Researchers from NC State, Duke and the University of Copenhagen have discovered a way to synthesize larger pieces of DNA origami than previously done in a lab setting.
DNA origami is the science of folding DNA into shapes at a nanoscale size.
Thomas LaBean, an associate professor in material sciences engineering and principal investigator of the research, said DNA origami is created by folding a single strand of DNA using a set of shorter synthetic strands.
“What we do is take a long single strand of DNA that is prepared from a biological source and fold up the strand of DNA using a set of short synthetic strands,” LaBean said.
LaBean said, in order to increase the size of the origami, the researchers incorporated separate components of two different viruses.
“We took parts of two different viruses,” LaBean said. “The large virus is called lambda phage, which is 49 kilobases and double-stranded. The smaller one is called M13, which is seven kilobases, but it only packs single strand genome.”
By incorporating the different components of each virus, the researchers created a hybrid virus that was able to produce larger strands that could be used to create DNA origami, LaBean said.
“We had to make the hybrid virus because we wanted to use the bulk of the lambda phage, and we wanted the virus to be packaged as single strand,” LaBean said.
LaBean said the hybrid virus required approximately 1600 synthetic strands to fold it into a piece of DNA origami, which required a large amount of resources.
“Having to purchase 1600 staples would cost around $7000, so one of our colleagues converted ink jet printer heads, and he converted it to a DNA synthesizer that could be used to create the staples that fold the scaffold strand,” LaBean said.
According to LaBean, one of the advantages of using DNA origami is receiving a high percentage of assembly yield that have a high level of uniformity.
“The cool thing about origami is that you get a really nice assembly yield, and we were able to increase the size of the origami by nearly sevenfold while maintaining the efficiency,” LaBean said.
Alexandria Marchi, a postdoctoral student from Duke and the first author of the paper, said the application of DNA origami can be used in several areas of study.
“Eventual applications of the DNA origami technique is in any kind of area where things have to be organized at the single nanometer digit scale, such as biology where things happen at the molecular scale,” Marchi said.
LaBean said one of the major goals of the research is to organize nanoscale materials which can be used to create non-biological devices as well as organize proteins and peptides in molecular assemblies.
“What we’re trying to do with the DNA origami is organize nanoscale materials. One example is where we have small pieces of DNA that bind to an enzyme called thrombin and thereby inhibit blood coagulation. We were able to increase the activity of this inhibitor by nine fold,” LaBean said.
Marchi said another important component of the study was the ability to determine the orientation of the origami by controlling the curvature of the origami.
“We already have this structure where we have functionality on a specific face, and so we have to make sure that face is what is facing upward and that is where the curvature of the DNA origami comes into play,” Marchi said.
Marchi said there were three important points that were highlighted by the publication: controlling the curvature of the origami, increasing the size of the DNA origami and the cost effectiveness of our method by using an ink jet printer head to synthesize staple strands.
The paper titled “Toward Larger DNA Origami” will be published in the journal Nano Letters this month.
