Suprachoroidal Delivery of Viral and Nonviral Vectors for Treatment of Retinal and Choroidal Vascular Diseases.

PURPOSE: Current treatments for retinal and choroidal neovascular diseases suffer from insufficient durability, including anti-vascular endothelial growth factor-A agents. It is, therefore, of interest to explore alternative methods that could allow for robust improvement in visual acuity with fewer injections required.

DESIGN

Literature review.

RESULTS

Among various preclinical and clinical studies in the literature, a promising approach is the use of suprachoroidal injection with viral and nonviral gene delivery vectors. Compared with 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 adeno-associated virus 8 vector expressing an anti-vascular endothelial growth factor-A antibody fragment has shown an excellent safety profile and evidence of biological activity. In terms of nonviral vectors, lipid nanoparticles and polymeric nanoparticles both demonstrate strong promise for ocular gene therapy in large animal models. In particular, biodegradable poly(β-amino ester) nanoparticles show excellent biodistribution, safety, and efficacy for gene therapy via the suprachoroidal route. Nonviral 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.

CONCLUSIONS

This review highlights recent progress that has been made and compares viral and nonviral 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.