Adeno-associated virus mediated gene therapy for retinal degenerative diseases

Methods: A rAAV carrying the enhanced green fluorescent protein gene driven by a cytomegalovirus promoter was produced by either co-infecting the cell line with E1-defective adenovirus and purified by CsCl 2 density gradient CsCl 2 -rAAV , or by transfecting with an adenoviral helper plasmid and purified by iodixanol density gradient followed by heparin column chromatography heparin-rAAV.

The impact of different virus preparations on the patterns of transgene expression was investigated after subretinal injection. Subretinal injection of either rAAV preparation induced no changes to retinal morphology and retinal-choroidal vasculature. Preclinical evaluation of ADVM, a novel gene therapy approach to treating wet age-related macular degeneration.

Long-term safety evaluation of continuous intraocular delivery of aflibercept by the intravitreal gene therapy candidate ADVM in nonhuman primates. Transl Vis Sci Technol. J Ocul Pharm Ther. Mol Ther Methods Clin Dev. Biotechnologies A. Retinal Physician. Accessed 1 Apr Bahadorani S, Singer M. Recent advances in the management and understanding of macular degeneration. Drusen complement components C3a and C5a promote choroidal neovascularization. Am J Ophthalmol. Functional expression of complement factor I following AAV-mediated gene delivery in the retina of mice and human cells.

Waheed NK. Presented virtually at Angiogenesis, Exudation, and Degeneration Protective responses to sublytic complement in the retinal pigment epithelium. Accessed 20 Aug Duker JS. Subretinal injection: A review on the novel route of therapeutic delivery for vitreoretinal diseases. Ophthalmic Res. Suprachoroidal and subretinal injections of AAV using transscleral microneedles for retinal gene delivery in nonhuman primates.

A subretinal cell delivery method via suprachoroidal access in minipigs: Safety and surgical outcomes. The suprachoroidal space: from potential space to a space with potential. Choroidal changes after Suprachoroidal Injection of Triamcinolone Acetonide in eyes with macular edema secondary to Retinal Vein Occlusion. Emami-Naeini P, Yiu G. Medical and surgical applications for the suprachoroidal space. Int Ophthalmol Clin. Characterization of the choroid-scleral junction and suprachoroidal layer in healthy individuals on enhanced-depth imaging optical coherence tomography.

JAMA Ophthalmol. AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression. J Clin Investig. Suprachoroidal gene transfer with nonviral nanoparticles. Sci Adv. Host immune responses after suprachoroidal delivery of AAV8 in nonhuman primate eyes. Ocular inflammation and treatment emergent adverse events in retinal gene therapy. Differential activation of innate immune responses by adenovirus and adeno-associated virus vectors.

Unraveling the complex story of immune responses to AAV vectors trial after trial. Europe PMC requires Javascript to function effectively.

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Abstract Available from publisher site using DOI. A subscription may be required. Stieger K ,. Therese Cronin Search articles by 'Therese Cronin'.

Cronin T ,. Jean Bennett Search articles by 'Jean Bennett'. Bennett J ,. Fabienne Rolling Search articles by 'Fabienne Rolling'. Affiliations All authors 1. Share this article Share with email Share with twitter Share with linkedin Share with facebook. Abstract Retinal gene therapy holds great promise for the treatment of inherited and noninherited blinding diseases such as retinitis pigmentosa and age-related macular degeneration. The most widely used vectors for ocular gene delivery are based on adeno-associated virus AAV because it mediates long-term transgene expression in a variety of retinal cell types and elicits minimal immune responses.

Inherited retinal diseases are nonlethal and have a wide level of genetic heterogeneity. Many of the genes have now been identified and their function elucidated, providing a major step towards the development of gene-based treatments. Extensive preclinical evaluation of gene transfer strategies in small and large animal models is key to the development of successful gene-based therapies for the retina.

These preclinical studies have already allowed the field to reach the point where gene therapy to treat inherited blindness has been brought to clinical trial. Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative.

Advanced search. Skip to main content Thank you for visiting nature. Download PDF. Subjects Drug development Targeted gene repair. References 1. Article Google Scholar 9. Acknowledgements The authors thank Ms. Jayandharan Authors Shubham Maurya View author publications.

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