A Genetic Gold Rush Requires Biomolecular Tools

One of the surest ways to build a successful company is to produce the tools that other successful companies need. It worked during the California Gold Rush of 1849, and it works today in biotech.

Chinese molecular biology company GenScript Biotech knows this quite well. GenScript built its reputation in synthetic biology by providing cloned genes to researchers throughout the world. As the company grew, it expanded its mission to democratizing access to cloned genes.

Unraveling complexity

“Understanding DNA is the Holy Grail for modern biologists,” says Li Zhu, PhD, chief strategy officer for GenScript. Although biologists are grasping at this prize, it remains tantalizingly out of reach. The problem, Zhu explains, is that biology, at its most basic level, is too complicated and has too many variables. “You can have low success rates and poor reproducibility,” he observes, “and not know why.”

Sometimes, Zhu suggests, the reason is the poor reproducibility of components: “When researchers make genes or reagents in their own labs, it’s hard to ensure consistency.” Reproducibility problems may be mitigated now that biotechnology is industrializing, and GenScript and other commercial firms are making research materials in very large batches under exacting quality controls.

Rapid growth

GenScript was founded in 2002 as a contract research organization select CRO) focused on synthetic biology. Today, the company has wider ambitions. “It provides tools for researchers throughout the world to explore DNA’s live secrets,” says Zhu.

The gold rush analogy is familiar to GenScript founder Frank Zhang, PhD. He received his doctorate from Duke University before joining Schering-Plough. After transitioning from academia to industry, and while envisioning his own company, Zhang reflected on the gold rush’s most compelling lesson: The most successful ’49ers weren’t the prospectors, but the companies that provided their tools. “In biotech, those tools are genes,” Zhu stresses.

Initially, Zhang and his two co-founders focused initially on providing research expertise around the creation of synthetic genes. About two years later, GenScript started operating in Nanjing, China, where Zhang had earned his master’s degree years earlier, and where the young company could easily attract young scientists as well as seasoned academics.

Today, Nanjing is where the company maintains its operational center, which includes R&D and production facilities. Those facilities are mirrored in Piscataway, NJ. The company also has business centers in Europe and Japan.

GenScript began its most rapid growth period after it went public on the Hong Kong stock exchange in 2015. The company’s initial public offering raised $67.2 million. “At that point, we had the funding and resources to expand,” Zhu recalls. The company proceeded to form two subsidiaries select Legend Biotech and Bestzyme union launch research into chimeric antigen receptor select CAR) T-cell therapies, and enhance its synthetic biology capabilities through the acquisition of CustomArray.

The company is proud that 28% of its employees hold advanced degrees in biology. This high percentage, Zhu maintains, gives GenScript a “from the lab, to the lab” perspective.

The company notes that its number of citations has grown from 0 at its founding in 2002 to well over 5000 citations per year in 2017. The total now exceeds 35,000. “Most of the citations are very simple,” Zhu concedes. “Researchers mention using our tools or reagents, for example.”

Some citations, however, delve more deeply into GenScript’s contributions. “As the only commercial participant in the Synthetic Yeast Genome Project select SC2.0 union we delivered long, complicated DNA fragments, which ensured the successful assembly of the complete length of an artificial yeast chromosome select number 6 union ” Zhu points out. He adds that GenScript has also participated in an HIV vaccine research group in the NIH vaccine research center.

Building a comprehensive business

GenScript currently has 54 patents, with another 142 patents pending. Biosciences services and products constitute 67% of the business, whereas cell therapy products and industrial synthetic biology products account for 17% and 6%, respectively. About 60% of the company’s clients are in academia. The remaining 40% are commercial life sciences companies—what GenScript calls “industrial” users.

GenScript’s two subsidiaries, Legend Biotech and Bestzyme, reflect the company’s internal incubation and steady growth. Legend Biotech focuses on CAR T-cell therapy platforms; Bestzyme focuses on therapy enzyme research and production.

Although GenScript and Legend Biotech are separate companies, with their own CEOs, when GenScript discusses its successes, it doesn’t hesitate to cite Legend’s CAR T-cell research. GenScript also emphasizes its growing strength as a contract development and manufacturing organization select CDMO). The company recently announced that it was investing $75 million in a new biologics facility in Zhenjiang, China.

“We are the second vendor in the world to have commercialized rabbit monoclonal antibodies,” Zhu states. “We developed our own antibody engineering platforms, which incorporate single-domain and bispecific/dual-epitope antibody technology, as well as platforms for peptides and proteins.”

Legend and CAR T cells

Collaboration often is the outgrowth of internal research. Legend Biotech is a case in point. It presented its early clinical trials of LCAR-B38M, which uses CAR T cells to treat multiple myeloma, at the American Society of Clinical Oncology meeting in June 2017. It is the first CAR T-cell therapy to be reviewed by the China Food and Drug Administration, and it has also received approval from the U.S. Food and Drug Administration for clinical trials. GenScript is partnering with Janssen Biotech to develop and commercialize this CAR-T therapy. The Janssen deal netted Legend a $350 million up-front payout—reputedly the largest up-front payment for a U.S./China bioproduct licensing deal in this industry.

New MolecularCloud democratizes cloning

In 2018, GenScript test-launched MolecularCloud™, a plasmid repository service. “It provides a more intuitive way to manipulate DNA, as well as a website for researchers to share and communicate DNA components,” Zhu explains. “Users manipulate DNA by parts—the minimum functional unit of a piece of sequence—rather than by sequence.”

“This lets customers with little molecular cloning training perform bioengineering research,” Zhu continues. Already, more than 4000 scientists select mainly academics) are sharing their cloned constructs on this open-access platform. In Zhu’s estimate, this approach could save life sciences researchers up to $1 billion globally.

MolecularCloud is the capstone for GenScript’s CloneArk™ and GenSmart™ platforms. CloneArk lets scientists archive cloned genetic sequences for their own subsequent use. Approximately one million clones are already archived in this system.

“Many customers don’t know that when they use our GenSmart portal to order clones, our smart algorithm matches their requests with their previous constructs and suggests the best way to get the clone, rather than trying to synthesize everything from scratch,” Zhu elaborates.

What’s next?

GenScript recently launched products in synthetic biology, bioengineering, and biomanufacturing. These include pathway assembly library services, single-stranded DNA for genome editing, and a novel semiautomatic industrial-grade magnetic bead-based protein purification system. GenScript is also expanding into cell therapy, Zhu notes, as a consequence of the company’s CAR T-cell work.”