ArticleHuman gene therapy2023
The Degree of Adeno-Associated Virus-Induced Retinal Inflammation Varies Based on Serotype and Route of Delivery: Intravitreal, Subretinal, or Suprachoroidal.
Article in Human gene therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 27 citations in OpenAlex.
- Recovery of cone-mediated vision in Lebercilin associated retinal ciliopathy after gene therapy: One-year results of a phase I/II trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Trial
- mRNA delivery to the retina restores REP1 function in choroideremia.Molecular therapy. Advances · 2026Article
- AAV2 bypasses direct endosomal escape by using AAVR to access the trans-Golgi network en route to the nucleus.Journal of virology · 2026Article
- Development of a Targeted Choroidal Injury Model for the Study of Retinal Degenerations and Therapeutic Cell Replacement.Translational vision science & technology · 2026Article
- Modalities of vision restoration in optic neuropathies and retinal disease.Progress in retinal and eye research · 2026Review
- Article
- Gene therapy in patients with choroideremia: a meta-analysis of clinical trials.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Article
- Single-cell and spatial transcriptomic analyses of gene therapy-associated retinal inflammation in non-human primates.Molecular therapy. Advances · 2026Article
- Advances in RPGR gene therapy for X‑linked retinitis pigmentosa: From preclinical insights to clinical application (Review).International journal of molecular medicine · 2026Review
- Review
- Intravitreal AAV vector delivery induces integrin-dependent ocular inflammation, complement activation, and antiviral and DNA damage responses.Frontiers in immunology · 2026Article
- Production of clinical grade patient iPSC-derived 3D retinal organoids containing transplantable photoreceptor cells.Stem cell research & therapy · 2025Article
- Visual Neurorestoration: An Expert Review of Current Strategies for Restoring Vision in Humans.Brain sciences · 2025Review
- Retinal gene therapy using epiretinal AAV-containing fibrin hydrogel implants.Science advances · 2025Article
- Adeno-Associated Virus Vectors in Retinal Gene Therapy: Challenges, Innovations, and Future Directions.Biomolecules · 2025Review
- Adeno-associated viruses for efficient gene expression in the axolotl nervous system.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Characterization of the ocular inflammatory response to AAV reveals divergence by sex and age.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Intravitreal AAV2 gene delivery to feline retinal ganglion cells.Vision research · 2025Article
- Immune responses in retinal gene therapy: challenges, mechanisms, and future strategies.Frontiers in immunology · 2025Review
- Characterization of anti-AAV2 neutralizing antibody levels in sheep prior to and following intravitreal AAV2.7m8 injection.Gene therapy · 2024Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Adeno-associated virus (AAV)-mediated gene therapy has great potential for treating a wide range of retinal degenerative diseases. However, some initial enthusiasm for gene therapy has been tempered by emerging evidence of AAV-associated inflammation, which in several instances has contributed to clinical trial discontinuation. Currently, there is a paucity of data describing the variable immune responses to different AAV serotypes, and similarly, little is known regarding how these responses differ depending on route of ocular delivery, including in animal models of disease. In this study, we characterize the severity and retinal distribution of AAV-associated inflammation in rats triggered by delivery of five different AAV vectors (AAV1, AAV2, AAV6, AAV8, and AAV9), each of which contained enhanced green fluorescent protein (eGFP) driven under control of the constitutively active cytomegalovirus promoter. We further compare the inflammation across three different potential routes (intravitreal, subretinal, and suprachoroidal) of ocular delivery. Compared to buffer-injected controls for each route of delivery, AAV2 and AAV6 induced the most inflammation across all routes of delivery of vectors tested, with AAV6 inducing the highest levels of inflammation when delivered suprachoroidally. AAV1-induced inflammation was highest when delivered suprachoroidally, whereas minimal inflammation was seen with intravitreal delivery. In addition, AAV1, AAV2, and AAV6 each induce infiltration of adaptive immune cells like T cells and B cells into the neural retina, suggesting an innate adaptive response to a single dose of virus. AAV8 and AAV9 induced minimal inflammation across all routes of delivery. Importantly, the degree of inflammation was not correlated with vector-mediated transduction and expression of eGFP. These data emphasize the importance of considering ocular inflammation when selecting AAV serotypes and ocular delivery routes for the development of gene therapy strategies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.