In the world of structural biology, few tools have had as profound an impact as scFv16. This single-chain variable fragment antibody has revolutionized the study of active G protein-coupled receptors (GPCRs), enabling researchers to determine the structures of hundreds of these crucial proteins. By stabilizing GPCR/G-protein complexes, scFv16 has made it possible to solve these structures routinely using cryo-electron microscopy (cryo-EM)—a task that was once nearly impossible due to the instability and small size of the complexes. At the time of writing, nearly 500 GPCR structures stabilized with scFv16 have been deposited, with many more unpublished ones held under wraps in industry, underscoring the widespread adoption of this tool.

"Tools for stabilisation of GPCR-G protein complexes are critically important for structure determination. scFv16 has had a major impact on GPCR structure determination and discovery sciences due to its broad utility across multiple G protein subfamilies and it is routinely used for structure determination in Academia and Industry. By making scFv16 license free and open access, the discoverers have greatly advanced the field and the potential of structure-based drug discovery for GPCRs," said Prof. Patrick Sexton, a GPCR cryo-EM pioneer at Monash University.

Yet, what’s lesser known about scFv16 is the story of its origins. In a field where many enabling technologies are patented and tightly controlled, Roche, the pharmaceutical company behind scFv16, made a remarkable decision: they chose not to patent it. Instead, they gifted this transformative tool to the scientific community, allowing researchers and companies worldwide to use it freely.

This choice has had a profound ripple effect. Laboratories across the globe, including Proteros, a leading structural biology service provider, also uses scFv16 to stabilize some GPCR complexes and accelerate drug discovery efforts.

"scFv16 has allowed us to deliver high-quality GPCR structures faster and more efficiently to our clients," said Stephan Krapp, Business Unit Head for Structural Biology at Proteros. "It’s truly indispensable."

The Visionaries at Roche: A Gift to Science

Behind scFv16 are the unsung heroes at Roche, whose foresight and generosity have driven breakthroughs in GPCR research. Their decision to keep scFv16 open-access wasn’t about profit—it was about advancing science.

"We knew scFv16 has the potential to enable critical research across the field," shared Roger Dawson, the project leader responsible for scFv16's discovery at Roche. "By choosing to make scFv16 open source, we aimed to advance the GPCR field, structural biology, and, more importantly, speed up the development of better treatments for severe diseases. One of our key aspirations was also to promote the use of cryo-EM for structure-based drug design (SBDD), which was still in its infancy at the time. We wanted to give it a push for everyone’s benefit.”

Shoji Maeda, then Roche postdoctoral fellow at the Paul Scherrer Institute who developed scFv16, echoed this sentiment, adding, "This molecule was truly a collaborative effort with Roche scientists with whom we share passion and expertise. We are fortunate to have exceptional scientists in the GPCR community who drive the research using various tools, and it is remarkable that scFv16 has been playing an instrumental role in accelerating the structural biology of GPCR. We are incredibly proud of making this tool public.”

A Lasting Legacy

Today, scFv16 continues to be a cornerstone in GPCR structural biology, helping researchers unlock insights into these essential proteins. Roche’s decision to share this tool freely has empowered countless discoveries, proving that sometimes, the greatest advancements come from a spirit of generosity.
As scFv16 remains a vital tool in labs like Proteros, we celebrate not just the technology, but the unsung heroes who made it possible. Their decision to give back to the community will fuel scientific breakthroughs for years to come.