In their publication, Encapsulation of Gold Nanoparticles in a DNA Origami Cage, Zhao Zhao, Erica Jacovetty, Yan Liu, and Hao Yan demonstrate how to create a rectangular box with a cavity using the bottom-up self-assembly properties of DNA origami. In this particular study, this structure is used to encapsulate gold nanoparticles in order to be able to tag the surface of the nanoparticles with a a controlled number of unique molecules and to control the orientation and intermolecular distance between the nanoparticles. A significant advantage to the DNA origami method is the 6nm spatial resolution that can be obtained with binding sites. This structure exhibits a relatively high folding yield and was also found to be fairly robust, withstanding moderate mechanical strain from large nanoparticles placed in the cavity.
Beyond this particular structure, DNA origami has a number of inherent advantages over other types of nanoparticles used for similar drug delivery applications. Currently there exists no equivalent technology capable of making a seemingly infinite number of arbitrary shapes like one can with DNA nanotechnology. Additionally, the surfaces of these structures can be functionalized simply by extending oligonucleotides and capping the oligonucleotides with a complimentary sequence bound to a functional polymer.
With an increasing number of neurological questions still requiring answers, one prominent barrier that remains is a difficulty transporting drugs across the blood-brain-barrier. Creating a vehicle capable of delivering drugs to the brain, concentrating the biodistribution almost entirely to the brain, would be an extremely valuable tool towards advancing treatment for neurological diseases. Additionally, it still is very difficult to study neuronal activity in the brains of monkeys and humans. When working with mice and rats, there exists a wide variety of recording equipment that can be inserted in the brain with ease. If these particles can be delivered to the brain with ease, they can also be packaged with entities that can record or stimulate neurons.
The aim of our project is to develop a general strategy to functionalize DNA structures with bioactive cues, namely peptides.
We will demonstrate the utility of this approach with two applications. First, we will attempt to get structures into cells in an organized and controlled fashion, and second, get structures to pass through the blood-brain-barrier and enter the brain through the bloodstream.
Oligonucleotides are extended from the two ends of the box perpendicular to the plane of the cavity.
Once the crude folded structure has been purified to remove stables and misfolded structures, a synthesized carrier polymer can be attached to a complimentary capping sequence that will bind to the extended ends to create functional sites at each extended helix.
Peptides will then be attached to the carrier polymers and the functionalization process will then be complete.
1. Modify the original literature box with extended ends.
2. Cap the extended ends with a fluorophore to verify functionalization capabilty.
3. Make the polymer for functionalization and verify binding.
3. Scale up products.4. Test in cells and mice and compare to control.