James Watson and Francis Crick’s identification of the double helix structure of DNA in 1953 gave rise to the field of molecular biology as we know it today. Since their discovery, modern molecular biologists have been expanding upon our knowledge about this once-elusive source of the genetic code. Today, thanks to enormous advancements in technology, molecular biologists can perform DNA research techniques once unheard of in the field.
Introduction of Commercial Nanopore Sequencing
The very first commercial nanopore DNA sequencing device was created by Danish firm Oxford Nanopore Technologies (ONT). In 2015, the team from ONT aimed to improve upon the traditional method of DNA sequencing utilized by the Human Genome Project. Instead of using actual polymerase-based DNA synthesis to study and sequence the DNA, nanopore sequencing monitors ionic changes to predict which DNA bases are present.
Nanopore sequencing utilizes a synthetic, engineered transmembranal protein known as a nanopore. Researchers pass the strands of a DNA chain through the nanopore and monitor the resulting ionic changes. From these changes, researchers can infer the bases that are present within the DNA and sequence it much more efficiently and effectively than traditional methods.
Artificial DNA Folding Techniques
After the commercial success of ONT’s DNA nanopore sequencing, researchers from various laboratories around the world looked to expand upon the idea. Many of these teams looked to construct larger nanopores that would allow proteins to pass through the cell membrane, creating a protein sensor. In order to do this, researchers needed to pursue artificial protein design.
Recently, the same Danish team that developed commercial nanopore technology established a new technique for creating artificial DNA. The technique involves folding DNA into complex structures using an alternative method of protein folding that was developed approximately a decade ago. Protein stability plays a key part in understanding the molecular basis of different diseases. Known as the 3D Origami Technique, this method of folding was created to fold DNA into a large nanopore that would allow large proteins to pass through a cell membrane.
Implications of Large DNA Nanopores
Through the use of a powerful electron microscope, researchers were able to manipulate the DNA nanopore to allow multiple large-sized macromolecules to pass through. Even more importantly, the team developed a gating system to allow the nanopore to sense biomolecules within a liquid solution as well as a controllable plug for the nanopore, allowing control over the size of molecules that the nanopore allows to pass.
Collectively, these efforts allow researchers a label-free method of identifying macromolecules as they pass through a highly controlled nanopore. With these advancements, researchers hope to one day install nanopore sensors directly into cells harboring disease. This could pave the way for targeting, controlling, and identifying macromolecules passing through the cell membrane. These sensors could perform diagnosis at the cell level, allowing more accurate and timely diagnosis of targeted diseases.
More research regarding protein folding, DNA folding, and artificial nanopores is likely to come. This could make for promising developments in several fields and offer advancements into the diagnosis and treatment of several diseases. As researchers continue to develop applications for clinical use, the future of nanopores looks very promising.