DNA and RNA nanostructures, e.g., DNA Origami, have great potential in biological applications, including extracellular matrix scaffolds and delivery vehicles for drugs and gene therapies. While folding DNA origami under physiological conditions is plausible, significant challenges and limitations remain. For example, isothermal annealing of DNA origami is limited to specific structures (mainly 2D shapes) and results in very low yields due to insufficient counterionic screening and kinetic traps, where structures are stuck in intermediates states during folding at room or physiologically relevant temperatures.
Researchers at Arizona State University and collaborators have developed a new method for assembling 2D and 3D DNA and RNA nanostructures under physiological conditions using positively charged or latently positively charged peptides, the latter of which require enzymes or chemical signals to activate their positive charges. Utilizing these peptides instead of multivalent metal ions to stabilize Watson-Crick base-pairing, isothermal self-assembly or folding of DNA nanostructures has been achieved. This approach could potentially extend to peptides with diverse functional moieties, offering new avenues to enhance the functionalities of nucleic acid-based nanoarchitectures.
Potential Applications
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2D and 3D DNA origami nanostructure folding under physiological conditions
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Extracellular matrix scaffolds
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Drug/gene therapy carrier or cell-targeted delivery vehicle
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Biomedicine
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Bionanotechnology e.g. nanorobots or nanomachines
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Benefits and Advantages
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Avoids kinetic trapping so that folding can be both thermal and isothermal
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The peptides allow for coordinate chemistry and proper folding of the nanostructure
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Results in higher yields compared to other isothermal techniques
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Works on both 2D and 3D origami structures
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Easily programmable
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Does not require the use of multivalent metal ions to stabilize base pairs
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Enables convenient functionalization of nucleic acid nanoarchitectures.
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