» Articles » PMID: 37221271

Tolerability and Tropism of Recombinant Adeno-associated Virus Vectors in the African Green Monkey (Chlorocebus Sabaeus) Anterior Chamber

Overview
Journal Gene Ther
Date 2023 May 23
PMID 37221271
Authors
Affiliations
Soon will be listed here.
Abstract

While many studies have investigated the use of recombinant adeno-associated vectors (rAAV) in the posterior chamber for treatment of inherited retinal diseases, fewer studies have looked at rAAV's ability to transduce cells within the anterior chamber. This study focuses on evaluating the tropism and tolerability of three rAAV serotypes-rAAV2/6, rAAV2/9, and rAAV2/2[MAX]-expressing a green fluorescent protein (GFP) reporter following intracameral injection in the non-human primate (NHP) African green monkey (Chlorocebus sabaeus) model. Injection of high dose (1 × 10 vg/eye) rAAV vector resulted in transient inflammation characterized by aqueous flare and cellular infiltrate that resolved without intervention in all serotypes. Post-mortem histology revealed widespread expression of GFP in cells of the trabecular meshwork and iris in high dose rAAV2/6, rAAV2/9, and particularly rAAV2/2[MAX] eyes, indicating that rAAV vectors of these serotypes have broad tropism for cells of the anterior chamber and may facilitate the treatment of blinding disorders, such as glaucoma.

References
1.
Pascolini D, Mariotti S . Global estimates of visual impairment: 2010. Br J Ophthalmol. 2011; 96(5):614-8. DOI: 10.1136/bjophthalmol-2011-300539. View

2.
Morgan J, Murphy C, Russell P . What do mechanotransduction, Hippo, Wnt, and TGFβ have in common? YAP and TAZ as key orchestrating molecules in ocular health and disease. Exp Eye Res. 2013; 115:1-12. PMC: 3795947. DOI: 10.1016/j.exer.2013.06.012. View

3.
Kay C, Ryals R, Aslanidi G, Min S, Ruan Q, Sun J . Targeting photoreceptors via intravitreal delivery using novel, capsid-mutated AAV vectors. PLoS One. 2013; 8(4):e62097. PMC: 3637363. DOI: 10.1371/journal.pone.0062097. View

4.
Mohan R, Schultz G, Hong J, Mohan R, Wilson S . Gene transfer into rabbit keratocytes using AAV and lipid-mediated plasmid DNA vectors with a lamellar flap for stromal access. Exp Eye Res. 2003; 76(3):373-83. DOI: 10.1016/s0014-4835(02)00275-0. View

5.
Rodriguez-Estevez L, Asokan P, Borras T . Transduction optimization of AAV vectors for human gene therapy of glaucoma and their reversed cell entry characteristics. Gene Ther. 2019; 27(3-4):127-142. PMC: 7153980. DOI: 10.1038/s41434-019-0105-4. View