Dataset Information

AAV-PHP.eB transduces both the inner and outer retina with high efficacy in mice.

ABSTRACT: Recombinant adeno-associated virus (AAV) vectors are one of the main gene delivery vehicles used in retinal gene therapy approaches; however, there is a need to further improve the efficacy, tropism, and safety of these vectors. In this study, using a CMV-EGFP expression cassette, we characterize the retinal utility of AAV-PHP.eB, a serotype recently developed by in vivo directed evolution, which can cross the blood-brain barrier and target neurons with high efficacy in mice. Systemic and intravitreal delivery of AAV-PHP.eB resulted in the high transduction efficacy of retinal ganglion and horizontal cells, with systemic delivery providing pan-retinal coverage of the mouse retina. Subretinal delivery transduced photoreceptors and retinal pigment epithelium cells robustly. EGFP expression (number of transduced cells and mRNA levels) were similar when the retinas were transduced systemically or intravitreally with AAV-PHP.eB or intravitreally with AAV2/2. Notably, in photoreceptors, EGFP fluorescence intensities and mRNA levels were 50-70 times higher, when subretinal injections with AAV-PHP.eB were compared to AAV2/8. Our results demonstrate the pan-retinal transduction of ganglion cells and extremely efficient transduction of photoreceptor and retinal pigment epithelium cells as the most valuable features of AAV-PHP.eB in the mouse retina.

SUBMITTER: Palfi A

PROVIDER: S-EPMC9018541 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

AAV-PHP.eB transduces both the inner and outer retina with high efficacy in mice.

Palfi Arpad A Chadderton Naomi N Millington-Ward Sophia S Post Iris I Humphries Pete P Kenna Paul F PF Farrar G Jane GJ

Molecular therapy. Methods & clinical development 20220328

Recombinant adeno-associated virus (AAV) vectors are one of the main gene delivery vehicles used in retinal gene therapy approaches; however, there is a need to further improve the efficacy, tropism, and safety of these vectors. In this study, using a CMV-EGFP expression cassette, we characterize the retinal utility of AAV-PHP.eB, a serotype recently developed by <i>in vivo</i> directed evolution, which can cross the blood-brain barrier and target neurons with high efficacy in mice. Systemic and ...[more]

PMID: 35474956

Similar Datasets

Project description:Importance:In diabetic macular edema (DME), identification of baseline markers on spectral-domain optical coherence tomography (SD-OCT) and their association with severity of diabetic retinopathy (DR) might aid in disease management and the design of future trials. Objective:To examine associations between DR severity, retinal morphology on SD-OCT, and visual acuity in participants with DME. Design, Setting, and Participants:This cross-sectional observational case series was conducted at a single tertiary care referral center. Demographics, visual acuity, SD-OCT, and color fundus photographs of 80 individuals with DME (102 eyes) seen between December 28, 2013, and April 30, 2014, were analyzed between May 1 and July 31, 2016. Main Outcomes and Measures:Features captured on SD-OCT and thickness metrics. On SD-OCT we graded type and shape of DME, shape and presence of septae within the intraretinal cystoid abnormalities, presence of hyperreflective dots and foci, integrity of the external limiting membrane and ellipsoid zone, presence and extent of disorganization of the inner retinal layers (DRIL), and the status of the vitreomacular interface and epiretinal membrane. We measured retinal thickness at the fovea and at the site of maximum pathology, choroidal thickness at the fovea, and 1000 μm temporal and nasal to the fovea. Color photographs were graded to derive a DR severity stage. Results:The mean (SD) age was 63 (11) years, and 30 participants (37.5%) were women. The odds of having DRIL were greater in eyes with disrupted external limiting membrane (odds ratio [OR], 4.4; 95% CI, 1.6-12.0; P = .003), disrupted ellipsoid zone (OR, 2.7; 95% CI, 1.0-7.2; P = .03), presence of epiretinal membrane (OR, 2.8; 95% CI, 1.0-7.4; P = .03), and increase in retinal thickness at the fovea (OR, 1.6; 95% CI, 1.1-2.2; P < .001). Occurrence of DRIL was more likely in eyes with proliferative DR (OR, 7.3; 95% CI, 1.7-31.4; P = .007). Mean visual acuity decreased by approximately 4.7 letters for each 100-μm increase in the average global DRIL (95% CI, -7.9 to 1.4; P = .006). Conclusions and Relevance:An association was found between DRIL and disruption of the outer retina and increasing DR severity. Further longitudinal studies seem warranted to determine whether DRIL is a clinically relevant noninvasive morphological marker in eyes with DME.

Dataset Information

AAV-PHP.eB transduces both the inner and outer retina with high efficacy in mice.

Publications

AAV-PHP.eB transduces both the inner and outer retina with high efficacy in mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets