Molecular Interactions Quantified by DNA Nanoswitches (VIDEO)

Professor Wong of the Wyss Institute at Harvard and his team recently published a new study in Nature Methods about using DNA nanostructures to display molecular interactions. Traditionally, bio-molecular interactions are measured through the use of equipment that costs hundreds of thousands of dollars. However, Wong and his group have now developed a method of using gel electrophoresis to determine bio-molecular interactions. Not only has gel electrophoresis been well developed as a technique, but it is also very cheap.

The new part of this technology is attaching molecules of interest onto nanoswitches made of strands of DNA. Interactions between the molecule of interest and another molecule, such as a drug binding to a target receptor, can cause the DNA to change shape from linear to a closed loop. Then, by using gel electrophoresis, researchers can separate and determine the ratio of linear DNA nanoswitches to closed ones. This opening and closing of the loop is essentially measuring the association and dissociation rates of the molecular interactions.

This approach opens doors for scientists all over the world to study, test, and develop new drugs and other biomolecules easily. Wong and his team have created starter-kits to offer to research labs around the world that are interested in using this technology.

a) A nanoswitch functionalized with two digoxigenin molecules and one biotin molecule can adopt 5 discernable states upon addition of a bispecific receptor. All 5 topological states, A-E, can be resolved within a single lane of an agarose gel. These bands can be fit globally with a single fit of a sum of skewed Gaussian curves. The black curve represents the median pixel intensity, the dashed red curve represents the fit which is the sum of 5 skewed Gaussians, and the individual skewed Gaussians are shaded by state. b) A reaction diagram illustrating the possible transitions between each of the 5 states. c) (left) on-rate measurements indicating the value of each state at 20 different time points. Solid curves indicate the result of a global fit of all states to the kinetic model illustrated in c. (right) off-rate measurements indicating the value of each state at 12 different time points. Solid curves indicate the result of a global fit of all states to the kinetic model illustrated in b. These fits taken together allowed for the determination of all rate constants from 32 lanes which can be run on a single gel.

From the Wyss Institute press statement:

“Wesley and his team are committed to making an impact on the way bio–molecular 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, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Boston Children’s Hospital and Harvard Medical School and a Professor of Bioengineering at Harvard SEAS. “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.”

Wyss Institute: DNA Nanoswitches Reveal How Life’s Molecules Connect…

Study in Nature Methods: DNA Nanoswitches: A Quantitative Platform for Gel-Based Biomolecular Interaction Analysis…