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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE89538 | GEO | 2018/10/26

REPOSITORIES: GEO

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

Project description: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.

2018-10-26 | GSE89536 | GEO

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

2018-10-26 | GSE89537 | GEO

Transcriptome Profiling of Neovascularized Corneas Reveals miR-204 as a Multi-target Biotherapy Deliverable by rAAVs.

Project description: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.

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

Project description:Whole-transcriptome profiling of neovascularized corneas reveal miR-204 as a potent biotherapy deliverable by rAAVs

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A critical role of microRNAs in human pulmonary arterial hypertension. miR-204: a novel therapeutic target

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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Context-dependent miR-204 and miR-211 affect the biological properties of amelanotic and melanotic melanoma cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-03-26 | GSE94477 | GEO

A critical role of microRNAs in human pulmonary arterial hypertension. miR-204: a novel therapeutic target

Project description:This SuperSeries is composed of the SubSeries listed below.

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Project description:In this short report, we pinpoint some technical and conceptual flaws that we found in the article entitled "miR-204-5p and miR-211-5p contribute to BRAF inhibitor resistance in melanoma" (Díaz-Martínez et al., Cancer Research 2018). We also discuss how, in our opinion, these flaws led Díaz-Martínez and colleagues to incorrect conclusions about the biological role that miR-204 and miR-211 play in melanoma and about the terms of their involvement in the phenomenon of resistance to BRAF inhibitors.

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Whole-transcriptome gene expression profiling in TRPC1-silenced cells

Project description:This SuperSeries is composed of the SubSeries listed below.

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