Editors' ChoiceKidney Disease

DNA folding for renal rescue

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Science Translational Medicine  28 Nov 2018:
Vol. 10, Issue 469, eaav9146
DOI: 10.1126/scitranslmed.aav9146

Abstract

DNA origami nanostructures offer an alternative therapeutic for kidney targeting and treatment of acute kidney injury in mice.

Globally, there are more than 13 million new cases of acute kidney injury (AKI) every year and almost 2 million fatal cases. AKI is characterized by accumulation of waste and decreased urinary output, sometimes within hours of the disease onset. Administration of radiographic contrast agents can cause a reduction in renal function, contributing to injury, and the current gold standard for clinical treatment of contrast-induced AKI is N-acetylcysteine (NAC). However, this treatment is limited by poor bioavailability, which has hindered its clinical applicability to other types of AKI. Using DNA nanotechnology, Jiang and colleagues discovered that DNA origami nanostructures (DONs) elicited therapeutic effects comparable to the gold-standard treatment (NAC) in mice.

Jiang et al. prepared and radiolabeled three different morphologies of DONs—rectangular, triangular, and tubular—and used positron emission tomography (PET) imaging to examine biological response in mice. Noninvasive PET imaging after intravenous injection of DONs showed that all three DONs preferentially accumulated in the kidneys of healthy mice. In addition, PET imaging, blood tests, and histology of kidney sections confirmed that the rectangular DONs were therapeutically efficacious in mice with rhabdomyolysis-induced AKI.

These results suggest that DONs are promising candidates for the treatment of clinical AKI and possibly other renal diseases. DONs have also been used to deliver small molecules for imaging and treatment of cancerous tumors, demonstrating other potential applications of this technology. Although these nanostructures have minimal toxicity, low immunogenicity, and excellent biostability, investigation in a large animal model would be required before clinical translation as a kidney therapeutic. Further experimentation is also required to optimize therapy, but the results of this study suggest that DNA nanotechnology could have important therapeutic indications for kidney-related diseases.

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