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 buildings in numerous shapes that can be utilized for purposes together with drug supply, medical diagnostics and even knowledge storage.
RNA Institute researchers together with Postdoctoral Fellow Bharath Raj Madhanagopal and Senior Analysis Scientist Arun Richard Chandrasekaran, along with a workforce 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 varieties of nanostructures with biomedical purposes.
Their findings have been revealed right now 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 important-
Many know DNA because the molecule that shops the genetic data that’s handed from one technology to the following. The chemical properties of DNA that make it a wonderful molecule for storing genetic data additionally make it a helpful building materials -; particularly in terms of making tiny objects, as small as a number of nanometers.
The sequences of the 4 nucleobases in DNA -; adenine, guanine, thymine and cytosine -; are inherently programmable. It is because adenine all the time pairs with thymine, and guanine with cytosine. These dependable patterns in base pairing enable 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 glorious precision within the dimension of the buildings. We will additionally make objects of numerous shapes and architectural intricacies -; capabilities that aren’t simply achieved utilizing different applied sciences. DNA nanostructures are actually being developed to be used in drug supply, diagnostics, and knowledge storage, to call a number of purposes.
What’s ‘switchback DNA’-
Simply as we use bricks to assemble buildings, we use nanometer-sized constructing blocks known as “motifs” and “tiles” fabricated from DNA to create elaborate buildings in DNA nanotechnology. Much like how bricks can come in numerous sizes and shapes, so can motifs and tiles. Creating these structural motifs and understanding their properties is the inspiration of DNA nanotechnology analysis.
“Switchback DNA” is without doubt one of the earliest DNA motifs designed by Nadrian Seeman, the founding father of the sector of DNA nanotechnology. We needed to discover how its curious structural options would manifest in nanostructures. By finding out the properties of switchback DNA, we imagine we will create much more numerous DNA-based nano-objects with unique properties.
What makes switchback DNA unique-
Switchback DNA has solely two strands, so it may be immediately in contrast with the double helical construction of DNA that everybody is conversant in. 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 method that the molecule as a complete is a left-handed double helix. It is because in case you hint the spine of DNA alongside the helix, you can see that after each half-turn, the strands fold again. These variations are illustrated within the diagram above.
We’ve got discovered that switchback DNA’s distinctive construction can have an effect on properties necessary to its potential position in biomedical purposes -; issues like structural stability, vulnerability to enzymes, and immunogenic properties, which, for instance, can affect the power of a nanostructure to successfully ship a drug to a selected tissue. Understanding these properties, and determining which might be managed and easy methods to management them, is essential.
What does the sector 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} widespread enzyme known as “DNase I” doesn’t degrade switchback DNA as rapidly because it degrades typical B-DNA (the DNA that’s usually present in dwelling organisms). If we wish to use DNA nanostructures to hold medication to tissues within the physique, we do not need an enzyme to interrupt down the nanostructure earlier than it might probably attain the goal tissue. If this occurred, the drug wouldn’t be efficient. We will now take into account incorporating switchback DNA to assist mitigate this problem, which is a typical 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 beneath some circumstances, DNA with particular repeating patterns may type switchback DNA. These sequences are prevalent within the chromosomes of animals and vegetation, and may undertake structural varieties 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 beneath 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 reminiscent of myotonic dystrophy and Huntington’s illness, this avenue of examine might assist us higher perceive this class of illnesses, and it might additionally assist us uncover new drug targets for these illnesses sooner or later.
What are the largest takeaways from this work-
Our work with switchback DNA exhibits that we will “tune” the properties of DNA by folding it into totally different patterns with out chemical modifications. Understanding properties of switchback DNA shall be helpful in creating DNA units for biosensing, drug supply, DNA computation and different purposes.
Our findings additionally show that the foundations 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 course of the 2 strands are reverse. Meaning 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 may type switchback DNA buildings opens up fascinating discussions-;and future studies-;on the organic incidence of such non-traditional DNA buildings.