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DNA Nanostructures for Drug Delivery

Customizable nanostructures can be built using DNA

Researchers at the Wyss Institute have developed two methods for building arbitrarily shaped nanostructures using DNA, with a focus on translating the technology towards nanofabrication and drug delivery applications.

One proprietary nanofabrication technique, called “DNA-brick self-assembly,” uses short, synthetic strands of DNA that work like interlocking Lego® bricks. It capitalizes on the ability to program DNA to form into predesigned shapes thanks to the underlying “recipe” of DNA base pairs: A (adenosine) only binds to T (thymine) and C (cytosine) only binds to G (guanine).

Gallery of nanoscale three-dimensional shapes built by programmable self-assembly from DNA. Each cylinder represents one double helix, 2 nm in diameter. Credit: Wyss Institute at Harvard University.

The second DNA nanofabrication method being developed at the Wyss Institute is known as DNA origami. Using the principle of programmable self-assembly, strands of DNA are directed to form custom, specific shapes of tightly cross-linked double helices. One long single strand of DNA is used as a ‘scaffold,’ which is manipulated to form a lattice through base-pairing with numerous short, chemically-synthesized DNA strands that are specially designed using computer software. In this manner, DNA origami is now being used to create 3D structures, with the goal of building nanoscale tools and drug delivery devices.

The combination of DNA nanostructures’ ability to be accurately patterned at the nanoscale, its simplicity in being pre-programmed for rapid assembly within hours, and its capability to integrate thousands of DNA components into complex architectures all make it an attractive method for nanofabrication.

We are moving at lightning speed in our ability to devise ever more powerful ways to use biocompatible DNA molecules as structural building blocks for nanotechnology

Donald Ingber

DNA nanostructures are excellently poised to deliver therapeutics in a programmable way. Wyss researchers have found a way to protect DNA structures from in vivo degradation and to design and fabricate drug capsules utilizing programmable spatial control of drug receptors.

The nanofabrication technique, called “DNA-brick self-assembly,” uses short, synthetic strands of DNA that work like interlocking Lego® bricks. It capitalizes on the ability to program DNA to form into predesigned shapes thanks to the underlying “recipe” of DNA base pairs. This animation accurately shows how the DNA strands self assemble to build a structure.

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