These new advances with DNA origami and fluorescent probes allow scientists to regulate molecular cargo release with great accuracy, fueling applications such as targeted therapeutics and advancing the study of biology.
View the Directed: Detecting and Manipulating Lipid Vesicles from BioSurfaces on Helix
As the field of nanotechnology is rapidly expanding, there is a new emphasis on developing systems that are responsive to specific molecular signals.
In this respect, the DNA origami technique — in which DNA can be programmed to self-assemble into predefined functional nanostructures — has become a main technology trend. Chemist Philip Tinnefeld and his group at LMU have now made a significant contribution to this direction.
In their Angewandte Chemie International Edition paper, the researchers describe how they produced a unique DNA-origami-based sensor that can spot lipid vesicles and deliver molecular cargo to them with exceptional control. The sensor is based on single-molecule Fluorescence Resonance Energy Transfer (smFRET), which measures the distance between two fluorescent molecules.
This is essentially a DNA origami structure and it contains just one single stranded DNA arm with a non-yellow dye at its end. This is important because when this DNA strand bumps into another part of the structure, (called a lipid vesicle), its shape changes, which in turn causes it to change colors (= fluorescence) due to how far away it is from a second fluorescent molecule connected on the origami. This is used to find the vesicles.
Considered in itself, the system further has this capability, but the researchers from Vienna have also shown how it is possible to transport molecules with their system – for example, if today’s peptides are seen as molecular cargo equipped on the sensing strand and transferred to the vesicle. Moreover, they have found a method to which ensures the cargo is delivered exactly when and where they want it to be, paving way for new possibilities like therapies with targets.
DNA Origami for Directed Sequential Reaction Cascades
In a follow-up study, also published in Nature Communications, Tinnefeld and Emory University collaborator Yonggang Ke went yet another step further with the DNA origami.
By designing a DNA origami structure that moves through an induced conformational change (called allosteric), the researchers have created a system that can be made to perform logic steps upon binding of additional strands of DNA. The process bordered at molecular detail with the help of FRET Probes by the researchers and made crystal clear how those reaction steps were temporally controlled.
What is more, they have described the release of a DNA load at this specific site and have thus presented new possibilities for reaction cascades. In biological research this can be an important step ahead, as it allows for more efficient insight and control on molecular aspects of cellular activity.
Lipid vesicles are integral to several processes within the cell, including molecular transportation and signal transduction. The interest to identify and control those vesicles has special relevance in biotechnological scenarios, such as designing application-specific vehicles for therapy.
According to the researchers, this method can serve as a means of prospectively filling lipid nanoparticles with an exact number of molecules — something that could be great for uses like vaccines. This powerful tool also opens doors to obtain mechanistic insight into fundamental cellular behaviour.
Conclusion
Research teams under the leadership of Philip Tinnefeld have fundamentally changed this – with their pioneering work molecular manipulations can be done on an entirely new level. They tapped DNA origami and fluorescent probes to create new ways of sensing, shuttling and target-releasing molecules.
The implications of these advancements range from targeted therapeutics to better vaccine delivery systems to a more detailed understanding of the intricate cellular processes that give life to living things. With nanotechnology undergoing a continual growth, the avenues they have opened and the perspectives provided by these investigations are changing the landscape of numerous scientific and medical frontiers.
