A Q&A on designing DNA nanostructures for biomedical purposes

By discovering new methods to govern matter on the atomic and molecular ranges, advances in nanotechnology are paving the way in which for improvements in drugs, electronics, supplies science and environmental remediation, amongst many different areas.

An necessary specialty on this subject—and a signature space of examine on the College at Albany’s RNA Institute—is DNA nanotechnology, whereby the bottom pairs that comprise DNA molecules are manipulated to construct tiny constructions in numerous shapes that can be utilized for purposes together with drug supply, medical diagnostics and even information storage.

RNA Institute researchers together with Postdoctoral Fellow Bharath Raj Madhanagopal and Senior Analysis Scientist Arun Richard Chandrasekaran, along with a crew of UAlbany collaborators, coauthored a brand new examine that explored the distinctive properties of a sure type of DNA nanostructure known as “switchback DNA” that would have implications for DNA folding in nature and be helpful in designing new forms of nanostructures with biomedical purposes.

Their findings have been revealed in Nature Communications.

Right here, Madhanagopal and Chandrasekaran share insights on the basics of their subject and the advances that lie in wait with new discoveries in DNA nanotechnology.

What are DNA nanostructures, and why are they necessary?

Many know DNA because the molecule that shops the genetic info that’s handed from one era to the following. The chemical properties of DNA that make it a superb molecule for storing genetic info additionally make it a helpful development materials—particularly relating to making tiny objects, as small as just a few nanometers.

The sequences of the 4 nucleobases in DNA—adenine, guanine, thymine, and cytosine –are inherently programmable. It’s because adenine at all times pairs with thymine, and guanine with cytosine. These dependable patterns in base pairing permit us to design particular strands of DNA that bind collectively like Lego blocks to type nanostructures.

Through the use of DNA to construct nanostructures, we will obtain wonderful precision within the measurement of the constructions. We are able to additionally make objects of numerous shapes and architectural intricacies—capabilities that aren’t simply achieved utilizing different applied sciences. DNA nanostructures at the moment are being developed to be used in drug supply, diagnostics, and information storage, to call just a few purposes.

What’s ‘switchback DNA?’

Simply as we use bricks to assemble buildings, we use nanometer-sized constructing blocks known as “motifs” and “tiles” manufactured from DNA to create elaborate constructions in DNA nanotechnology. Just like how bricks can come in numerous sizes and styles, so can motifs and tiles. Creating these structural motifs and understanding their properties is the muse of DNA nanotechnology analysis.

“Switchback DNA” is likely one of the earliest DNA motifs designed by Nadrian Seeman, the founding father of the sphere of DNA nanotechnology. We needed to discover how its curious structural options would manifest in nanostructures. By learning the properties of switchback DNA, we consider we will create much more numerous DNA-based nano-objects with unique properties.

What makes switchback DNA distinctive?

Switchback DNA has solely two strands, so it may be immediately in contrast with the double helical construction of DNA that everybody is accustomed to. In switchback DNA, the 2 strands have sections, known as half-turns, that resemble regular DNA, however the way in which they’re organized makes switchback DNA distinctive.

Usually, DNA is a double helix with right-handed helical sense all through the molecule. In switchback DNA, right-handed half-turns are organized in such a manner that the molecule as a complete is a left-handed double helix. It’s because in the event you hint the spine of DNA alongside the helix, you will see that that after each half-turn, the strands fold again. These variations are illustrated within the diagram under.

We’ve got discovered that switchback DNA’s distinctive construction can have an effect on properties necessary to its potential function in biomedical purposes—issues like structural stability, vulnerability to enzymes, and immunogenic properties, which, for instance, can impression the flexibility of a nanostructure to successfully ship a drug to a specific tissue. Understanding these properties, and determining which may be managed and learn how to management them, is important.

What does the sphere stand to realize by higher understanding switchback DNA?

The outcomes of this examine will assist researchers who make DNA nanostructures enhance their designs utilizing switchback DNA constructing blocks.

For instance, we now know {that a} frequent enzyme known as “DNase I” doesn’t degrade switchback DNA as shortly because it degrades typical B-DNA (the DNA that’s typically present in dwelling organisms). If we wish to use DNA nanostructures to hold medicine to tissues within the physique, we do not need an enzyme to interrupt down the nanostructure earlier than it will possibly attain the goal tissue.

If this occurred, the drug wouldn’t be efficient. We are able to now think about incorporating switchback DNA to assist mitigate this problem, which is a standard roadblock within the subject.

We additionally discovered that there are genetic sequences within the human genome that may doubtlessly fold into switchback DNA. Our outcomes recommend that below some circumstances, DNA with particular repeating patterns might type switchback DNA. These sequences are prevalent within the chromosomes of animals and vegetation, and may undertake structural types about which we all know little or no.

It’s thrilling to know that these sequences can fold into switchback DNA in a check tube below sure circumstances. Whether or not this could occur in a dwelling cell stays to be seen.

As a result of these repetitive sequences are concerned in illnesses equivalent to myotonic dystrophy and Huntington’s illness, this avenue of examine might assist us higher perceive this class of illnesses, and it could additionally assist us uncover new drug targets for these illnesses sooner or later.

What are the most important takeaways from this work?

Our work with switchback DNA reveals that we will “tune” the properties of DNA by folding it into totally different patterns with out chemical modifications. Understanding the properties of switchback DNA will probably be helpful in creating DNA units for biosensing, drug supply, DNA computation and different purposes.

Our findings additionally show that the principles of complementarity that Watson and Crick outlined of their iconic double-helical mannequin of DNA construction must be expanded. Within the mannequin proposed by Watson and Crick, the instructions of the 2 strands are reverse. Which means one finish of the primary strand interacts with the other finish of the second strand.

In switchback DNA, the bottom pairing sample is totally different. Whereas many of the guidelines of complementarity outlined by Watson and Crick apply to switchback DNA, the place of the bottom pairs differs.

Lastly, our speculation that repeat sequences might type switchback DNA constructions opens up fascinating discussions—and future research—on the organic incidence of such non-traditional DNA constructions.