Researchers from LMU have unveiled two significant studies that pave the way for innovative biotechnological applications.
Dynamic systems that respond to molecular signals are becoming essential in the realm of nanotechnology. A pivotal aspect of this is the DNA origami technique, which allows for the programming of DNA to create functional nanostructures. Teams headed by LMU chemist Philip Tinnefeld have published two studies demonstrating how DNA origami and fluorescent probes can facilitate the targeted release of molecular cargo.
In the journal Angewandte Chemie, the researchers describe their creation of a novel DNA origami-based sensor designed to detect lipid vesicles and deliver molecular payloads to them with high accuracy. This sensor operates on the principle of single-molecule Fluorescence Resonance Energy Transfer (smFRET), which measures the distance between two fluorescent molecules. The system features a DNA origami framework that has a single-stranded DNA protruding from it, with a fluorescent dye attached at its tip. When this DNA encounters vesicles, its shape changes, leading to a shift in the fluorescent signal as the distance varies between the fluorescent label and another fluorescent molecule on the origami. This mechanism enables the detection of vesicles.
Precision in Sensor Delivery
Following detection, the system can also act as a transport mechanism for molecules, with the sensing strand functioning as molecular cargo that can be delivered to the vesicle. Through further modifications, the researchers were able to refine the process of cargo transfer with precision.
Lipid vesicles are crucial in various cellular functions, including molecular transport and signaling. Hence, the ability to identify and manipulate them is particularly valuable for biotechnological advancements, especially in developing targeted therapies. The methodology presented could enable precise loading of lipid nanoparticles with a defined number of molecules, which is relevant for applications like vaccines. “Our system also provides exciting possibilities for biological research aimed at gaining a deeper understanding and control over cellular processes at the molecular level,” states Tinnefeld.
Managed Structural Changes
The second study, published in Nature Communications, features another team led by Tinnefeld and Yonggang Ke from Emory University. They present a DNA origami structure that undergoes a sequential allosteric conformational change when specific DNA strands bind to it. By utilizing FRET probes, the researchers tracked this reaction at a molecular level, demonstrating that the timing of these reaction steps can be controlled. They also revealed how a DNA cargo could be released in a targeted fashion during this process, which opens new avenues for orchestrating controlled reaction sequences.
