Infection capsid proteins, the protective shield for a viruss genome, can serve as a base for developing meticulously structured protein assemblies. The scientific team resolved this difficulty by creating a “structured genome” design template for the assembly of capsid proteins.” We have actually found a simple but effective strategy to (re) direct capsid proteins to a desired shape. Our approach is versatile and for that reason not restricted to a single capsid protein type, as we demonstrated with capsid proteins from four various infections. In addition, we can fine-tune our template to be more application-relevant, for instance by incorporating RNA into the origami, which might subsequently be translated into site-specific or beneficial proteins,” discusses Aalto professor Mauri Kostiainen, leader of the research job.
DNA origami nanostructures (blue) can be utilized to configure the shape of infection particles (grey). The native capsid with a size of 28 nanometers is displayed in green-grey. Credit: Mauri A. Kostiainen/Aalto University
Proteins that encapsulate infections can be formed into defined shapes using DNA and RNA origami nanostructures.
Bioengineers have found an approach to customize the shapes and size of virus particles. This new technique, which involves combining viral protein foundation and DNA design templates, provides possible applications in the fields of vaccine creation and drug shipment.
Using Virus Capsid Proteins
Infection capsid proteins, the protective shield for an infections genome, can serve as a base for creating meticulously structured protein assemblies. Their shapes and geometry mainly depend on the virus strain. Reprogramming these assemblies, irrespective of the initial viral plan, provides an alluring possibility in locations such as drug shipment and vaccine advancement.
The clinical team resolved this challenge by producing a “structured genome” design template for the assembly of capsid proteins. They made use of rigid DNA origami structures to avoid deformation of the versatile genome and the formation of undesirable shapes. These structures are small in size, varying from tens to hundreds of nanometers, but entirely made of DNA, which is specifically folded into the preferred template shape.
The Role of Electrostatic Interactions
” Our method is based upon electrostatic interactions in between the negative charge of the DNA nanostructures and a positively charged domain of the capsid proteins, coupled with intrinsic interactions in between the single proteins. By altering the amount of protein utilized, we can tweak the variety of highly-ordered protein layers, which encapsulate the DNA origami,” says Iris Seitz, lead author and doctoral scientist at Aalto University.
” By utilizing DNA origami as a design template, we can direct the capsid proteins into a user-defined shapes and size, resulting in assemblies which are distinct, both in length and diameter. By testing a variety of DNA origami structures, we also discovered how the templates geometry affected the entire assembly,” Seitz adds.
Cryogenic Electron Microscopy Imaging
” With the help of cryogenic electron microscopy imaging, we were able to picture the highly bought proteins upon assembly and, with that, measure even small modifications in the geometry of the assembly developing from various design templates,” discusses professor Juha Huiskonen, a working together researcher from the University of Helsinki.
Significance and Applications
” We have actually discovered a efficient however easy method to (re) direct capsid proteins to a wanted shape. Our approach is adaptable and for that reason not limited to a single capsid protein type, as we demonstrated with capsid proteins from four various viruses. Additionally, we can tweak our template to be more application-relevant, for instance by incorporating RNA into the origami, which might consequently be equated into site-specific or useful proteins,” explains Aalto teacher Mauri Kostiainen, leader of the research job.
Although DNA origami structures are an appealing product for interfacing biological systems, they struggle with instability, specifically in the presence of DNA-degrading enzymes.
In experiments, nevertheless, “we can clearly observe that the protein layer effectively protects the encapsulated DNA nanostructures from degradation. By combining security with the practical properties of nucleic acid origami, including the possibility to provide DNA or messenger RNA together with other freight molecules, our company believe that our approach offers interesting future instructions for biomedical engineering,” concludes Kostiainen.
Referral: “DNA-origami-directed infection capsid polymorphism” by Iris Seitz, Sharon Saarinen, Esa-Pekka Kumpula, Donna McNeale, Eduardo Anaya-Plaza, Vili Lampinen, Vesa P. Hytönen, Frank Sainsbury, Jeroen J. L. M. Cornelissen, Veikko Linko, Juha T. Huiskonen and Mauri A. Kostiainen, 17 July 2023, Nature Nanotechnology.DOI: 10.1038/ s41565-023-01443-x.
This work was carried out jointly at Aalto University (Finland) with scientists from the University of Helsinki (Finland), Griffith University (Australia), Tampere University (Finland) and University of Twente (The Netherlands).