Synthetic approaches for copolymers containing nucleic acids and analogues: challenges and opportunities

Deep integration of nucleic acids with other classes of materials has become the basis of many useful technologies. Among these biohybrids, nucleic acid-containing copolymers have seen rapid development in both chemistry and applications. This review focuses on the various synthetic approaches for accessing nucleic acid–polymer biohybrids spanning post-polymerization conjugation, nucleic acids in polymerization, solid-phase synthesis, and nucleoside/nucleobase-functionalized polymers. We highlight the challenges associated with working with nucleic acids with each approach and the ingenuity of the solutions, with the hope of lowering the entry barrier and inspiring further investigations in this exciting area.