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Behavior of life's molecules revealed

New “DNA nanoswitches” can detect molecular activity for pennies per sample

Video: Wyss Institute at Harvard

A complex interplay of molecular components governs almost all aspects of biological sciences—healthy organism development, disease progression and drug efficacy are all dependent on the way life’s molecules interact in the body. Understanding these biomolecular interactions is critical for the discovery of new and more effective therapeutics and diagnostics to treat cancer and other diseases, but currently this requires scientists to have access to expensive and elaborate laboratory equipment.

Now, a new approach developed by researchers at Harvard Medical School, the Wyss Institute for Biologically Inspired Engineering at Harvard and Boston Children’s Hospital promises a much faster and more affordable way to examine biomolecular behavior, opening the door for scientists in virtually any laboratory worldwide to join the quest for creating better drugs. The findings are published in February’s issue of Nature Methods.

“Biomolecular interaction analysis, a cornerstone of biomedical research, is traditionally accomplished using equipment that can cost hundreds of thousands of dollars,” said Wesley P. Wong, HMS assistant professor of biological chemistry and molecular pharmacology at Boston Children’s Hospital, associate faculty member at the Wyss and senior author of study. “Rather than develop a new instrument, we’ve created a nanoscale tool made from strands of DNA that can detect and report how molecules behave, enabling biological measurements to be made by almost anyone using only common and inexpensive laboratory reagents.”

Wong calls these new tools DNA “nanoswitches.”

Nanoswitches comprise strands of DNA onto which molecules of interest can be strategically attached at various locations along the strands. Interactions between these molecules, such as successful binding of a drug compound with its intended target—a protein receptor on a cancer cell, for example—cause the shape of the DNA strand to change from an open and linear shape to a closed loop. Wong and his team can easily separate and measure the ratio of open DNA nanoswitches vs. their closed counterparts through gel electrophoresis, a simple lab procedure already in use in most laboratories, which uses electrical currents to push DNA strands through small pores in a gel, sorting them based on their shape.

“Our DNA nanoswitches dramatically lower barriers to making traditionally complex measurements,” said co-first author Ken Halvorsen, formerly of the Wyss and currently a scientist at the RNA Institute at the University at Albany. “All of these supplies are commonly available and the experiments can be performed for pennies per sample, which is a staggering comparison to the cost of conventional equipment used to test biomolecular interactions.”

To encourage adoption of this method, Wong and his team are offering free materials to colleagues who would like to try using their DNA nanoswitches. 

“We’ve not only created starter kits but have outlined a step-by-step protocol to allow others to immediately implement this method for research in their own labs or classrooms,” said co-first author Mounir Koussa, a PhD candidate in neurobiology at HMS.

“Wesley and his team are committed to making an impact on the way biomolecular research is done at a fundamental level, as is evidenced by their efforts to make this technology accessible to labs everywhere,” said Wyss Institute Founding Director Donald Ingber, who is also the HMS Judah Folkman Professor of Vascular Biology at Boston Children’s. “Biomedical researchers all over the world can start using this new method right away to investigate how biological compounds interact with their targets, using commonly available supplies at very low cost.”

Anyone interested in learning more about how to use DNA nanoswitches in their lab can watch a protocol video series and request free materials for making them at wyss.harvard.edu/nanoswitch.

Adapted from a news release written by Kat J. McAlpine, Wyss Institute at Harvard.