Brief intro:
- Author: Xiaoyu He, Yidian Fu, Yangfan Xu, Liang Ma, Peiwei Chai, Hanhan Shi, Yizheng Yao, Shengfang Ge, Renbing Jia, Xuyang Wen, Zhi Yang, Xianqun Fan
- Journal: Invest Ophthalmol Vis Sci
- Publication Date: 2025 Jan 2
Abstract
Purpose
This study aimed to identify a novel recombinant adeno-associated virus (rAAV) capsid variant that can widely transfect the deep retina through intravitreal injection and to assess their effectiveness and safety in gene delivery.
Methods
By adopting the sequences of various cell-penetrating peptides and inserting them into the capsid modification region of AAV2, we generated several novel variants. The green fluorescent protein (GFP)-carrying variants were screened following intravitreal injection. Gene therapy experiments were conducted via intravitreal injection of rd1 mice. We validated the therapeutic effects utilizing the pupillary light reflex and visual cliff test. Assessment of retinal structure and Pde6b gene levels in rd1 mice after gene therapy further was confirmed through transcriptome sequencing to validate the gene therapy efficacy.
Results
We observed enhanced transduction and penetration efficiency of the AAV variant AAV2.CPP.21 after intravitreal injection which can target all layers of the retinas. Normal doses of AAV2.CPP.21 administered via intravitreal injection achieved effective gene therapy for retinitis pigmentosa in rd1 mice, with no increased risk of transgenic leakage in peripheral organs.
Conclusions
Our study identified another new, safe, and efficient AAV vector for gene therapy via intravitreal injection for retinal diseases. This new vector holds promise for clinical application and improvement of the efficacy of gene therapy for inherited retinal diseases.
Keywords: AAV engineering, cell-penetrating peptides, intravitreal injection, retinitis pigmentosa
About PackGene
PackGene Biotech is a world-leading CRO and CDMO, excelling in AAV vectors, mRNA, plasmid DNA, and lentiviral vector solutions. Our comprehensive offerings span from vector design and construction to AAV, lentivirus, and mRNA services. With a sharp focus on early-stage drug discovery, preclinical development, and cell and gene therapy trials, we deliver cost-effective, dependable, and scalable production solutions. Leveraging our groundbreaking π-alpha 293 AAV high-yield platform, we amplify AAV production by up to 10-fold, yielding up to 1e+17vg per batch to meet diverse commercial and clinical project needs. Moreover, our tailored mRNA and LNP products and services cater to every stage of drug and vaccine development, from research to GMP production, providing a seamless, end-to-end solution.
