Model-Assisted Process Optimization for Trivalent Ligand-siRNA Conjugation via CuAAC Click Chemistry.

ABSTRACT: Small interfering RNA (siRNA) represents a potent gene therapy tool, playing pivotal roles in treating cancers and genetic disorders due to its unique advantages. Chemical modifications of nucleic acids serve as critical strategies to enhance the stability and targeting capability of RNA therapeutics, while overcoming siRNA delivery hurdles predominantly relies on covalent conjugation between targeting ligands and siRNA molecules. Among various macromolecular conjugation approaches, copper-catalyzed azide-alkyne cycloaddition (CuAAC) is widely adopted owing to its high reactivity, specificity, and biocompatibility. This study focuses on the systematic optimization of CuAAC click chemistry for synthesizing trivalent targeting ligand-RNA conjugates. Through design of experiments screening, f

SUBMITTER: Pan F 

PROVIDER: S-EPMC12593015 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature