The dynamic biology of bone involving an enormous magnitude of cellular interactions and signaling transduction provides ample biomolecular targets, which can be enhanced or repressed to mediate a rapid regeneration of the impaired bone tissue. The delivery of nucleic acids such as DNA and RNA can enhance the expression of osteogenic proteins. Members of the RNA interference pathway such as miRNA and siRNA can repress negative osteoblast differentiation regulators. Advances in nanomaterials have provided researchers with a plethora of delivery modules that can ensure proper transfection. Combining the nucleic acid carrying vectors with bone scaffolds has met with tremendous success in accomplishing bone formation. Recent years have witnessed the advent of CRISPR and DNA nanostructures in regenerative medicine. This review focuses on the delivery of nucleic acids and touches upon the prospect of CRISPR and DNA nanostructures for bone tissue engineering, emphasizing their potential in treating bone defects.

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