Engineers use “DNA origami” to identify vaccine design rules

By folding DNA into a virus-like structure, MIT researchers including Professor Darrell Irvine have designed HIV-like particles that provoke a strong response from human immune cells grown in a lab dish. The DNA particles, which closely mimic the size and shape of viruses, are coated with HIV proteins, or antigens, arranged in precise patterns designed to provoke a strong immune response. The researchers are now working on adapting this approach to develop a potential vaccine for SARS-CoV-2, and they anticipate it could work for a wide variety of viral diseases.

Because DNA molecules are highly programmable, scientists have been working since the 1980s on methods to design DNA molecules that could be used for drug delivery and many other applications, most recently using a technique called DNA origami that was invented in 2006 by Paul Rothemund of Caltech.

In 2016, Bathe’s lab developed an algorithm that can automatically design and build arbitrary three-dimensional virus-like shapes using DNA origami. This method offers precise control over the structure of synthetic DNA, allowing researchers to attach a variety of molecules, such as viral antigens, at specific locations.

Natural viruses are nanoparticles with antigens arrayed on the particle surface, and it is thought that the immune system (especially B cells) has evolved to efficiently recognize such particulate antigens. Vaccines are now being developed to mimic natural viral structures, and such nanoparticle vaccines are believed to be very effective at producing a B cell immune response because they are the right size to be carried to the lymphatic vessels, which send them directly to B cells waiting in the lymph nodes. The particles are also the right size to interact with B cells and can present a dense array of viral particles.

The findings from this study have the potential to guide HIV vaccine development, as the HIV antigen used in these studies is currently being tested in a clinical trial in humans, using a protein nanoparticle scaffold.