March 1, 2024

Building a DNA nanoparticle to be a carrier and medicine

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Illustration of the genetic construct used in this study and the process of generating scaffold and DNA nanoparticles via aPCR and DNA origami, respectively, along with schematic diagram of different DNA nanoparticles used in the study. Primary variations include the number/position of crossovers in the origami architecture and relative accessibility of the T7 RNA polymerase promoter region; the T7 promoter being located in a linear duplex extending from the body of the nanoparticle, incorporated into the nanoparticle, or completely absent. Credit: Scientific Reports (2023). DOI: 10.1038/s41598-023-39777-0

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Illustration of the genetic construct used in this study and the process of generating scaffold and DNA nanoparticles via aPCR and DNA origami, respectively, along with schematic diagram of different DNA nanoparticles used in the study. Primary variations include the number/position of crossovers in the origami architecture and relative accessibility of the T7 RNA polymerase promoter region; the T7 promoter being located in a linear duplex extending from the body of the nanoparticle, incorporated into the nanoparticle, or completely absent. Credit: Scientific Reports (2023). DOI: 10.1038/s41598-023-39777-0

Scientists have been making nanoparticles from strands of DNA for two decades, manipulating the bonds that maintain DNA’s double helix shape to sculpt self-assembling structures that could someday have jaw-dropping medical applications.

The study of DNA nanoparticles, however, has focused mainly on their architecture, transforming the genetic code of life into components for making tiny robots. Two Iowa State University researchers in the department of genetics, development and cell biology – professor Eric Henderson and recent graduate Chang-Yong Oh – hope to change that by showing that nanoscale materials made from DNA can transmit their built-in genetic instructions.

“Until now, most people have explored DNA nanoparticles from an engineering point of view. Little attention has been paid to the information contained in these DNA strands,” Oh said.

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

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

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

Successful frameworks

Henderson came to Iowa State in 1987, but for 14 years he divided his time building 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 that could detect pathogens.

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

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

This took a few years. The next step was to determine whether RNA polymerase, an enzyme for producing RNA molecules from DNA codes, could navigate the extensive folds of DNA origami, Henderson said. A particular concern was whether the polymerase would be blocked by crossovers, the junctions where long strands of DNA are joined by small pieces of DNA called hairpins.

“It turns out not, which is counterintuitive,” Henderson said.

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

“We could create an efficient, targeted delivery system with potential in many fields, including cancer therapy,” he said.

Affordable and durable

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 editing just the genes you want to edit. So that’s the dream, to refine these nanoparticles to target certain cells and tissues,” he said.

However, DNA nanoparticles have other important advantages. They are easy to make, cheap and durable. Getting nanoparticles to self-assemble is as simple as heating a mixture and letting it cool, without the need for special equipment, Oh said.

Thanks in part to the ubiquity of DNA research, yarn and staples are cheap to produce. Despite using them daily, Henderson and Oh are still working on a package of staples purchased from a Coralville manufacturer 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 most challenging conditions, Henderson said. It is a technology that can spread easily.

“DNA is very stable. It was recovered from samples that are more than 1 million years old,” he said.

More information:
Chang Yong Oh et al, In vitro transcription of self-assembled DNA nanoparticles, Scientific Reports (2023). DOI: 10.1038/s41598-023-39777-0

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