The RNA revolution, advancing beyond traditional vaccines to new therapeutic modalities and constructs such as self-amplifying RNA (saRNA) and circular RNA (circRNA), continues to place increasing pressure on downstream purification. Diffusion-limited resins, the time-tested workhorse of protein purification, are fundamentally incompatible because mRNA is an enormous (>40 nm) molecule with low diffusivity (10−11–10−12 m2/s). Our perspective, rooted in core chemical engineering principles, applies transport analysis and re-examines published performance data to demonstrate why even optimized perfusion chromatographic resin systems, exhibiting 0.1 % of total flow through the resin particles, cannot overcome the inherent diffusional barriers preventing efficient RNA purification. Alternatively, convection-based devices, notably membranes and monoliths, are well situated as their transport characteristics are not limited by the molecular transport properties of RNA. Ultimately, pressure-driven flow enables the potential for increased device capacity at orders of magnitude (103x) lower process time and smaller device footprint contributing to markedly improved productivity. Taken together, these findings suggest that a paradigm shift is required toward convective membrane systems to create a platform capable of delivering scalable, economic, and ultimately industrially attractive mRNA purification.