Whole-transcriptome profiling of neovascularized corneas reveal miR-204 as a potent biotherapy deliverable by rAAVs [RNA-Seq]

Current drugs that directly target pro-angiogenic factors to inhibit or reverse corneal neovascularization, the major sight-threatening pathology caused by angiogenic stimuli, require multiple rounds of administration and have limited efficacies. Here we report the profiling of anti-angiogenic corneal microRNAs (miRNAs), and a framework that employs discovered miRNAs as biotherapies deliverable by recombinant adeno-associated viruses (rAAVs). By querying differentially expressed miRNAs in neovascularized mouse corneas induced by alkali-burn, we have revealed 39 miRNAs that are predicted to target more than 5,500 differentially expressed corneal mRNAs. Among these corneal miRNAs, we selected miR-204 and assessed its efficacy as a therapeutic miRNA in injured corneas. Our results show that delivery of miR-204 by rAAV is efficacious and safe for mitigating corneal NV. Overall, our work demonstrates the discovery of therapeutic miRNAs in corneal disorders and their translation into viable clinical vectors. Overall design: Profiling of mRNAs in normal mouse corneas and corneas injured by alkali burn treatment.

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Lu Y, Tai PWL, Ai J, Gessler DJ, Su Q, Yao X, Zheng Q, Zamore PD, Xu X, Gao G