Aptamer antagonists of myelin promote axon growth
Myelin of the adult central nervous system (CNS) is one of the major sources of inhibition to axon regeneration following injury. The three known myelin-derived inhibitors (Nogo, MAG, and OMgp) bind with high affinity to the Nogo-66 receptor (NgR) on axons to limit neurite outgrowth. Here, we show that RNA aptamers can be generated that bind to NgR, compete with these inhibitors for binding to NgR, and promote axon elongation of neurons in vitro in the presence of these inhibitors. Aptamers have key advantages over protein antagonists, such as low cost and ease of production, high specificity and affinity for a wide range of targets, and simplicity with which they can be chemically modified to increase stability in vivo. The ability of aptamers to stimulate neurite elongation opens the possibility of reversing the inhibitory influence of CNS myelin via nucleic acid ligands.