(Christian Guthier, Flickr. https://flic.kr/p/4adoJP)
4 Apr. 2023. A life science venture investor is funding further development of a lower-cost molecular-level drug discovery process using nanoscale synthetic DNA strands. Northpond Ventures in Cambridge, Massachusetts is backing the DNA nanoswitch project for screening small molecule and biologic drug candidates, at the Wyss Institute for Biologically Inspired Engineering, a research center at Harvard University.
DNA nanoswitching aims to provide a straightforward technique for documenting and measuring the simultaneous interactions of chemical compounds or biological drug candidates on molecular targets. The technology, called “lab-on-a-molecule” at Wyss Institute, is based on research in the lab of Wesley Wong, professor of biochemistry and molecular pharmacology at Harvard Medical School and Boston Children’s Hospital. Wong is also an associate faculty member at Wyss Institute.
While many academic and industry teams are investigating new drug discovery techniques, Wong and colleagues are seeking simpler and less expensive methods for understanding the complex interactions between chemicals or biologics on molecular targets. The DNA nanoswitch technology starts with a strand of synthetic DNA that acts as framework to chemically attach molecules for testing on drug targets. As the DNA strand laden with test molecules interacts with the target, the strand changes shape, for example from an open strand to a loop. Wong’s lab says these changes in state, or switches, in DNA strands, can be captured and measured with readily available lab reagents and instruments.
In Oct. 2021, Wong and colleagues published a paper demonstrating DNA nanoswitching with force spectroscopy, a commercially available lab instrument, to measure multiple precise coordinates of single-protein molecules. These measurements, say the researchers, make possible unique identification of individual molecules such as DNA and peptides with atomic granularity, as well as calculating their volumes in mixed samples.
Screen entire candidate libraries
In Sept. 2022, Wyss Institute identified DNA switching, now called lab-on-a-molecule, as a validation project, its program to advance promising technologies into commercialization, addressing questions of marketability and reducing risks to investors. The institute says lab-on-a-molecule can be used to screen entire libraries of small molecules, peptides, or biologics against targets to find proof-of-concept therapy candidates to treat a wide range of diseases.
In 2020, Wyss Institute and Northpond Ventures formed Northpond Labs, with the company providing $12 million over five years to support emerging technologies in Wyss-affiliated labs having commercial potential. Lab-on-a-molecule is the third and latest of these technologies to receive Northpond Labs funding. Science & Enterprise reported in the past year on the first two Northpond Labs recipients: research to improve the reach and targeting of cell therapies to more diseases and a more efficient process for making synthetic RNA molecules.
Wong plans to apply Northpond’s support to extend the technology into discovery of molecules with specific therapeutic properties. “We are developing a next-generation platform for compound screening that uses self-assembled nanodevices to accelerate the discovery process,” says Wong in a Wyss Institute statement. “With support from Northpond Labs we hope to find novel activators for multiple different conditions, including therapeutics such as allosteric regulators and molecular glues.”
“While there are many tools for disrupting protein-protein interactions, there remains an unmet need to interrogate at scale, molecules that promote these interactions,” adds Northpond Ventures founder and CEO Michael Rubin. “Lab-on-a-molecule is suited for this purpose, and we believe it can be applied across research and therapeutics development.”
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