Key result
Two RNA aptamers isolated via SELEX demonstrated specific and high affinity (apparent KD~10 to 100 nM) for the NFAT DNA binding domain.
Effect estimate: KD~10 to 100 nM
The identification of specific RNA aptamers targeting the NFAT DNA binding domain provides a potential foundation for developing novel, less toxic immunosuppressive therapies.
Should not alter immunosuppression practice; hypothesis-generating for RNA aptamer tools targeting NFAT in future models.
Nuclear factor of activated T cells (NFAT) plays a central role in the immune response, and the immuno-suppressive drugs, cyclosporin A and FK-506, have been developed to inhibit it. However, due to the toxic effects of these drugs, which derive from their ability to inhibit calcineurin in non-immune tissues, the identification of small compounds that target NFAT directly could be an approach to developing less toxic immunosuppressive therapy. Using an in vitro selection technology termed SELEX on a combinatorial RNA library with 40 nucleotide-long random sequences, we have isolated two RNA aptamers to the NFAT DNA binding domain (DBD). Gel retardation assays and surface plasmon resonance measurements showed that the aptamers have a specific and high affinity (apparent KD~10 to 100 nM) for the NFAT DBD. Enzymatic probing analysis showed that the two RNA aptamers have similar structures and share a sequence that forms an apical loop. Moreover, RNase footprinting analysis showed that the shared sequence (GATATGAAGGA/ TGTG/AGAGAG) is critical for binding to both NFATp DBD and NFATc DBD. These results suggest that short RNAs identified in this study is a specific aptamer to NFAT DBD, and hence could be applied not only for the delineation of NFAT functions but for the development of potent immune modulating lead compounds.
No takes yet. Share an insight, caveat, or question.
Cho et al. (2004) studied this question. RNA aptamers to the NFAT DNA binding domain was evaluated on Affinity for the NFAT DNA binding domain (KD~10 to 100 nM). Two RNA aptamers isolated via SELEX demonstrated specific and high affinity (apparent KD~10 to 100 nM) for the NFAT DNA binding domain.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: