New efficient way to engineer nanostructures mimicking natural immune response complexes

Today, a step towards this goal has been taken in the publication of a new efficient method for connecting small pieces of proteins attached to short strings of DNA to antibodies. The method is developed by a research team at Novo Nordisk and Kurt Gothelf's research group. The work is also performed in the framework of the Center for Multifunctional Biomolecular Drug Design which started last year under the Novo Nordisk Foundation Challenge Programme.

Mimicking naturally occurring molecules and components, like antibodies, can serve as a powerful tool in studying biological mechanisms. Here DNA nanotechnology is utilized to integrate protein function and DNA structures, where nucleic acids (DNA building blocks) are used as biological engineering materials rather than as the carriers of genetic information in living cells. The advantages of DNA nanostructures are that the production is scalable and can be made in the dimensions relevant for clinical use and for scientific experiments with cells. Connecting proteins to DNA structures adds complex functionalities, which can provide the structures with the ability to act as drugs, extend the lifespan of the molecules or direct the structures towards specific molecules.

Here the researchers show the development of a new method for connecting a piece of DNA to a specific spot on Immunoglobulin Gs (IgGs), which are the most prevalent antibodies in our blood stream. The connection (labeling) is directed by a small piece of protein (peptide), with affinity to a specific spot on the antibody, which positions a single piece of double-string DNA. The peptide along with half of the DNA double-string is easily removed afterwards, and leaves a single string of DNA chemically bound to the antibody. This makes it possible to connect the DNA-antibody conjugate to structures with a complementary DNA string attached.

The DNA-conjugates have been exploited in forming an IgM-like nanostructure, which is a large star-like pentameric DNA nanostructure made by assembling five DNA-antibody conjugates.