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Research Field Drug discovery

DONs' Potential Unfolds

Designed and “folded” into shape using base-pair interactions, DNA origami nanostructures (DONs) have already been applied in oncology – both in imaging and for the delivery of cytotoxic drugs. Now, researchers are evaluating the potential of these three-dimensional molecular scaffolds in the treatment of acute kidney injury (AKI) (1) – a common condition with serious implications that range from minor loss of function to complete kidney failure. Despite its link to increased mortality (in both the short and long term), no specific pharmacologic treatment exists.

According to the researchers, DONs have numerous advantages as potential therapeutic agents, including minimal toxicity, low immunogenicity, and excellent bio stability. But what about biodistribution? To find out more, the multinational team injected three different radiolabeled nanostructures – rectangular, triangular and tubular – into the tails of mice. Using positron emission tomography (PET), the researchers discovered that all three intact DONs were preferentially accumulated in the mice kidneys at 3 and 12 hours post-injection – but started to clear after 24 hours.

Spurred on by the results, the team decided to test the efficacy of the DONs in mice with rhabdomyolysis-induced AKI. The outcomes showed promise – at least, for the rectangular DONs (the triangular and tubular DONs showed no significant effect). Using PET, blood tests and kidney tissue staining, the researchers found that there was significantly less tissue damage present in the treated mice. The team theorize that the rectangular DON may have acted as a scavenger for reactive oxygen species (ROS), which account for a significant proportion of the damage associated with AKI.

“Further studies are needed to determine optimum strategies for improving the kidney-targeting efficiencies of DNA origami frameworks,” the authors explained, whilst hinting that further optimization of the nanostructures could boost delivery efficacy.

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  1. D Jiang et al., “DNA origami nanostructures can exhibit preferential renal uptake and alleviate acute kidney injury.” Nat Biomed Eng, 2, 865-877 (2018). PMID: 30505626
About the Author
Jonathan James

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