DNAzyme targeting RIP3 suppresses NLRP3-mediated necroinflammation for the treatment of inflammatory diseases.

ABSTRACT: Necroptosis, a form of programmed cell death, initiates a series of biological responses and further culminates in necroinflammatory processes, consequently limiting the efficacy of cytokine antagonists in treating inflammatory diseases. To address this issue, DNAzyme R3-Dz specifically targeting receptor-interacting protein kinase 3 (RIP3) mRNA, a necrosome component, has been successfully developed and studied to elucidate the mechanism in cleaving its target mRNA. Then a polyamidoamine (PAMAM) derivative was constructed through the modification of nucleobase analog (termed AP) to achieve the R3-Dz delivery to macrophages. The AP/R3-Dz nanoparticles effectively downregulated the RIP3 expression, leading to subsequent decrease in the levels of reactive oxygen species (ROS) and damage-asso

SUBMITTER: Jia J 

PROVIDER: S-EPMC12648105 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature