Translational opportunities in aptamer and nanobody lateral flow assays within the WHO REASSURED framework.

Abstract

The World Health Organization's REASSURED framework underscores the role of lateral flow assays (LFAs) in addressing diagnostic access gaps in low-resource regions affected by emerging and re-emerging pathogens, neglected tropical diseases, and diseases of unknown etiology. While antibody-based LFAs dominate clinical use, aptamers and nanobodies have emerged as alternative recognition elements with favorable stability, reproducibility, and manufacturing characteristics. This review examines the analytical performance of aptamer- and nanobody-based LFAs across infectious and immune-mediated disease contexts and situates these systems within the diagnostic development landscape. Across disease settings, analytically robust performance comparable to antibody-based formats is routinely demonstrated under controlled conditions. However, comparative analysis reveals a persistent disconnect between analytical feasibility and progression into standardized clinical validation and deployment. Translational outcomes are more often constrained by specimen access, comparator definition, manufacturing readiness, and regulatory precedent than by limitations in binder affinity or assay chemistry. These findings indicate that for researchers developing next-generation LFAs, analytical optimization alone is insufficient; successful translation increasingly depends on alignment with validation, manufacturing, and deployment frameworks that govern diagnostic evaluation.