Building a DNA nanoparticle that is both a carrier and a drug

Scientists have been making nanoparticles from DNA strands for two decades, manipulating the bonds that maintain DNA’s double-helical shape to sculpt self-assembled structures that could one day have mind-blowing medical applications.

The study of DNA nanoparticles, however, has mainly focused on their architecture, transforming the genetic code of life into components to make tiny robots. Two Iowa State University researchers in the Department of Genetics, Developmental and Cell Biology – Professor Eric Henderson and recent doctoral student Chang-Yong Oh – hope to change that by showing that nanoscale materials made of DNA can transmit their built-in genetic instructions.

“Until now, most people have explored DNA nanoparticles from a technical perspective. Little attention has been paid to the information contained in these DNA strands,” Oh said.

In a recent article published in the journal Scientific reports, Henderson and Oh described how they constructed DNA nanoparticles capable of expressing genetic code. Having the ability to carry genes increases the potential of DNA nanotechnology.

“These structures could be both the vector and the drug,” Henderson said.

Henderson and Oh said they were among the world’s first research teams to create a DNA nanoparticle that expresses its genetic code. The Iowa State University Research Foundation filed a patent application related to the research in 2023.

High-performance structures

Henderson came to Iowa State in 1987, but for 14 years he split his time creating a startup called BioForce Nanosciences. After returning to Iowa State full-time in 2008, he began working on DNA origami, a newly developed method for creating complex self-assembled nanostructures from long single strands of DNA .

Henderson and a former graduate student, Divita Mathur, now an assistant professor at Case Western University, designed a nanomachine biosensor capable of detecting pathogens.

This work left a lingering question: what about the genes that these structures carry? Could DNA origami express the genetic information embedded within itself?

The first step was to figure out how to create DNA origami with single strands that have specific genetic sequences, as opposed to the strands traditionally used to create nanoparticles.

It took a few years. The next step was to determine whether RNA polymerase, an enzyme for making RNA molecules from DNA codes, could navigate the vast folds of DNA origami, Henderson said. Of particular concern was whether the polymerase would be blocked by crossovers, the junctions where long strands of DNA are joined by short pieces of DNA called staples.

“It turns out that’s not the case, which is counterintuitive,” Henderson said.

Although crossovers and complex architecture do not stop the transcription process of producing RNA, the design of a DNA nanostructure affects the efficiency of transcription. Dense structures produce less RNA, implying that nanoparticle design could be fine-tuned to inhibit or promote intended functions, Oh said.

“We could create an efficient, targeted delivery system that would have potential in many areas, including cancer treatment,” he said.

Affordable and sustainable

The potential for precision is part of what makes DNA nanoparticles an exciting possibility, Henderson said.

“Gene editing is incredibly powerful, but one of the hardest parts of gene editing is just editing the genes that you want to change. So that’s the dream: refining these nanoparticles to target certain cells and certain fabrics,” he said.

However, DNA nanoparticles have other major advantages. They are easy to make, inexpensive and durable. Getting nanoparticles to self-assemble is as simple as heating a mixture and letting it cool, with no special equipment needed, Oh said.

Thanks in part to the ubiquity of DNA research, strands and staples are inexpensive to produce. Although they use them daily, Henderson and Oh still work on a package of basic products purchased from a manufacturer in Coralville several years ago for a few hundred dollars.

And the components, which can be stored in powder form, have a long shelf life, even in the harshest conditions, Henderson said. This is a technology that could easily spread.

“The DNA is very stable. It has been recovered from samples over a million years old,” he said.