Protein–nucleic acid hybrid nanostructures for molecular diagnostic applications

Molecular diagnostic technologies empower new clinical opportunities in precision medicine. However, existing approaches face limitations with respect to performance, operation and cost. Biological molecules including proteins and nucleic acids are being increasingly adopted as tools in the development of new molecular diagnostic technologies. In particular, leveraging their complementary properties—the functional diversity of proteins and the precision programmability of nucleic acids—a wide range of protein–nucleic acid hybrid nanostructures have been developed. These hybrid structures take diverse forms, ranging from one-dimensional to three-dimensional hybrids, as static assemblies to dynamic machines, and possess myriad functions to recognize target biomarkers, encode vast information and execute catalytic activities. Motivated by recent advances in this area of molecular nanotechnology, we review the state-of-art design and application of various types of protein–nucleic acid hybrid nanostructures for molecular diagnostics, and present an outlook on the challenges and opportunities for emerging pre-clinical and clinical applications, highlighting the promise for earlier detection, more refined diagnosis and highly tailored treatment decision that ultimately lead to improved patient outcomes.