Clinical and Ocular Inflammatory Inhibitors of Viral-Based Gene Therapy of the Retina
Abstract
:1. Introduction
1.1. Vector Types
1.2. Routes of Delivery
1.3. Mechanism of Inflammation
1.4. Inflammatory Response Based on Delivery Method
2. Current Applications
2.1. Clinical Trials
2.2. Ocular Inflammation Management
3. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Intravitreal | Subretinal | Suprachoroidal | |
---|---|---|---|
Advantages | •Clinic administered | •Minimal humoral response | •Clinic administration |
•Diffuse treatment of entire retina | •ACAID promoting immune tolerance | •Better exposure to outer retina/RPE | |
•Able to reach outer retina/RPE | •Limits intraocular exposure and outflow through trabecular meshwork | ||
•Diffuse treatment of entire retina | |||
Disadvantages | •Greater systemic exposure and humoral response | •Requires surgical instillation | •Few trials |
•The highest potential for intraocular inflammation | •Surgical complications | •Possibly shorter duration of effect | |
•Retinal thinning and hyperreflective foci | •Newer, less familiar technique | ||
•Focal treatment | •Risk of subretinal injection |
NCT Number | Phase | Condition | Gene/Genetic Material Delivered | Drug | Vector/Molecule | Route | Status |
---|---|---|---|---|---|---|---|
NCT04418427 | 2 | Diabetic Macular Edema, Diabetic Retinopathy | aflibercept | AAV.7m8-aflibercept | AAV2 | Intravitreal | Complete |
NCT05536973 | 2 | nAMD | aflibercept | AAV.7m8-aflibercept | AAV2 | Intravitreal | Active |
NCT05158296 | 2/3 | Retinitis Pigmentosa, Usher Syndrome | USH2A | Ultevursen | antisense RNA oligonucleotide | Intravitreal | Active |
NCT03780257 | 1/2 | Retinitis Pigmentosa, Usher Syndrome | USH2A | QR-421a | antisense RNA oligonucleotide | Intravitreal | Complete |
NCT03293524 | 3 | LHON | ND4 | GS010 (rAAV2/2-ND4) | AAV2 | Intravitreal | Active |
NCT03140969 | 1/2 | LCA | CEP290 | QR-110 | antisense RNA oligonucleotide | Intravitreal | Complete |
NCT02652780 | 3 | LHON | ND4 | GS010 (rAAV2/2-ND4) | AAV2 | Intravitreal | Complete |
NCT03406104 | 3 | LHON | ND4 | GS010 (rAAV2/2-ND4) | AAV2 | Intravitreal | Complete |
NCT04945772 | 2 | Retinitis Pigmentosa | MCO-010 | MC0-010 | AAV2 | Intravitreal | Complete |
(optogenetic) | |||||||
NCT02161380 | 1 | LHON | ND4 | scAAV2-P1ND4v2 | AAV2 | Intravitreal | Active |
NCT04919473 | 1/2 | Retinitis Pigmentosa | vMCO-I | vMCO-I | AAV2 | Intravitreal | Complete |
NCT05417126 | 2 | Stargardt Disease | vMCO-010 | vMCO-010 | AAV2 | Intravitreal | Complete |
(optogenetic) | |||||||
NCT05293626 | 1/2 | LHON | ND4 | NR082 (rAAV2-ND4) | AAV2 | Intravitreal | Active |
NCT04123626 | 1/2 | Autosomal Dominant Retinitis Pigmentosa (P23H) | RHO | QR-1123 | antisense RNA oligonucleotide | Intravitreal | Active |
NCT03748784 | 1 | nAMD | aflibercept | AAV.7m8-aflibercept | AAV2 | Intravitreal | Complete |
NCT03913143 | 2/3 | LCA | CEP290 | QR-110 | antisense RNA oligonucleotide | Intravitreal | Active |
NCT02652767 | 3 | LHON | ND4 | GS010 (rAAV2/2-ND4) | AAV2 | Intravitreal | Complete |
NCT04483440 | 1 | Choroideremia | CHM | 4D-110 | AAV2 | Intravitreal | Active |
NCT02317887 | 1/2 | X-Linked Retinoschisis | RS1 | AAV8-scRS/IRBPhRS | AAV8 | Intravitreal | Active |
NCT02556736 | 1/2 | Retinitis Pigmentosa | ChR2 | RST-001 | AAV2 | Intravitreal | Active |
NCT03066258 | 1/2 | nAMD | Anti-VEGF monoclonal antibody fragment | RGX-314 | AAV8 | Intravitreal | Complete |
NCT03144999 | 1 | Dry AMD | sCD59 | AAVCAGsCD59 | AAV2 | Intravitreal | Complete |
NCT03153293 | 2/3 | LHON | G11778A ND4 | rAAV2-ND4 | AAV2 | Intravitreal | Active |
NCT03585556 | 1 | nAMD | sCD59 | AAVCAGsCD59 | AAV2 | Intravitreal | Complete |
NCT01024998 | 1 | nAMD | sFLT01 | AAV2-sFLT01 | AAV2 | Intravitreal | Complete |
NCT06196827 | 1/2 | LCA | RPE65 | LX101 (rAAV2-RPE65) | AAV2 | Subretinal | Active |
NCT06300476 | 1/2 | Stargardt Disease | ABCA4 | JWK006 | AAV hybrid | Subretinal | Active |
NCT03278873 | 1/2 | Achromatopsia | CNGB3 | AAV2/8-hCARp.hCNGB3 | AAV2 | Subretinal | Complete |
CNGA3 | AAV2/8-hG1.7p.coCNGA3 | ||||||
NCT00749957 | 1/2 | LCA | RPE65 | rAAV2-CB-hRPE65 | AAV2 | Subretinal | Complete |
NCT03374657 | 1/2 | Retinitis Pigmentosa | RLBP1 | CPK850 (scAAV8-RLBP1) | AAV8 | Subretinal | Active |
NCT02599922 | 1/2 | Achromatopsia | CNGB3 | AGTC-401 (rAAV2tYF-PR1.7-hCNGB3) | AAV2 | Subretinal | Active |
NCT02671539 | 2 | Choroideremia | REP1 | rAAV2.REP1 | AAV2 | Subretinal | Complete |
NCT02553135 | 2 | Choroideremia | REP1 | AAV2-REP1 | AAV2 | Subretinal | Complete |
NCT02781480 | 1/2 | LCA | RPE65 | AAV2/5-OPTIRPE65 | AAV2/5 | Subretinal | Complete |
NCT02610582 | 1/2 | Achromatopsia | CNGA3 | rAAV.hCNGA3 | AAV8 | Subretinal | Active |
NCT04516369 | 3 | LCA | RPE65 | voretigene neparvovec-rzyl (AAV2-hRPE65v2) | AAV2 | Subretinal | Active |
NCT00481546 | 1 | LCA | RPE65 | rAAV2-CBSB-hRPE65 | AAV2 | Subretinal | Active |
NCT03001310 | 1/2 | Achromatopsia | CNGB3 | AAV2/8-hCARp.hCNGB3 | AAV2/8 | Subretinal | Complete |
NCT01496040 | 1/2 | LCA | RPE65 | rAAV-2/4.hRPE65 | AAV2/4 | Subretinal | Complete |
NCT00821340 | 1 | LCA | RPE65 | rAAV2-hRPE65 | AAV2 | Subretinal | Complete |
NCT05791864 | 1/2 | CLN2 (Batten disease) | TPP1 | RGX-381 (AAV9.CB7.hCLN2) | AAV9 | Subretinal | Active |
NCT03748784 | 1 | nAMD | Aflibercept | ADVM-022 (AAV.7m8-aflibercept) | AAV2 | Subretinal | Complete |
NCT03872479 | 1/2 | LCA | CEP290 | EDIT-101 | CRISPR/Cas9 therapy | Subretinal | Active |
NCT01482195 | 1 | Retinitis Pigmentosa | MERTK | rAAV2-VMD2-hMERTK | AAV2 | Subretinal | Complete |
NCT04611503 | 1/2 | Retinitis Pigmentosa | PDE6A | rAAV.hPDE6A | AAV2/8 | Subretinal | Active |
NCT01301443 | 1 | nAMD | Endostatin and angiostatin | Retinostat | lentiviral | Subretinal | Complete |
NCT04794101 | 3 | X-Linked Retinitis Pigmentosa | RPGR | AAV5-hRKp.RPGR | AAV5 | Subretinal | Active |
NCT03758404 | 1/2 | Achromatopsia | CNGA3 | AAV2/8-hG1.7p.coCNGA3 | AAV2/8 | Subretinal | Complete |
NCT00999609 | 3 | LCA | RPE65 | voretigene neparvovec-rzyl (AAV2-hRPE65v2) | AAV2 | Subretinal | Active |
NCT04832724 | 2 | nAMD | Anti-VEGF-A antigen binding fragment | RGX-314 | AAV8 | Subretinal | Complete |
NCT01461213 | 1/2 | Choroideremia | REP1 | rAAV.REP1 | AAV2 | Subretinal | Complete |
NCT03585556 | 1 | nAMD | sCD59 | AAVCAGsCD59 | AAV2 | Subretinal | Complete |
NCT02341807 | 1/2 | Choroideremia | CHM | AAV2-hCHM | AAV2 | Subretinal | Complete |
NCT02407678 | 2 | Choroideremia | REP1 | AAV2.REP1 | AAV2 | Subretinal | Complete |
NCT02935517 | 1/2 | Achromatopsia | CNGA3 | AGTC-402 (rAAV2tYF-PR1.7-hCNGA3) | AAV2 | Subretinal | Active |
NCT02077361 | 1/2 | Choroideremia | REP1 | rAAV2.REP1 | AAV2 | Subretinal | Complete |
NCT01494805 | 1/2 | nAMD | sFlt-1 | rAAV.sFlt-1 | AAV2 | Subretinal | Complete |
NCT00516477 | 1 | LCA | RPE65 | voretigene neparvovec-rzyl (AAV2-hRPE65v2) | AAV2 | Subretinal | Complete |
NCT01024998 | 1 | nAMD | sFLT01 | AAV2-sFLT01 | AAV2 | Subretinal | Complete |
NCT00643747 | 1/2 | LCA | RPE65 | rAAV2/2.hRPE65p.hRPE65 | AAV2 | Subretinal | Complete |
NCT03252847 | 1/2 | X-Linked Retinitis Pigmentosa | RPGR | AAV2/5-RPGR | AAV2/5 | Subretinal | Complete |
RPE | Photoreceptors | Ganglion Cells | nAbs | Additional Notes | |
---|---|---|---|---|---|
AAV1 | Yes | No | No | +++ | |
AAV2 | Yes | Yes | Yes | ++++ | Brain transduction |
AAV4 | Yes | No | No | Unk | |
AAV5 | Yes | No | No | + | |
AAV6 | Yes | No | No | ++ | |
AAV8 | Yes | Yes | No | + | |
AAV9 | Yes | No | No | + | Systemic transduction |
Hybrid | Yes | Yes | Yes | Low |
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© 2024 by the authors. Published by MDPI on behalf of the Hellenic Society for Microbiology. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ohlhausen, M.; Conrady, C.D. Clinical and Ocular Inflammatory Inhibitors of Viral-Based Gene Therapy of the Retina. Acta Microbiol. Hell. 2024, 69, 187-203. https://doi.org/10.3390/amh69030018
Ohlhausen M, Conrady CD. Clinical and Ocular Inflammatory Inhibitors of Viral-Based Gene Therapy of the Retina. Acta Microbiologica Hellenica. 2024; 69(3):187-203. https://doi.org/10.3390/amh69030018
Chicago/Turabian StyleOhlhausen, Marc, and Christopher D. Conrady. 2024. "Clinical and Ocular Inflammatory Inhibitors of Viral-Based Gene Therapy of the Retina" Acta Microbiologica Hellenica 69, no. 3: 187-203. https://doi.org/10.3390/amh69030018