Crystal Structure of Autotaxin Complexed with Inhibitory DNA Aptamer and Development of Treatment for Lung Fibrosis

Abstract

Autotaxin is a plasma lysophospholipase D that hydrolyzes lysophosphatidylcholine to produce lysophosphatidic acid, and attractive target for treatment of Lung fibrosis. We developed anti- autotaxin DNA aptamers that inhibit autotaxin with high specificity and efficacy. We determined the crystal structure of autotaxin complexed with the anti-autotaxin aptamer RB011, and revealed the structural basis for the specific inhibition of autotaxin by the anti-autotaxin aptamer. We optimized RB011 based on the structural information to further improve its in vivo efficacy.