Aptamers as immunomodulatory therapeutic alternatives targeting neglected tropical diseases (NTDs).

Neglected tropical diseases (NTDs) comprise a heterogeneous group of infections that disproportionately affect populations in low- and middle-income countries, where limited access to diagnostics, therapeutics, and surveillance perpetuates disease burden. Conventional strategies based on antibodies and small-molecule drugs face major challenges, including high production costs, limited stability, cross-reactivity, toxicity, and the emergence of drug resistance. In this context, aptamers, short single-stranded nucleic acids selected by SELEX, have emerged as versatile immunomodulatory tools with significant potential for the diagnosis and treatment of NTDs. This chapter provides a comprehensive overview of aptamer-based strategies targeting major NTDs, with particular emphasis on human African trypanosomiasis and arboviral infections such as dengue, Zika, and chikungunya. Aptamers directed against conserved parasite and viral epitopes demonstrate the capacity to circumvent immune evasion mechanisms, including antigenic variation and serotype diversity, while enabling highly specific recognition and internalization. In African trypanosomes, RNA aptamers targeting variant surface glycoproteins exploit the flagellar pocket for targeted drug delivery, offering a novel approach to overcome therapeutic resistance. In arboviral diseases, aptamers have been successfully integrated into advanced diagnostic platforms, including competitive ELISA, electrochemical, and capacitive biosensors, achieving high sensitivity, rapid response times, and minimal cross-reactivity among closely related flaviviruses. Beyond diagnostics, selected aptamers exhibit neutralizing activity and immunomodulatory effects by interfering with host-pathogen interactions and innate immune signaling pathways.