DNA origami and fluorescent probes can precisely release molecular cargo

Developing dynamic systems that respond to molecular signals is becoming increasingly important in nanotechnology, and DNA origami, a technique for programming DNA to create functional nanostructures, is playing a key role in these efforts.

A team led by LMU chemist Philip Tinnefeld has published two studies showing how DNA origami and fluorescent probes can be used to deliver targeted release of molecular cargo.

The researchers report in Angewandte Chemie International Edition the development of a new DNA origami-based sensor that can detect lipid vesicles and precisely deliver their molecular cargo. The sensor works using single-molecule fluorescence resonance energy transfer (smFRET), which measures the distance between two fluorescent molecules.

The system consists of a DNA origami structure with a single strand of DNA protruding from it, labeled with a fluorescent dye at its tip. When the DNA comes into contact with a vesicle, it changes its structure. This changes the distance between the fluorescent label and a second fluorescent molecule on the origami structure, and therefore the fluorescent signal. In this way, the vesicles can be detected.

The sensor is transferred accurately

In a second step, the system can be used as a means to transport molecules, with the sensing strand acting as the molecular cargo that can be delivered into the vesicle. By further improving the system, the researchers were also able to precisely control the transport of the cargo.

Lipid vesicles play important roles in many cellular processes, including molecular transport and signal transduction, and therefore the ability to detect and manipulate them is of particular interest for biotechnological applications such as the development of targeted therapies.

The approach presented here could potentially show how lipid nanoparticles can be loaded with a precisely defined number of molecules for applications such as vaccines. “Our system also offers a promising approach for biological research in terms of improving the understanding and control of cellular processes at the molecular level,” says Tinnefeld.

Controllable structural changes

In a second study recently published in Nature Communications , a second team led by Tinnefeld and Yonggang Ke (Emory University, Atlanta, Georgia) presents a DNA origami structure that undergoes a stepwise allosteric conformational change upon binding of a specific DNA strand.

Using FRET probes, the researchers showed how to follow this process at the molecular level and control the reaction steps in time. Furthermore, they demonstrated how to release the DNA cargo in a targeted manner during this process, opening up new possibilities for controlled reaction cascades.