Suprachoroidal delivery of viral and non-viral vectors for treatment of retinal and choroidal vascular diseases

Yeongseo Lim; Peter A Campochiaro; Jordan J Green

doi:10.1016/j.ajo.2024.12.010

Suprachoroidal delivery of viral and non-viral vectors for treatment of retinal and choroidal vascular diseases

Am J Ophthalmol. 2024 Dec 21:S0002-9394(24)00571-3. doi: 10.1016/j.ajo.2024.12.010. Online ahead of print.

Authors

Yeongseo Lim¹, Peter A Campochiaro², Jordan J Green³

Affiliations

¹ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University, Baltimore, MD.
² Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address: pcampo@jhmi.edu.
³ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University, Baltimore, MD; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD; Departments of Chemical & Biomolecular Engineering and Materials Science & Engineering, Johns Hopkins University, Baltimore, MD; Departments of Neurosurgery and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD; Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD. Electronic address: green@jhu.edu.

PMID: 39716546
DOI: 10.1016/j.ajo.2024.12.010

Abstract

Current treatments for retinal and choroidal neovascular diseases suffer from insufficient durability, including anti-vascular endothelial growth factor-A (VEGF-A) agents. It is, therefore, of interest to explore alternative methods that could allow for robust improvement in visual acuity with fewer injections required. Amongst various pre-clinical and clinical studies in the literature, a promising approach is the use of suprachoroidal injection with viral and non-viral gene delivery vectors. Compared to other ocular injection methods, suprachoroidal injection has demonstrated wide biodistribution of injected agents and safety as an outpatient procedure. In terms of viral vectors, suprachoroidal injection of an AAV8 vector expressing an anti-VEGF-A antibody fragment has shown an excellent safety profile and evidence of biological activity. In terms of non-viral vectors, lipid nanoparticles (LNPs) and polymeric nanoparticles (PNPs) are both demonstrating strong promise for ocular gene therapy in large animal models. In particular, biodegradable poly(beta-amino ester) (PBAE) nanoparticles show excellent biodistribution, safety, and efficacy for gene therapy via the suprachoroidal route. Non-viral nanoparticle approaches can have notable advantages over viral vectors in terms of carrying capacity, redosability, and manufacturing costs. An advantage of gene therapy is that once a delivery vector has been optimized, genetic cargos can be readily tailored without changing the safety, efficacy, and pharmacokinetic properties of the delivery vector. This review highlights recent progress that has been made and compares viral and non-viral suprachoroidal gene delivery for the treatment of retinal and choroidal vascular diseases. Suprachoroidal gene therapy is an emerging biotechnology that holds substantial potential to make a translational impact in treating these diseases.

Publication types

Editorial