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Revision as of 11:00, 12 October 2013
Boston University
BIOMOD 2013 Design Competition
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Design Goals
Problem
With an increasing number of unanswered questions in neuroscience, one prominent barrier has been a difficulty in transporting drugs across the blood-brain-barrier. Creating a vehicle capable of delivering drugs to the brain, concentrating the biodistribution within 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.
Solution
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.
We will begin with the rectangular box with the cavity, described by Zhao et al. in Encapsulation of Gold Nanoparticles in a DNA Origami Cage.
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.
Project Goals
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.
