Patients with acute kidney injury (AKI) frequently require kidney transplantation and supportive therapies, such as rehydration and dialysis. Here, we show that radiolabelled DNA origami nanostructures (DONs) with rectangular, triangular and tubular shapes accumulate preferentially in the kidneys of healthy mice and mice with rhabdomyolysis-induced AKI, and that rectangular DONs have renal-protective properties, with efficacy similar to the antioxidant N-acetylcysteine—a clinically used drug that ameliorates contrast-induced AKI and protects kidney function from nephrotoxic agents. We evaluated the biodistribution of DONs non-invasively via positron emission tomography, and the efficacy of rectangular DONs in the treatment of AKI via dynamic positron emission tomography imaging with 68Ga-EDTA, blood tests and kidney tissue staining. DNA-based nanostructures could become a source of therapeutic agents for the treatment of AKI and other renal diseases.
There remains a great challenge in the sensitive detection of microRNA because of the short length and low abundance of microRNAs in cells. Here, we have demonstrated an ultrasensitive detection platform for microRNA by combining the tetrahedral DNA nanostructure probes and hybridization chain reaction (HCR) amplification. The detection limits for DNA and microRNA are 100 aM and 10 aM (corresponding to 600 microRNAs in a 100 μL sample), respectively. Compared to the widely used supersandwich amplification, the detection limits are improved by 3 orders of magnitude. The uncontrolled surface immobilization and consumption of target molecules that limit the amplification efficiency of supersandwich are eliminated in our platform. Taking advantage of DNA nanotechnology, we employed three-dimensional tetrahedral DNA nanostructure as the scaffold to immobilize DNA recognition probes to increase the reactivity and accessibility, while DNA nanowire tentacles are used for efficient signal amplification by capturing multiple catalytic enzymes in a highly ordered way. The synergetic effect of DNA tetrahedron and nanowire tentacles have proven to greatly improve sensitivity for both DNA and microRNA detection.
The
blooming field of structural DNA nanotechnology harnessing
the material properties of nucleic acids has attracted widespread
interest. The exploitation of the precise and programmable Watson–Crick
base pairing of DNA or RNA has led to the development of exquisite
nucleic acid nanostructures from one to three dimensions. The advances
of computer-aided tools facilitate automated design of DNA nanostructures
with various sizes and shapes. Especially, the construction of shell
or skeleton DNA frameworks, or more recently dubbed “framework
nucleic acids” (FNAs) provides a means to organize molecules
or nanoparticles with nanometer precision. The intrinsic biological
properties and tailorable functionalities of FNAs hold great promise
for physical, chemical, and biological applications. This Perspective
highlights state-of-the-art design and construction, of precisely
assembled FNAs, and outlines the challenges and opportunities for
exploiting the structural potential of FNAs for translational applications.
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