Harnessing DNA for immunotherapy: Cancer, infectious diseases, and beyond

Despite the rapid development of immunotherapy, low response rates, poor therapeutic outcomes and severe side effects still limit their implementation, making the augmentation of immunotherapy an important goal for current research. DNA, which has principally been recognized for its functions of encoding genetic information, has recently attracted research interest due to its emerging role in immune modulation. Inspired by the intrinsic DNA-sensing signaling that triggers the host defense in response to foreign DNA, DNA or nucleic acid-based immune stimulators have been used in the prevention and treatment of various diseases. Besides that, DNA vaccines allow the synthesis of target proteins in host cells, subsequently inducing recognition of these antigens to provoke immune responses. On this basis, researchers have designed numerous vehicles for DNA and nucleic acid delivery to regulate immune systems. Additionally, DNA nanostructures have also been implemented as vaccine delivery systems to elicit strong immune responses against pathogens and diseased cells. This review will introduce the mechanism of harnessing DNA-mediated immunity for the prevention and treatment of diseases, summarize recent progress, and envisage their future applications and challenges.