Topical Use of Angiopoietin-like Protein 2 RNAi-loaded Lipid Nanoparticles Suppresses Corneal Neovascularization | Zendy

Y. Taketani | Zendy; Tomohiko Usui | Zendy; Tetsuya Toyono | Zendy; Nobuyuki Shima | Zendy; Seiichi Yokoo | Zendy; Mikiko Kimakura | Zendy; Satoru Yamagami | Zendy; Shinichiro Ohno | Zendy; Risako Onodera | Zendy; Kohei Tahara | Zendy; Hirofumi Takeuchi | Zendy; Masahiko Kuroda | Zendy

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Topical Use of Angiopoietin-like Protein 2 RNAi-loaded Lipid Nanoparticles Suppresses Corneal Neovascularization

Author(s) -

Y. Taketani,

Tomohiko Usui,

Tetsuya Toyono,

Nobuyuki Shima,

Seiichi Yokoo,

Mikiko Kimakura,

Satoru Yamagami,

Shinichiro Ohno,

Risako Onodera,

Kohei Tahara,

Hirofumi Takeuchi,

Masahiko Kuroda

Publication year - 2016

Publication title -

molecular therapy — nucleic acids

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.208

H-Index - 59

ISSN - 2162-2531

DOI - 10.1038/mtna.2016.1

Subject(s) - cornea , corneal neovascularization , small hairpin rna , stroma , chemistry , angiogenesis , neovascularization , rna , microbiology and biotechnology , biochemistry , biology , cancer research , ophthalmology , medicine , immunology , immunohistochemistry , gene

Corneal neovascularization (CNV) is a sight-threatening condition that is encountered in various inflammatory settings including chemical injury. We recently confirmed that angiopoietin-like protein 2 (ANGPTL2) is a potent angiogenic and proinflammatory factor in the cornea, and we have produced a single-stranded proline-modified short hairpin anti-ANGPTL2 RNA interference molecule that is carried in a lipid nanoparticle (ANGPTL2 Li-pshRNA) for topical application. In this study, we have further examined the topical delivery and anti-ANGPTL2 activity of this molecule and have found that fluorescence-labeled ANGPTL2 Li-pshRNA eye drops can penetrate all layers of the cornea and that ANGPTL2 mRNA expression was dramatically inhibited in both epithelium and stroma at 12 and 24 hours after administration. We also examined the inhibitory effect of ANGPTL2 Li-pshRNA on CNV in a mouse chemical injury model and found that the area of angiogenesis was significantly decreased in corneas treated with ANGPTL2 Li-pshRNA eye drops compared to controls. Together, these findings indicate that this modified RNA interference agent is clinically viable in a topical formulation for use against CNV

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