BioTechniques News
Beatrice Bowlby
A new DNA synthesis method that relies on temperature rather than the endless replacement of reagents and molecular building blocks could prove a vital innovation in the field of biocomputing.
A collaborative South Korean research effort led by Yeongjae Choi of the Korea Advanced Institute of Science and Technology (Daejeon, South Korea) has developed a cheap, efficient method of DNA synthesis that could be used for innovative DNA coding and nanotechnology solutions.
Typical DNA synthesis methods involve a constant cycling of reagents as bases or DNA fragments are swapped in and out during synthesis, making workflows long, expensive and complex. This limits the programmability of these methods, presenting a particular challenge in nanotechnology and biocomputing fields where DNA can be used to code specific information.
To design a method that was more amenable to these applications, and that could overcome the expense and complexity of other synthesis approaches, Choi’s team developed a series of temperature-responsive hairpin DNA molecules that can be added to a reaction mixture with the required reagents for synthesis. Each DNA hairpin essentially acts as a template on which the novel strand can be synthesized. However, each hairpin is designed to remain conformationally closed unless exposed to an ideal temperature range, which is dictated by the length of its primer hybridization site and product dissociation site.
This enables a synthesis approach that can be ‘programmed’ by adding a specific selection of DNA hairpins into the reaction mixture along with a primer. When a specific temperature is reached, the primer can bind the desired hairpin’s now-exposed hybridization site, triggering strand-displacing DNA polymerase to unzip the rest of the hairpin as it synthesizes its complementary sequence as the new product, before then dissociating from the hairpin. This newly formed product can then go on to act as another primer for another hairpin when the temperature is altered.
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Now, I must confess that at this stage I asked myself, “So? What is the point?” If you need to have your desired sequence already synthesized and fragmented into these hairpins, then this seems like a more complicated PCR step after previous arbitrary synthesis of your desired DNA from scratch.
To answer this question, Choi’s team demonstrate several use cases including a DNA data storage writer that can synthesize binary data encoded DNA, a colorimetric temperature indicator and a temperature data logger. The data logger works by including a specific group of hairpins in a reaction mixture, which then essentially provides a ticker tape of temperature changes, their length and order, that the reaction mixture has experienced as different hairpins are incorporated into the synthesized DNA.
Combined with the colorimetric temperature indicator, this enabled them to create a device that would require no external power, and that the researchers say could be used to warn of failures in cold chain logistics and track the temperature fluctuations that products have been exposed to during these exposures.
While much work needs to be done to validate this technology’s efficacy outside of lab conditions, the method underlying it could prove transformational in DNA manufacturing and biocomputing.
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