Synthego: On the forefront of genome engineering

Synthego is a virtual laboratory designed to ultimately provide biology as a service, conducting millions of experiments simultaneously. The technological platform not only creates valuable “parts” for biological research, but also enables engineers to construct better tools. By incorporating customer design with product accessibility through an online platform, Synthego is one of a few biotech companies tapping into an unprecedented market, according to CEO Paul Dabrowski.

Started in 2012 by Paul and Michael Dabrowski—both previously SpaceX engineers—Synthego initially hinged on innovating the tools needed to facilitate a scalable, automated system for biology as a service. Eventually, the company transitioned to its current focus, the reagents market.

“We realized that synthetic biology, biotech, and personalized medicine were going to solve the most important problems in the world this coming century,” said Dabrowski. “There’s opportunity, yet the tools that researchers have available are really poor. … Right now, we’re focused … on basically creating kits for CRISPR, because there’s a huge need for better tools and products.”

Interestingly, this is not the first CRISPR kit on the market. One can purchase a kit from The ODIN for bacterial cell engineering. The purpose of the kit The ODIN is selling is to teach the basic molecular biology techniques required for CRISPR, so it is an example experiment. What Synthego is providing is a custom kit to engineer any target sequence in a variety of organisms. It’s more for the industry and academic lab wanting to conduct experiments more quickly and efficiently. Meanwhile, the ODIN is more for the at-home, DIY user learning new techniques. Although the audiences are different, both kits are making CRISPR technology more accessible.

The Synthego CRISPR/Cas9 EZ RNA Kit is designed to provide results to the customer for a specific gene edit. This kit comes in two separate formats, cr:tracrRNA and sgRNA, each relying on a unique and distinct type of synthetic guide RNA. The kit can be purchased with or without Cas9, and is armed with all the ingredients necessary to “transfect, target and edit.”

The synthetic “sgRNA is important because you can really maintain the quality—if you have high quality, input-secure experiments, you get high quality results,” Dabrowski said. “With direct synthesis, and the technology that we created to make that happen, you can have very reliable, repeatable results. We’re talking 90%, sometimes even 100% efficiency.”

This kit will arrive in the mail, along with a protocol card detailing how to actually combine a couple genes together. The customer would then have to use a transfection reagent or perform electroporation to engineer the cell, mammalian or plant. “That’s the general [EZ] workflow—so this can basically be done the same day as you receive your kit. We’re talking about making CRISPR experimentation available within a couple of days.” In addition to these available tools, one can order a Custom RNA kit for varying sgRNA sequence length.

The MVP of these kits, and what Synthego is referring to as CRISPRevolution is the synthetic sgRNA, stabilized sgRNA that is optimum for editing efficiency (CRISPRevolution is a portfolio of synthetic sgRNA, and a hallmark of Synthego). “With synthetic RNA in particular, we’re able to purify to a very high quality, which means that you end up with only one type of molecule in your result—your target molecule.”

This, Dabrowski says, ensures Cas9 is not binding to contaminants, therefore decreasing editing efficiency.

What is evident through these products is Synthego’s brand focus on synthetics; its online accessibility shortens the time it would usually take to produce IVT (in vitro transcribed) or plasmid-derived guides, for instance. The synthetic guide RNA has the potential to render “pre-sgRNA” techniques useless by cutting down the wait time to receive reagents and also enabling precise editing even with more “challenging cell types” where frequent adjustments are essential. According to their team, there are multiple factors that set Synthego apart from competitors who also provide synthetic RNA reagents. One being the “precision, automation and throughput in the synthesis of the synthetic RNA.” The second is increased editing efficiency, resulting from the purity of RNA, with a 90% reduction in off-target editing. And finally, Synthego has reduced the cost by up to five times and shortened the turnaround time to receive reagents by up to four times.

“We wanted to move away from a manual way of doing CRISPR and … [ultimately] provide world-class research tools available to all researchers in molecular biology and biotechnology, that enable rapid, accelerated discovery,” Dabrowski said. “Right now, we are in a situation where the scientists essentially tell us which targets they’re interested in modifying, and we create the kits that enable them to do that modification. So they are doing a decent amount of the design work. In the future, you can envision that we actually take on that responsibility.”

The capabilities of this product, according to Dabrowski, allow CRISPR to be comprehensively and extensively employed. For example, “if you’re trying to modify in another area like personalized medicine, or immunotherapies, you want to modify very hard targets like stem cells. To do so, you need a really high quality, high consistency editing stream. So we’re not only making these research tools accessible, but we’re trying to make it so that there’s even more value to all these downstream applications,” said Dabrowski.

Although the audience of the kits is largely on the applications side, Synthego’s audience dips into no specific scientific discipline, due to the company’s multidisciplinary approach.

“In this field, research is a very interesting term, because it actually spans from academia, all the way through industry, and to the application side. So it’s a worldwide scientific community,” Dabrowski said when asked about the target audience. “We’re seeing various collaborators who are working on immunotherapies to cure cancer; or who are doing research on multiple sclerosis and knocking out the genes associated with that.” Today, Synthego’s audience expands over 50 countries worldwide. “People are finding us all over the world because we have a unique product and it really makes CRISPR much easier,” Dabrowski said.

It is Synthego’s novel synthetic approach to CRISPR reagent synthesis, according to Dabrowski, that distinguishes it from its competitors. Dabrowski and his cofounders built a team of engineers who are enabling the development of better tools. The philosophy they have is to provide a way for researchers to be more productive by focusing on providing the tools and reagents necessary. CRISPR is still in its infancy, and the potentials of the technology are unfolding and evolving; but having cost-effective and efficient tools in place will get us to those potentials more quickly. What they are doing is making CRISPR more accessible by bringing down the cost of these tools, reducing the time it takes to receive them, providing everything necessary to edit your gene of interest, and increasing editing efficiencies.

Having such resources will help revolutionize CRISPR even further and can empower more researchers to advance biological research, extending its reach to every echelon of society.