Tolerability and tropism of recombinant adeno-associated virus vectors in the African green monkey (Chlorocebus sabaeus) anterior chamber. Gene Ther 2023 Sep;30(9):714-722
Date
05/24/2023Pubmed ID
37221271DOI
10.1038/s41434-023-00407-zScopus ID
2-s2.0-85160260133 (requires institutional sign-in at Scopus site)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 × 1012 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.
Author List
Chern KJ, Issac KZ, Gumbs ZD, O'Connor ME, Lawrence MS, Lipinski DMAuthor
Daniel M. Lipinski PhD Associate Professor in the Ophthalmology and Visual Sciences department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAnterior Chamber
Dependovirus
Genetic Vectors
Transduction, Genetic
Tropism