DNA evolved to store genetic information, but in principle this special, chain-like molecule can also be adapted to make new materials. Chemists at The Scripps Research Institute (TSRI) have now published an important demonstration of this repurposing of DNA to create new substances with possible medical applications.
TSRI's Floyd Romesberg and Tingjian Chen, in a study published online in the chemistry journal Angewandte Chemie, showed that they could make several potentially valuable chemical modifications to DNA nucleotides and produce useful quantities of the modified DNA. The chemists demonstrated their new approach by making a DNA-based, water-absorbing hydrogel that ultimately may have multiple medical and scientific uses.
"DNA has some unique properties as a material, and with this new ability to modify it and replicate it like normal DNA, we can really begin to explore some interesting potential applications," said Romesberg, a professor of chemistry at TSRI.
Romesberg's laboratory over the past decade has helped pioneer methods for making modified DNA, with the ultimate goal of developing valuable new medicines, probes and materials -- even artificial life forms. The team reached an important milestone last year with a feat reported in Nature Chemistry: the development of an artificial DNA polymerase enzyme that can make copies of modified DNA, much as normal DNA polymerases replicate normal DNA.
The DNA modifications tested in that study involved only the attachment of fluorine (F) or methoxy (O-CH3) moieties to the sugar backbone of DNA nucleotides -- modifications that in principle would improve the properties of DNA-based drugs. In the new study, Chen and Romesberg demonstrated several other modifications that their polymerase SFM4-3 can replicate and, in so doing, opened the door to the design of modified DNA for a much broader range of applications.
One of the new modifications adds an azido group (N3), a convenient attachment point for many other molecules via a relatively easy set of techniques called "click chemistry," also pioneered at TSRI. The TSRI chemists showed that the SFM4-3 polymerase can replicate azido-modified nucleotides with adequate fidelity and can exponentially amplify strands of this modified DNA using a common laboratory method, polymerase chain reaction (PCR). Click chemistry can then be used to add any of a wide variety of different molecules to the DNA via the azido group.
"With the azido-DNA and click chemistry, we were able to produce highly functionalized DNA, including DNA modified with an intense concentration of fluorescent beacon molecules and DNA marked with a chemical handle called biotin," said Chen, who is a postdoctoral research associate in the Romesberg Laboratory.
The scientists in a more advanced demonstration used click chemistry to fasten multiple DNA strands to a central, azido-modified DNA strand, creating a "bottle brush" structure. They then used the assembly to amplify DNA via PCR to obtain a large mesh of DNA that--to their surprise -- formed a hydrogel when exposed to water.
"Hydrogels are a focus of great interest these days because they have a lot of potential applications, though there are relatively few ways for their controlled production," Romesberg said.
The new DNA-based hydrogel turned out to have some intriguing properties. Chen and Romesberg found that they could dissolve it with DNA-cutting enzymes and later reform it in any desired mold using DNA-joining enzymes, allowing them to form and reform the hydrogel with new stable structures. Test proteins placed within the hydrogel also retained their biochemical activity.
"We think this hydrogel can have applications ranging from novel forms of drug delivery to the growing of cells in three-dimensional cultures," Chen said.
The researchers demonstrated that the SFM4-3 polymerase also can be used to replicate and amplify DNA that has been modified with three other types of additions to the backbone sugar: a chloro (Cl) or amino (NH2) group, or a hydroxyl group (OH) that combines with the backbone to form an arabinose sugar.
Chen and Romesberg are now looking for additional DNA modifications that can be replicated using the SFM4-3 polymerase. At the same time, the researchers are pursuing specific applications of their modified DNA, including novel hydrogels.
"Given that DNA can have different sequences that impart different properties, we can even start to think about evolving nanomaterials with desired activities," Romesberg said.
The study, "Enzymatic synthesis, amplification, and application of DNA with a functionalized backbone," was supported by the U.S. Defense Advanced Research Projects Agency (N66001-14-2-4052).
Madeline McCurry-Schmidt | EurekAlert!
Tracing the evolution of vision
23.08.2019 | University of Göttingen
Caffeine does not influence stingless bees
23.08.2019 | Johannes Gutenberg-Universität Mainz
Since their experimental discovery, magnetic skyrmions - tiny magnetic knots - have moved into the focus of research. Scientists from Hamburg and Kiel have now been able to show that individual magnetic skyrmions with a diameter of only a few nanometres can be stabilised in magnetic metal films even without an external magnetic field. They report on their discovery in the journal Nature Communications.
The existence of magnetic skyrmions as particle-like objects was predicted 30 years ago by theoretical physicists, but could only be proven experimentally in...
Theoretical physicists at Trinity College Dublin are among an international collaboration that has built the world's smallest engine - which, as a single calcium ion, is approximately ten billion times smaller than a car engine.
Work performed by Professor John Goold's QuSys group in Trinity's School of Physics describes the science behind this tiny motor.
Together with the University of Innsbruck, the ETH Zurich and Interactive Fully Electrical Vehicles SRL, Infineon Austria is researching specific questions on the commercial use of quantum computers. With new innovations in design and manufacturing, the partners from universities and industry want to develop affordable components for quantum computers.
Ion traps have proven to be a very successful technology for the control and manipulation of quantum particles. Today, they form the heart of the first...
Experimental progress towards engineering quantized gauge fields coupled to ultracold matter promises a versatile platform to tackle problems ranging from condensed-matter to high-energy physics
The interaction between fields and matter is a recurring theme throughout physics. Classical cases such as the trajectories of one celestial body moving in the...
Soft robots have a distinct advantage over their rigid forebears: they can adapt to complex environments, handle fragile objects and interact safely with humans. Made from silicone, rubber or other stretchable polymers, they are ideal for use in rehabilitation exoskeletons and robotic clothing. Soft bio-inspired robots could one day be deployed to explore remote or dangerous environments.
Most soft robots are actuated by rigid, noisy pumps that push fluids into the machines' moving parts. Because they are connected to these bulky pumps by tubes,...
16.08.2019 | Event News
14.08.2019 | Event News
12.08.2019 | Event News
23.08.2019 | Medical Engineering
23.08.2019 | Power and Electrical Engineering
23.08.2019 | Life Sciences