Computational Analysis of Aptamer-Based DNA Origami for Targeting Glioblastoma

Glioblastoma is an aggressive and lethal brain tumor known for its rapid growth and resistance to surgi- cal removal. Its invasive nature and tendency to recur make effective treatment particularly challenging. An aptamer is a short, single-stranded nucleic acid that folds into a specific structure and binds to target molecules, potentially leading to the treatment of diseases. DNA origami is a technique that involves folding DNA into precise nanostructures for medical applications. We hypothesize that these aptamers will bind to the binding sites of the CD19 and CD71 receptors, thereby facilitating the interaction between CAR T-cells and cancer cells. In the current work, we have designed DNA origami-bound aptamers target- ing the CD71 receptors of cancer cells and the CD19 receptors of CAR T cells. First, we modeled the CD19 and CD71 receptors using the AlphaFold 3 software. Next, we modeled the aptamers using the Vfold2D and Vfold3D software. Following this, molecular docking of aptamer on the receptors was performed with the HDOCK server. The docking results show that the aptamer binds to the predicted binding sites of the receptors and could act as a binder to bring CAR T cells closer to cancer cells, potentially result- ing in cancer cell apoptosis. The DNA origami design was created with cadnano software. Finally, the DNA origami was bound with the aptamer and the receptor. This study lays the groundwork for a novel DNA origami-aptamer-based system that could enhance the precision and efficacy of CAR T-cell therapy in glioblastoma treatment.