Plasmid DNA and intracellular DNA (pDNA)

Plasmid DNA (pDNA) and intracellular DNA represent double-stranded DNA molecules that function as either therapeutic vectors or potent immunological triggers within the cellular environment. In the context of gene therapy and DNA vaccines, pDNA is engineered to enter the nucleus and utilize host machinery to express specific proteins or antigens, offering a stable and non-viral method for treating genetic diseases or inducing immunity [1]. Conversely, the presence of DNA in the cytoplasm—often resulting from viral infection, cellular damage, or nuclear leakage—is recognized as a Danger-Associated Molecular Pattern (DAMP) by the cGAS-STING pathway [2]. This recognition initiates a robust innate immune response characterized by the secretion of Type I interferons and other cytokines. Dysregulation of intracellular DNA sensing is a key driver in autoimmune pathologies, such as systemic lupus erythematosus (SLE), where the failure to clear self-DNA leads to chronic inflammation [3]. Consequently, these molecules are central to both the development of novel vaccines and the design of inhibitors targeting inflammatory signaling pathways. Citations: [1] Liu, M. A. (2019). A Comparison of Plasmid DNA and mRNA as Vaccine Technologies. Vaccines. [2] Hopfner, K. P., & Hornung, V. (2020). Molecular mechanisms of cytosolic DNA sensing by cGAS, STING and ALRs. Nature Reviews Immunology. [3] Pisetsky, D. S. (2016). The origin and properties of extracellular DNA: from basic science to self-antigen. Nature Reviews Rheumatology.

Other names

Cytosolic DNAExtranuclear DNAExogenous DNAPlasmidiDNA

Plasmid DNA serves as a template for the expression of therapeutic proteins or antigens within host cells. Intracellular DNA, particularly in the cytosol, acts as a ligand for pattern recognition receptors (PRRs) such as cyclic GMP-AMP synthase (cGAS) and Toll-like receptor 9 (TLR9), triggering the production of Type I interferons and pro-inflammatory cytokines through the STING pathway [1][2].