CRISPR-LbCpf1 prevents choroidal neovascularization in a mouse model of age-related macular degeneration

Taeyoung Koo, Sung Wook Park, Dong Hyun Jo, Daesik Kim, Jin Hyoung Kim, Hee Yeon Cho, Jeungeun Kim, Jeong Hun Kim, Jin Soo Kim

Research output: Contribution to journalArticlepeer-review

78 Citations (Scopus)

Abstract

LbCpf1, derived from Lachnospiraceae bacterium ND2006, is a CRISPR RNA-guided endonuclease and holds promise for therapeutic applications. Here we show that LbCpf1 can be used for therapeutic gene editing in a mouse model of age-related macular degeneration (AMD). The intravitreal delivery of LbCpf1, targeted to two angiogenesis-associated genes encoding vascular endothelial growth factor A (Vegfa) and hypoxia inducing factor 1a (Hif1a), using adeno-associated virus, led to efficient gene disruption with no apparent off-target effects in the retina and retinal pigment epithelium (RPE) cells. Importantly, LbCpf1 targeted to Vegfa or Hif1a in RPE cells reduced the area of laser-induced choroidal neovascularization as efficiently as aflibercept, an anti-VEGF drug currently used in the clinic, without inducing cone dysfunction. Unlike aflibercept, LbCpf1 targeted to Vegfa or Hif1a achieved a long-term therapeutic effect on CNV, potentially avoiding repetitive injections. Taken together, these results indicate that LbCpf1-mediated in vivo genome editing to ablate pathologic angiogenesis provides an effective strategy for the treatment of AMD and other neovascularization-associated diseases.

Original languageEnglish
Article number1855
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

Bibliographical note

Publisher Copyright:
© 2018 The Author(s).

Fingerprint

Dive into the research topics of 'CRISPR-LbCpf1 prevents choroidal neovascularization in a mouse model of age-related macular degeneration'. Together they form a unique fingerprint.

Cite this