Scientists at the University of Alabama in the UA 3D Printing Lab have created the first 3D print of a G-quadruplex DNA sequence and their model will give researchers a tactile tool in their fight against cancer.
G-quadruplexes – also known as G-tetrads – are nucleic acid sequences rich in guanine capable of forming four-stranded structures. Such G-tetrads can be made of DNA, RNA, LNA, and PNA, and depending on the direction in which their strands are oriented, they might also be described as parallel or antiparallel.
Dr. Vincent F. Scalfani, science and engineering librarian at UA Libraries, along with Dr. Stephan A. Ohnmacht and Dr. Stephen Neidle who serve as professors at the School of Pharmacy at University College London, used data from laboratory X-ray crystallography to create a model representation of the G-quadruplex molecule, and the drug targeting it, which can be output via 3D printing.
"Preparing the G-qaudruplex DNA sequence for 3D printing was a challenge and certainly pushed the limits of what we thought was possible in the UA 3D Lab," Scalfani said. "The structure is extremely intricate, containing multiple areas of stacked functional groups that are all surrounded by a common outer loop. The 3D printed G-quadruplex is stunning. You can see all of the symmetry, facets and angles within the molecule."
According to Scalfani, he imagines that the model will give students and researchers a better visual handle on the molecule's structural makeup. He added that the work is already in use by researchers doing pre-clinical studies on pancreatic cancer cures.
Ohnmacht says it's the ability to hold and closely examine such DNA sequences which gives researchers a better understanding of how best to target various elements of a sequence with treatments. He says previous techniques, usually based on two-dimensional images, were less than satisfactory.
"Having a live model is invaluable. Visualizing distances of bonds, electrostatic interactions and angles is easy and allows for further optimization of these anti-cancer molecules," Ohnmacht said. "The printed 3D model is actually a real molecular structure that has been designed, synthesized and then crystallized in the London labs. G-quadruplex DNA is unusual as it's four-stranded – not two stranded – like 'normal' double helical DNA."
Scientists and researchers at Yale University have also 3D printed complex neural structural models for use as training and visualization aids.