Design Considerations for Next-Generation Protein–Nucleic Acid Conjugates in Biorecognition and Therapy

Abstract Proteins and nucleic acids represent nature’s most versatile biomolecules. By leveraging the functionality of proteins and the programmability of nucleic acids, along with the exquisite recognition properties of both, protein-nucleic acid conjugates can unlock hybrid systems that outperform either component alone. In this Viewpoint, we discuss emerging applications of protein–nucleic acid conjugates in biorecognition and therapeutics. As detection tools, these structures can identify molecules in complex media and single living cells with high selectivity or amplify signals to create assays with ultralow limits of detection. For therapeutics, they can be engineered to regulate genes in a tissue-selective manner, act as immunotherapies, or form the basis of new biomaterials with unique in vitro and in vivo properties. We end by focusing on the outstanding challenges that remain before the full potential of these structures is realized in revolutionizing diagnostics and medicine.