RNA editing via adenosine-to-inosine (A-to-I) conversion requires adenosine deaminases acting on RNA (ADAR) and provides a reversible, transcript-level alternative to permanent DNA genome editing. Current strategies rely on the recruitment of endogenous human ADARs with synthetic guide RNAs (arRNAs, AIMers) instead of delivering exogenous Cas-fusion proteins, which reduces immunogenicity and delivery issues. There is a central paradox in this approach, because double-stranded RNA (dsRNA) is required for ADAR to catalyze deamination, but mammalian cells have evolved cytosolic sensors (e.g., MDA5, RIG-I, PKR, OAS/RNase L) and endosomal Toll-like receptors (TLR3, TLR7/8) specifically to detect and destroy dsRNA as a hallmark of viral infection. The guide-target duplexes used for editing thus have the potential to induce interferon production, translational arrest, or transcript degradation. This review discusses the overlapping structure of the editing demands of ADAR with the activation thresholds of immune sensors and summarizes chemical and topological evasion strategies. We discuss evidence that, although internal mismatches are deleterious, position-specific 2′-fluoro ribose modification, terminal dephosphorylation, distal base modification, and RNA circularization can support efficient editing while reducing innate immune activation. We also review delivery routes, off-target considerations, the clinical candidate WVE-006, and computational approaches to guide design.