DNA Nanobox: A Self-Assembling Nanoscale Container for Drug Delivery

This is one of the projects submitted by Harvard’s team at the 2006 iGEM competition (see here and here for our recent posts about this year’s iGEM).
Some of the bullet points about the project:

Project Overview

Traditional drug delivery is fairly low-tech. Tablets containing a mixture of active small molecules and binders are ingested, and the small molecules circulate non-specifically throughout the body. Even when a specific cell or tissue type is targeted (e.g. cancerous cells or bacterial infections), many other tissues are exposed to the drugs, often with serious side effects. We envision a future in which medicines will be delivered in a highly specific manner to targeted tissues and cell types, and set out to make initial steps toward realizing this vision.

Our goal for the summer was to design and implement nanoscale molecular containers, which could be dynamically opened and closed by an external stimulus. This is the first step to making more sophisticated drug-delivery vehicles.

The containers were implemented as DNA nanostructures, which afford a significant degree of positional control and chemical versatility.

To demonstrate that our designs successfully self-assembled, we used negative-stain electron microscopy to visualize the containers.

As an initial proof-of-concept, we planned to demonstrate that our DNA containers could be used to “protect” biotinylated oligonucleotides from binding by streptavidin-coated magnetic beads.

We were able to successfully show that nanoboxes with internal biotinylated oligonucleotides did not bind to streptavidin-coated magnetic beads, while nanoboxes that were externally decorated with biotinylated oligonucleotides were bound by the same beads.

Results

The following images show our most successful container design, both as a 3D cartoon and in actual negative-stain EM images. The outer length, width, and depth of this container design is approximately 30x30x30 nanometers, so it is bigger than a typical ribosome. The inner diameter of the container is approximately 12 nanometers.

The basic design of this container is a hexagonal barrel, closed off by two flat lids.

MIT’s Tech Review has an interview with the Harvard team (key quote: “We know DNA is a very stable building material… Now we’re trying to take advantage of the fact that it’s programmable.”) Read the full article here…
Harvard’s 2006 iGEM team page…
Project details…