Oligonucleotide therapeutics have advanced significantly over the past decades, yet progress remains limited by constraints in backbone chemistry. Current platforms primarily enable negatively charged or fully neutral backbones, restricting the ability to address key challenges such as cellular uptake, toxicity, and endosomal escape. Here, we present ZATA’s novel phosphotriester-based amidite platform, which expands the chemical toolbox without replacing existing technologies. This approach enables site-specific functionalization and programmable backbone engineering, including partial or complete charge neutralization or cationization. The platform preserves native nucleic acid properties while enhancing stability, delivery, and pharmacokinetics, offering a flexible and scalable path toward next-generation RNA therapeutics.