Rational Optimization of an Aptamer Specific to the Surface of Lung-Cancer Cells Using Mathematical Modeling and Small-Angle X-ray Scattering

Aptamers, short oligonucleotides, are capable of high-affinity binding to targets due to their unique structure. Shortening the aptamer while maintaining the active site will increase the affinity and reduce the cost of synthesis. Using the example of the aptamer LC-224, a method for rational optimization of its length and verification of the validity of the developed approach is tested. The use of computer modeling and small-angle X‑ray scattering shows the possibility of optimizing the aptamer structure by removing nucleotides that do not participate in binding to the target. It is shown that truncation of the aptamer does not reduce the affinity and specificity of the DNA aptamer. Thus, theoretical and experimental studies demonstrate successful experience in optimizing the structure of a DNA aptamer by shortening it without compromising its affinity and specificity for its target.