RNA aptamers targeting AMPA receptors

RNA aptamers targeting AMPA receptors are an experimental, preclinical class of RNA-based antagonists designed to inhibit AMPA-type ionotropic glutamate receptors. Developed primarily by researchers at the University at Albany (SUNY) in collaboration with the University of Tokyo and Tokyo Medical University, these water-soluble oligonucleotides are isolated via SELEX (systematic evolution of ligands by exponential enrichment) and often chemically modified (e.g., with 2'-fluoro groups) to enhance ribonuclease resistance. The lead candidates, such as FN1040 and FN58, have been evaluated in mouse models of sporadic and familial amyotrophic lateral sclerosis (ALS), where they prevent motor neuron death, normalize TDP-43 pathology, and slow motor dysfunction by blocking excessive calcium influx mediated by unedited GluA2-containing AMPA receptors. This platform is also being explored for other central nervous system disorders involving excitotoxicity, such as neuropathic pain and epilepsy.