Computer models the most complex 3D DNA shapes

Date: Dec-04-2014 A new computer model that allows biological engineers to design the most complex

3D DNA structures ever made takes 3D DNA origami to a new level. The

advance could help scientists probe some of the tiniest processes of biology - such as

photosynthesis. It could also help create new types of drugs or RNA therapies - an

emerging frontier of personalized treatment for diseases like cancer.

The computer model allows biological

engineers to exercise nanometer-scale control to build complex 3D DNA shapes.
Image

credits: Top row - Stavros Gaitanaros (MIT) & Fei Zhang (Arizona State

University); Bottom row - Keyao Pan (MIT) & Nature Communications

In the journal Nature Communications, a team of researchers, including

members from the Massachusetts Institute of Technology (MIT), describe how they designed the

computer model and used it create elaborate 3D DNA shapes, including rings, bowls and

icosahedrons that have structures similar to viruses.

As scientists get better and better at probing and manipulating matter at the scale of

individual atoms and within molecules - the realm of nanotechnology - so grow the

opportunities for biological engineers to use DNA as a nanoscale building material.

DNA is stable, and scientists can easily program it by changing the sequence of its

building blocks. But the function of DNA relies not only on the sequences of its chemical

subunits, but also on its shape. So, about 10 years ago, scientists started manipulating

DNA in two dimensions - and gave rise to the term "DNA origami."

The 2D DNA shapes were made by binding "staple strands" to "DNA scaffolds." Later,

scientists combined this method with nanotechnology and began to work with 3D DNA origami. This led to suggestions that 3D DNA

nanostructures could one day be used to deliver drugs, act as biosensors, perform

artificial photosynthesis and more.

The more complex the structure that can be designed, the more promising the range of

applications that the technology offers. With this latest model, for example, the MIT-led

team believes researchers will be able to build DNA scaffolds that anchor arrays of

proteins to build new vehicles for RNA therapies and chromophores or light-sensitive

molecules to mimic plant photosynthesis.

New model uses 'precise nanometer-scale control' to make 3D DNA shapes

Senior author Mark Bathe, an associate professor of biological engineering at MIT,

explains the step forward that their study represents in the field of 3D DNA

origami:

"The general idea is to spatially organize proteins, chromophores, RNAs and

nanoparticles with nanometer-scale precision using DNA. The precise nanometer-scale

control that we have over 3D architecture is what is centrally unique in this

approach."

The progress toward the new model has been slow and painstaking. In 2011, the team

developed a model called CanDo to create 3D DNA shapes - but it could only make a

limited range based on rectangular or hexagonal close-packed lattices of DNA bundles.

This latest version uses a new algorithm that helps the team create much more complex

structures than were previously possible. It can take sequences of DNA scaffold and

staple strands and predict the 3D structure of virtually any programmed DNA

sequences.

Prof. Bathe says predicting the 3D structure in the model "is central to diverse

functional applications we're pursuing, since ultimately it is 3D structure that gives

rise to function, not DNA sequence alone."

Model cuts DNA sequences into 'multiway junctions'

The new model works by cutting DNA sequences into subunits called "multiway junctions"

- essential building blocks of programmed DNA nanostructures, similar to those that form

naturally during DNA replication. Multiway junctions are what allow DNA strands to cross

over and bind to the strand of an adjacent DNA helix when they unwind and form new pairs during

replication.

The computer model then re-assembles the cut-up DNA into larger programmed, nanoscale

shapes such as rings, discs and spherical containers. Re-programming the sequences of

these components allows DNA origami designers to easily create complex architectures,

including symmetrical cages shaped like tetrahedrons, octahedrons and dodecahedrons.

Prof. Bathe explains that the 3D DNA shapes are just "passive scaffolds." Their

function comes from the other molecules that can be attached to them and provide a range

of applications.

One example the team is working on is trying to mimic the protein scaffold structure

that allows living plant cells to carry out photosynthesis. Protein scaffolds are harder

to engineer into nanoscale assemblies - so the 3D DNA origami method provides a useful

alternative. The scientists can attach chromophores to the DNA scaffold instead, in order to

create the key structures for photosynthesis.

The video from MIT below further explains how the new model works:

DNA scaffolds can carry drugs into cells 'without setting off alarms'

Other applications are also possible - such as scaffolds that allow scientists to

mimic bacterial toxins so they can create versions that are non-toxic that they can use

to deliver RNA therapies directly into cells.

Using DNA scaffolds to carry therapeutics like microRNAs, mRNAs and cancer drugs, it is

possible to get into cells without setting off a lot of alarms or degrading the cell

machinery, Prof. Bathe explains.

The team plans to make their algorithm publicly available so other DNA designers can

use it. They first want to improve the model so designers can simply give it a specific

shape and obtain the sequence that will produce that shape.

Such an enhancement would enable true nanometer-scale 3D printing, where the "ink" is

synthetic DNA, says the team.

Funds for the study came from the Office of Naval Research and the National Science

Foundation.

Written by Catharine Paddock PhD

Not to be reproduced without permission.

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Courtesy: Medical News Today Note: Any medical information available in this news section is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional.