Suprachoroidal gene transfer with nonviral nanoparticles

Jikui Shen, Jayoung Kim, Stephany Y. Tzen, Kun Ding, Zibran Hafiz, Da Long, Jiangxia Wang, Jordan J. Gree, Peter A. Campochia

Research output: Contribution to journalArticlepeer-review

Abstract

Subretinal injections of viral vectors provide great benefits but have limited cargo capacity; they induce innate and adaptive immune responses, which may cause damage and preclude repeated injections; and they pose administration risks. As a new biotechnology, suprachoroidal injections of biodegradable nanoparticles (NPs) containing a reporter plasmid induce reporter expression in rat photoreceptors and RPE throughout the entire eye and maintain expression for at least 8 months. Multiple injections markedly increase expression. Suprachoroidal injection of NPs containing a VEGF expression plasmid caused severe subretinal neovascularization progressing to subretinal fibrosis, similar to what occurs in untreated patients with neovascular age-related macular degeneration, providing a new model and proof of concept for level and duration of expression. Suprachoroidal injection of NPs containing a VEGF-binding protein expression plasmid significantly suppressed VEGF-induced vascular leakage and neovascularization demonstrating therapeutic potential. These data suggest that nonviral NP suprachoroidal gene transfer may provide a noninvasive, repeatable alternative to subretinal injection of viral vectors.

Original languageEnglish (US)
Article numbereaba1606
JournalScience Advances
Volume6
Issue number27
DOIs
StatePublished - Jul 2020

ASJC Scopus subject areas

  • General

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