Transcriptome Profiling of Neovascularized Corneas Reveals miR-204 as a Multi-target Biotherapy Deliverable by rAAVs
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Authors
Lu, YiTai, Phillip W. L.
Ai, Jianzhong
Gessler, Dominic J.
Su, Qin
Yao, Xieyi
Zheng, Qiang
Zamore, Phillip D.
Xu, Xun
Gao, Guangping
UMass Chan Affiliations
RNA Therapeutics InstituteDepartment of Microbiology and Physiological Systems
Li Weibo Institute for Rare Diseases Research
Horae Gene Therapy Center
Document Type
Journal ArticlePublication Date
2018-03-02Keywords
adeno-associated viruscorneal neovascularization
gene therapy
miR-204
microRNA
Eye Diseases
Genetics and Genomics
Molecular Biology
Nucleic Acids, Nucleotides, and Nucleosides
Therapeutics
Viruses
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Show full item recordAbstract
Corneal neovascularization (NV) is the major sight-threatening pathology caused by angiogenic stimuli. Current drugs that directly target pro-angiogenic factors to inhibit or reverse the disease require multiple rounds of administration and have limited efficacies. Here, we identify potential anti-angiogenic corneal microRNAs (miRNAs) and demonstrate 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, we selected miR-204 and assessed its efficacy and therapeutic benefit for treating injured corneas. Our results show that delivery of miR-204 by rAAV normalizes multiple novel target genes and biological pathways to attenuate vascularization of injured mouse cornea. Importantly, this gene therapy treatment alternative is efficacious and safe for mitigating corneal NV. Overall, our work demonstrates the discovery of potential therapeutic miRNAs in corneal disorders and their translation into viable treatment alternatives.Source
Mol Ther Nucleic Acids. 2018 Mar 2;10:349-360. doi: 10.1016/j.omtn.2017.12.019. Epub 2017 Dec 30. Link to article on publisher's site
DOI
10.1016/j.omtn.2017.12.019Permanent Link to this Item
http://hdl.handle.net/20.500.14038/40538PubMed ID
29499946Related Resources
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© 2018 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Distribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1016/j.omtn.2017.12.019
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Except where otherwise noted, this item's license is described as © 2018 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).