Engineering Functional DNA–Protein Conjugates for Biosensing, Biomedical, and Nanoassembly Applications

DNA and protein are the most important two classes of biomacromolecules forming the basis of life. The conjugation of the two using crosslinking chemistries enables a combination of molecular recognition, enzymatic catalysis, and Watson–Crick hybridization properties. The DNA–protein conjugate with combined properties enables a broad range of applications, such as sensitive and selective bioassays, therapeutic agents, and building blocks for programmable nanoassemblies. In this review, we survey the conjugates from the aspects of conjugation chemistries as well as applications in biomedical and nanotechnology fields. We highlight the functions of both biological moieties of a conjugate for target binding and signal transduction in bioassays. We also review the use of DNA–protein conjugates for the construction of a variety of functional and dynamic nanostructures, from isolated hybrid cages to three-dimensional (3D) protein crystalline lattices. Moreover, these conjugates have been used as carriers to deliver enzymes or functional nucleic acids for disease treatments and gene editing.