Acute kidney injury (AKI) is a kidney disease with high morbidity and mortality. For example, acute lethality poses a great clinical problem, while chronic inflammation leading to renal fibrosis and late transformation to chronic kidney disease seriously affects the quality of survival of patients. In the very recent pandemic of COVID-19, it is noted that 43% of COVID-19 patients suffer from AKI. As one of the most common concomitant complications, the epidemic of post-COVID kidney disease (COV-AKI) and its long-term effects are most likely to be predicted for global health.

Recently, A. Prof. Zhilei GE from Prof. Chunhai FAN’s group at Shanghai Jiao Tong University and Prof. Mou SHAN’s group at Renji Hospital developed a renal-accumulating DNA nanodevice with exclusive kidney retention for longitudinal protection of AKI and published an article titled Sequential Therapy of Acute Kidney Injury with a DNA Nanodevice on Nano Letters in May 2021 (doi: 10.1021/acs.nanolett.1c01044). Qian CHEN and Fei Ding are co-first authors with Zhilei GE and Shan MOU as co-corresponding authors.

Oxidative stress often occurs in the early stage of AKI. Excessive ROS generated from mitochondrial dysfunction conducts direct damage to cellular proteins and lipids by inducing oxidative stress and inflammation. Subsequently, the activation of the complement component 5a (C5a) system magnifies the inflammatory response, or cytokine storm, which leads to tubular damage and renal dysfunction. To overcome the oxidative stress and inflammatory damage, diverse therapies have been developed to function as antioxidant agents and C5a blockers for renal management.  However, most pharmacotherapies rely on single-factor oriented treatment only function in one stage of the disease and are displaying limited efficacy and lacking of continuous and durable intervention in multi-stage.

To address these issues, this work conjugated 16 anti-C5a aptamers with a rectangular DNA origami nanostructure (rDON) to construct DNA nanodevice. rDONs exhibited a high renal uptake and selective kidney accumulation after intravenous injection. The DNA component served as the ROS scavenger for oxidative species consumption in stage I when massive ROS was generated, while the aC5a aptamer bound with C5a suppressed the intense inflammatory response during stage II. Together, aC5a-rDONs enabled dual-drug combination therapy for sequential protection of AKI in multiple stages. They envision that this method could provide insight to the treatment of COV-AKI both for alleviating renal function and improving outcomes from COVID-19 and open up new applications for DNA nanomachines for disease diagnosis and treatment.