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dc.contributor.authorLu, Yi
dc.contributor.authorTai, Phillip W. L.
dc.contributor.authorAi, Jianzhong
dc.contributor.authorGessler, Dominic J.
dc.contributor.authorSu, Qin
dc.contributor.authorYao, Xieyi
dc.contributor.authorZheng, Qiang
dc.contributor.authorZamore, Phillip D.
dc.contributor.authorXu, Xun
dc.contributor.authorGao, Guangping
dc.date2022-08-11T08:09:49.000
dc.date.accessioned2022-08-23T16:44:37Z
dc.date.available2022-08-23T16:44:37Z
dc.date.issued2018-03-02
dc.date.submitted2018-04-04
dc.identifier.citation<p>Mol Ther Nucleic Acids. 2018 Mar 2;10:349-360. doi: 10.1016/j.omtn.2017.12.019. Epub 2017 Dec 30. <a href="https://doi.org/10.1016/j.omtn.2017.12.019">Link to article on publisher's site</a></p>
dc.identifier.issn2162-2531 (Print)
dc.identifier.doi10.1016/j.omtn.2017.12.019
dc.identifier.pmid29499946
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40538
dc.description.abstractCorneal 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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=29499946&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rights© 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/).
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectadeno-associated virus
dc.subjectcorneal neovascularization
dc.subjectgene therapy
dc.subjectmiR-204
dc.subjectmicroRNA
dc.subjectEye Diseases
dc.subjectGenetics and Genomics
dc.subjectMolecular Biology
dc.subjectNucleic Acids, Nucleotides, and Nucleosides
dc.subjectTherapeutics
dc.subjectViruses
dc.titleTranscriptome Profiling of Neovascularized Corneas Reveals miR-204 as a Multi-target Biotherapy Deliverable by rAAVs
dc.typeJournal Article
dc.source.journaltitleMolecular therapy. Nucleic acids
dc.source.volume10
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4353&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/3342
dc.identifier.contextkey11902030
refterms.dateFOA2022-08-23T16:44:37Z
html.description.abstract<p>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.</p>
dc.identifier.submissionpathoapubs/3342
dc.contributor.departmentRNA Therapeutics Institute
dc.contributor.departmentDepartment of Microbiology and Physiological Systems
dc.contributor.departmentLi Weibo Institute for Rare Diseases Research
dc.contributor.departmentHorae Gene Therapy Center
dc.source.pages349-360


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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/).
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/).