Nanotechnology Lighting the Way for Gene Therapy in Ophthalmopathy: From Opportunities toward Applications
Abstract
:1. Introduction
2. Classifications and Injection Schemes of NADs in Gene Therapy for Ophthalmopathy
2.1. Common NAD Types in Gene Therapy for Ophthalmopathy
2.2. Gene Selection Options of NADs in Gene Therapy for Ophthalmopathy
2.3. Diverse Delivery Strategies Overcoming Delivery Efficiency in Ophthalmopathy
3. The Application of Nanotechnology in Gene Therapy Can Help Improve Treatment
3.1. NAD Carriers in Gene Therapy for Eye Diseases
Carrier | Advantages | Disadvantages | Target Tissue | References |
---|---|---|---|---|
Lentiviral carrier | Wide range of target cells and strong ability to carry foreign genes | Carcinogenic risk | Retinal ganglion cells, lens epithelial cells, corneal epithelial cells | [74,75,76] |
Adenovirus carrier | Short expression time, High expression level of foreign genes | Strong immunogenicity | Photoreceptor cells, retinal pigment epithelial cells | [77] |
Adeno-associated virus carrier | High infection efficiency | Strong immunogenicity | Photoreceptor cells, retinal pigment epithelial cells, retinal ganglion cells, lens epithelial cells | [78,79] |
Nonviral Carrier | Advantages | Disadvantages | Target Tissue | References |
---|---|---|---|---|
Cationic lipid carrier | Increasing the local retention time of drugs, slow release of drugs, improving the bioavailability of drugs | Low transfection efficiency | Cornea, bulbar conjunctiva, sclera, retina, | [81,82] |
Cationic polymer | Beneficial to endocytosis and will not be degraded by enzymes | High cytotoxicity | Retina | [83] |
Lipid nanoparticles | High sustained release, high stability and low toxicity | Low transfection efficiency and hard to store | Cornea, retina | [84,85] |
Inorganic nanoparticles | Easy to decorate, versatile | Poor biocompatibility | Cornea, retina | [86] |
3.2. Nanocarriers Can Improve the Targeting and Biological Distribution of NADs in the Eyes
3.3. Using Nanotechnology to Improve the Stability of NADs to Overcome Drug Instability
4. The Mechanisms and Advantages of NADs in Gene Therapy for Ophthalmopathy
4.1. Principles and Advantages of Using cDNA as Therapeutic Nucleic Acid
4.2. Principles and Advantages of Using Small Interfering RNA (siRNA) as Therapeutic Nucleic Acid
4.3. Principles and Advantages of Using microRNA (miRNA) as Therapeutic Nucleic Acid
4.4. Principles and Advantages of Using mRNA as Therapeutic Nucleic Acid
4.5. Principles and Advantages of Using Aptamer as Therapeutic Nucleic Acid
4.6. Principles and Advantages of Using Ribozymes as Therapeutic Nucleic Acid
5. Clinical Transformation and Application
Drugs | Target Gene | Delivery System | Disease Type | Status | Clinical Trials Gov Identifier | Reference |
---|---|---|---|---|---|---|
rAAV2-CBSB-hRPE65(cDNA) | RPE65 | Recombinant adeno-associated virus serotype 2 (rAAV2) | Amaurosis of Leber | Phase 1 active, not recruiting | NCT00481546 | [7] |
rAAV2-VMD2 (cDNA) | MERTK | rAAV2 | Retinitis pigmentosa | Phase 1 completed | NCT01482195 | [120] |
RGX-314 (cDNA) | VEGF | rAAV2 | Neovascular AMD degeneration | Phase 1 | NCT03066258 | [121] |
Pegaptanib (aptamer) | VEGF | Carrier-free | Wet AMD degeneration | Phase 3 | NCT01189461 | [119] |
vMCO-I (cDNA) | MCO | rAAV2 | Retinal degeneration | Phase 1/2 | NCT04919473 | [122] |
QR-1123 (ASO) | P23H | Water-based formulation | Retinal dystrophies | Phase 1/2 | NCT04123626 | [123] |
SYL040012 (siRNA) | ADRB2 | Carrier-free | Glaucoma | Phase 1 | NCT00990743 | [124] |
SYL1001 (siRNA) | TRPV1 | Carrier-free | Dry-eye disease | Phase 3 | NCT03108664 | [125] |
AGN211745 (siRNA) | VEGF-1 | Carrier-free | Neovascular AMD | Phase 1/2 | NCT00363714 | [116] |
ISTH0036 (ASO) | TGF-β2 | Water-based formulation | Primary open-angle glaucoma | Phase 1 | NCT02406833 | [117] |
6. Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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Types | Characteristics | Advantages | Disadvantages | Examples | References |
---|---|---|---|---|---|
cDNA | Long nucleotide sequences encoding specific proteins | High stability | Possibly inserted genome | rAAV8-Reep6.1 (rescuing Reep6 mutation via gene replacement therapy) | [24] |
siRNA | Short nucleic acid double strand | Specific knockdown gene expression | Poor stability | AGN211745TM (Treatment of AMD, phase 2 clinical trial) | [25] |
Antisense oligonucleotide | Hairpin structure | Precise regulation of gene expression | Poor stability | ISTH0036 (Treatment of glaucoma, phase 1 clinical trial) | [26] |
Aptamers | Oligonucleotides specifically binding to DNA, RNA, proteins | Simple synthesis, low cost and wide range of action targets | Screening difficulty | ARC1905TM (Phase 1 clinical trial of combination therapy with Lucentis® 0.5 mg/eye for neovascular AMD) | [27] |
Diseases | Disease-Causing Gene | Expression Location | References |
---|---|---|---|
Neovascular glaucoma (NVG) | GNAQ, CFH, Y402H | Retina | [29,30] |
Age-related macular degeneration (AMD) | ARMS2/HTRA1, Y402H, ARMS2, VEGF-R, EST1 | Choriocapillaris | [31,32,33,34] |
High myopia (HM) | ZNF644, P4HA2, SLC39A5, BSG, LRPAP1, LEPREL1, CTSH, OPN1, LW, ARR3 | Retina, retinal pigment epithelium | [35,36,37,38] |
Retinitis pigmentosa (RP) | RHO, PRPF31, USH2A, Peripherin/RDS, NRL, RP1, RGR, ABCA4, RPE65, CNCG | Retina | [39,40,41,42] |
Primary congenital glaucoma (PCG) | CYP1B1, MYOC, LTBP2, FOXC1 | Cornea, ciliary body, iris and retina | [43,44,45,46] |
Congenital aniridia | PAX6 | Lens, iris | [47] |
Xerophthalmia | TRP | Cornea | [48] |
Cataract | CRYAA, COL4A1, BFSP | Lens | [49,50,51] |
Uveitis | Peripherin/RDS, DRB1/DQA1, IL23R/C1orf141 ADO/ZNF365/EGR2 | Iris, lens, choroid | [52] |
Choroidal neovascularization (CNV) | SDF-1, CXCR4, VEGF | Choriocapillaris | [53] |
Diabetic retinopathy (DR) | VEGF, AR, AGE, RAGE, ACE, NOS | Vitreous vessels | [54,55] |
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Ren, W.; Duan, S.; Dai, C.; Xie, C.; Jiang, L.; Shi, Y. Nanotechnology Lighting the Way for Gene Therapy in Ophthalmopathy: From Opportunities toward Applications. Molecules 2023, 28, 3500. https://doi.org/10.3390/molecules28083500
Ren W, Duan S, Dai C, Xie C, Jiang L, Shi Y. Nanotechnology Lighting the Way for Gene Therapy in Ophthalmopathy: From Opportunities toward Applications. Molecules. 2023; 28(8):3500. https://doi.org/10.3390/molecules28083500
Chicago/Turabian StyleRen, Weiming, Suyang Duan, Chao Dai, Chunbao Xie, Lingxi Jiang, and Yi Shi. 2023. "Nanotechnology Lighting the Way for Gene Therapy in Ophthalmopathy: From Opportunities toward Applications" Molecules 28, no. 8: 3500. https://doi.org/10.3390/molecules28083500