May 15, 2017 (Vol. 37, No. 10)
Synthetic RNA: One Small Step for Synthego, One Giant Leap for Biology as a Service
Synthego is applying the Agile development methods and entrepreneurial lessons its founders learned at SpaceX to biotech, with the eventual goal of developing a virtual cloud laboratory offering biology as a service. Its flagship product, CRISPRevolution, is the first step. It streamlines gene editing so that even researchers new to the techniques can succeed.
“CRISPRevolution is a family of kits, custom libraries, and other products in the genome engineering space,” co-founder and CEO Paul Dabrowski says. “It includes the world’s first synthetic single guide RNA kit for CRISPR genome engineering.”
The ability to manipulate RNA is one of the key components of the genome engineering workflow, but creating RNA in the laboratory is traditionally difficult. Synthetic RNA can shave as much as one week off CRISPR experiments, eliminating the need to design, construct, and verify sequences, and avoiding the purification of plasmid or in vitro-transcribed RNA.
Synthego’s synthetic RNA is completely free of DNA and “allows scientists to manipulate the cell much better,” Dabrowski notes. It offers up to 90% knockout efficiency.
“The quality of our RNA is higher than scientists typically can create in the field, so high-fidelity editing is possible,” he continues. “Because the CRISPR functions can be more precise, cells can be modified more quickly than with other methods. For example, CRISPRevolution enables results to be generated in a couple of days rather than in a couple of weeks.”
Some of the speed emanates from simplifying the validation process. Although validation is still required, CRISPRevolution modifies 80–90% of the cells correctly versus about 10–30% of those created by older technologies. Scientists, therefore, are more likely to successfully validate edited cells each time.
Synthego’s CRISPRevolution is a portfolio of synthetic RNA designed for CRISPR genome editing and research. The company’s offerings include sgRNA kits, cr:tracrRNA kits, and custom and modified RNA. According to Synthego, the benefits of synthetic RNA over plasmid-derived or in vitro-transcribed guides include faster transfection readiness, greater accuracy and consistency, less laboratory time, and lower labor costs.
The Future of CRISPR Research
Synthego’s 2017 Future of CRISPR Research report indicates that 87% of new CRISPR users are also new to gene editing. “That’s both surprising and telling,” remarks Sam Liu, Synthego’s vice president of commercial marketing. “It shows the appeal and power of CRISPR, which brings new scientists into gene editing and increases the population of researchers.” Those researchers will require a new generation of tools that streamline the work, thereby delivering results faster and more efficiently.
Dabrowski and Liu say it’s too early to discuss new products in development, but Synthego’s team is addressing challenges in efficiency, verification of edits, and delivery/transfection—the top three pain points in gene editing. “We want world-class tools for all researchers,” Dabrowski emphasizes.
The patent lawsuits surrounding CRISPR haven’t affected Synthego. “Our technology is focused on the basic hardware and software to run the scientific workflow related to gene editing,” Dabrowski insists. “We’re closely engaged with all the players in CRISPR’s development, and they see these kits as adding value to their intellectual property flow.”
SpaceX Methods Port to Biotech
Synthego founders Paul and Michael Dabrowski were once engineers at SpaceX. That experience introduced the brothers to an innovative, entrepreneurial culture based on Agile methodology and agile thinking. Agile development methods are based on close collaboration among stakeholders to develop projects in smaller, iterative steps—typically every few weeks. Consequently, missteps are minimized because course corrections are made throughout development.
That was perfect for SpaceX and its grand vision to help colonize Mars. SpaceX engineers realized that rapid iteration could make a huge impact. “The ability to write and test code within hours was important, so SpaceX manufacturing and testing engineers work at one site,” Dabrowski details. “That proximity helps ensure that iterative tests occur within days rather than weeks.”
The concept of scalability also was powerful. “Inspired by the impact of Moore’s law and scalability in computers, SpaceX automated as much of the manufacturing process as it could,” adds Dabrowski. “That enables it to produce up to a dozen rockets per year in one-tenth of the space required by its competitors.”
Those same concepts of iterative development and scalability form the basis of Synthego.
Agile Biotech
Paul and Michael Dabrowski eventually left Aerospace for Biotech, realizing this field holds incredible opportunities in terms of curing diseases, feeding the world’s population, and solving seemingly intractable energy problems. They brought the Agile mindset with them.
“Scientists in their labs don’t get the support they need,” Dabrowski says. “They have laboratory equipment, but they have to do much of the work manually themselves. That gets in the way of an Agile process.”
Synthego brings Agile concepts to bear on researchers’ workflows through automation and scalability. “We spent about four years developing the core technology for hardware and software to make genome engineering processes better,” Dabrowski says.
Cross-Disciplinary Team
Synthego is comprised of a variety of disciplines beyond those usually found in biotech companies. In addition to biotech industry professionals, it boasts a broad mix of staffers with backgrounds in engineering, technology, and math, as well as operations and manufacturing. “The cross-disciplinary blend of software, hardware, chemistry, and biology is tightly coupled here. Our team adheres to engineering values,” Dabrowski says. In other words, the company has an iterative, Agile mindset.
The company’s flagship product, CRISPRevolution, was officially released in August 2016. In the future, Synthego foresees a virtual cloud laboratory or biology as a service—familiar concepts in the computing world—that will allow researchers to program a set of experiments that would occur in a Synthego facility.
Right now, Dabrowski says, “We want to continue improving the workflow and simplifying the science. We’re focusing on automating physical research … to turn biology into information science.”
Synthego
Location: 3696 Haven Avenue, Redwood City, CA 94063
Phone: (650) 206-4011
Website: www.synthego.com
Principal: Paul Dabrowski, CEO
Number of Employees: 50
Focus: Synthego develops synthetic RNA products for CRISPR genome editing. These products are designed to facilitate automated workflows, improve editing efficiency, and reduce off-target effects.
