Most drugs work by changing a conversation between proteins. A hormone binds a receptor, the receptor grabs a partner, and a signal travels through the cell. Yet the standard way to search for new medicines mostly asks a narrower question: does this molecule stick to a target? On November 5, 2026, the Wyss Institute at Harvard announced a platform that asks the better question directly: does this molecule change how two proteins interact?
The platform is called FIND, short for Functional Interaction-based Nanoswitch Discovery. According to the Wyss Institute’s release, it was developed with Boston Children’s Hospital and Harvard Medical School and described in a paper in Science.
The problem with binding-only screens
Many conventional drug screens test compounds one at a time in multi-well plates, with instruments measuring changes in purified proteins or cells. Pooled screens of DNA-encoded compound libraries can search far larger collections, but the Wyss team notes that most such methods only identify molecules that bind to a target. Binding is useful, yet it does not tell you whether a molecule will help or hinder a protein partnership that matters in disease.
That matters because protein-protein interactions sit behind some of the most successful drugs. The release points to examples such as the diabetes drug Ozempic, which mimics the natural GLP-1 hormone and activates its receptor, and inhaled albuterol, which activates beta-2 adrenergic receptors on airway muscle cells so the airways open.
How a DNA nanoswitch works
FIND builds on DNA nanoswitches, programmable devices made from long strands of DNA. Senior author Wesley Wong’s group first developed them for single-molecule measurements and adapted them into a gel assay in 2015. A nanoswitch flips between two shapes: a linear form, in which two attached potential protein partners stay apart, and a looped form, in which the proteins bind and pull two points on the DNA together.
A compound that promotes the interaction increases the fraction of looped nanoswitches. Because looped molecules travel more slowly through a gel than linear ones, standard gel electrophoresis can separate the two groups so each can be collected on its own.
The clever part is the bookkeeping. Each nanoswitch carries one candidate drug molecule on a flexible linker, plus a nucleic acid barcode that identifies it. “Each candidate stays linked to the result of its own experiment,” co-first author Mark Lipstein said in the release. After separating nanoswitches by their response, researchers sequence the barcodes to learn which molecules were selected. Wong summed up the design: build each experiment onto a single DNA molecule so many experiments can run in parallel in one tube.
What the team found
The researchers tested FIND on PPAR-gamma, a diabetes drug target that helps regulate insulin sensitivity and fat storage. Starting from a 400-million-member DNA-encoded small-molecule library, they identified compounds that promoted the receptor’s interaction with a fragment of its partner protein, CBP. Those compounds also increased lipid accumulation in cultured cells, which is consistent with PPAR-gamma activation.
FIND also turned up a nanobody, a small antibody-like protein, that modulated the interaction between the SARS-CoV-2 spike protein and its receptor on human cells. To validate the method, the team recovered a known beta-2 adrenergic receptor activator that had been mixed into a pool of barcoded controls.
These are discovery-stage results. The release describes the molecules as potential starting points for medicines or research tools, not as treatments, and nothing in it suggests they have been tested in patients.
What it means
If the approach holds up across more targets, it could widen the set of biology that drug hunters can reach. “We can directly search for molecules that have the effect we want on a disease-related protein-protein interaction,” said co-first author Clinton Hansen, an instructor at Harvard Medical School. Wyss Founding Director Donald Ingber called it an ultra-high-throughput approach for mechanisms that are currently out of reach for conventional discovery tools.
The technology has already been licensed to a newly formed startup co-founded by members of the research team, a sign that the group sees a path beyond the lab bench. The work was supported by the Wyss Institute, Boston Children’s Hospital, the National Institutes of Health, Takeda Pharmaceuticals and several foundations, according to the release.
For readers following biotech, the takeaway is about method rather than a single drug: screening for function instead of mere binding, at the scale of hundreds of millions of candidates, in one tube.
Conclusion
FIND turns a molecular shape change into a readable signal and a barcode into a record of who caused it. Whether it yields marketed drugs is a question for years of follow-up work, but as a screening idea it is a neat piece of DNA engineering worth watching.