Reversible Cationic Glycopolymer Hydrogels for RNA Delivery in Ticks

Abstract

RNA interference (RNAi) offers a promising approach for vector control in species such as the lone star tick (Amblyomma americanum), but current delivery methods, including microinjection and soaking, are invasive and inefficient for large-scale application. In this work, we developed a series of novel physically cross-linked cationic glycopolymer hydrogels for noninvasive double-stranded RNA (dsRNA) delivery and evaluated their rheological properties, release behavior, and in vivo performance. Rheological characterization demonstrated shear-thinning and self-healing behavior conducive to sprayable applications, while release studies revealed tunable cargo delivery dependent on glycomonomer stereochemistry and cationic content. In vivo studies showed that cationic terpolymer hydrogels successfully traversed the peritrophic membrane and enabled tissue-specific gene silencing, including in ovarian tissue. These findings establish a promising platform for sprayable RNAi delivery and provide a framework for the design of targeted gene delivery systems.