Delivery of Antisense Oligonucleotides to the Cornea

Viet Q. Chau, Jiaxin Hu, Xin Gong, John D. Hulleman, Rafael L. Ufret-Vincenty, Frank Rigo, Thahza P. Prakash, David R. Corey, V. Vinod Mootha

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Antisense oligonucleotides (ASOs) are synthetic nucleic acids that recognize complementary RNA sequences inside cells and modulate gene expression. In this study, we explore the feasibility of ASO delivery to the cornea. We used quantitative polymerase chain reaction to test the efficacy of a benchmark ASO targeting a noncoding nuclear RNA, Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1), in a human corneal endothelial cell line, ex vivo human corneas, and in vivo in mice. In vivo delivery was via intravitreal or intracameral injections as well as topical administration. The anti-MALAT1 ASO significantly reduced expression of MALAT1 in a corneal endothelial cell line. We achieved a dose-dependent reduction of target gene expression in endothelial tissue from ex vivo human donor corneas. In vivo mouse experiments confirmed MALAT1 reduction in whole corneal tissue via intravitreal and intracameral routes, 82% and 71% knockdown, respectively (P < 0.001). Effects persisted up to at least 21 days, 32% (P < 0.05) and 43% (P < 0.05) knockdown, respectively. We developed protocols for the isolation and analysis of mouse corneal endothelium and observed reduction in MALAT1 expression upon both intravitreal and intracameral administrations, 64% (P < 0.05) and 63% (P < 0.05) knockdown, respectively. These data open the possibility of using ASOs to treat corneal disease.

Original languageEnglish (US)
Pages (from-to)207-214
Number of pages8
JournalNucleic Acid Therapeutics
Issue number4
StatePublished - Aug 2020


  • Fuchs' endothelial corneal dystrophy
  • cornea
  • corneal endothelium
  • oligonucleotide

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Drug Discovery


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