Bioinspired designer DNA NanoGripper for virus sensing and potential inhibition

DNA has shown great biocompatibility, programmable mechanical properties, and precise structural addressability at the nanometer scale, rendering it a material for constructing versatile nanorobots for biomedical applications. Here, we present the design principle, synthesis, and characterization of a DNA nanorobotic hand, called DNA NanoGripper, that contains a palm and four bendable fingers as inspired by naturally evolved human hands, bird claws, and bacteriophages. Each NanoGripper finger consists of three phalanges connected by three rotatable joints that are bendable in response to the binding of other entities. NanoGripper functions are enabled and driven by the interactions between moieties attached to the fingers and their binding partners. We demonstrate that the NanoGripper can be engineered to effectively interact with and capture nanometer-scale objects, including gold nanoparticles, gold NanoUrchins, and SARS-CoV-2 virions. With multiple DNA aptamer nanoswitches programmed to generate a fluorescent signal that is enhanced on a photonic crystal platform, the NanoGripper functions as a highly sensitive biosensor that selectively detects intact SARS-CoV-2 virions in human saliva with a limit of detection of ~100 copies per milliliter, providing a sensitivity equal to that of reverse transcription quantitative polymerase chain reaction (RT-qPCR). Quantified by flow cytometry assays, we demonstrated that the NanoGripper-aptamer complex can effectively block viral entry into the host cells, suggesting its potential for inhibiting virus infections. The design, synthesis, and characterization of a sophisticated nanomachine that can be tailored for specific applications highlight a promising pathway toward feasible and efficient solutions to the detection and potential inhibition of virus infections. A human hand–like designer DNA nanobot for specific applications was designed, synthesized, and characterized. Recent DNA nanostructures have been functionalized to detect or block viruses but have lacked the dexterity to grasp individual virus particles. Here, Zhou et al. designed and synthesized a DNA NanoGripper from a single DNA origami piece that resembles a hand with a palm and four bendable finger-like structures. The NanoGripper’s fingers can be functionalized with ssDNA or aptamers to recognize and bind to different targets such as gold nanoparticles and SARS-CoV-2. Experiments showed that the NanoGripper can successfully detect SARS-CoV-2 virions in a human saliva sample with comparable sensitivity to a PCR test and has the potential to inhibit virus infections. —Melisa Yashinski