transformative. 10x Genomics is committed to being a driving force in that transformation.

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