Lentiviral Vectors for Ocular Gene Therapy

Arsenijévic, Yvan; Berger, Adeline; Udry, Florian; Kostic, Corinne

doi:10.3390/pharmaceutics14081605

Cited by 23 publications

(16 citation statements)

References 203 publications

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“…The modifications of viral serotypes or capsid can alter the cellular tropism of the viral vector 73 , 74 , 79 , 80 . In addition, the route of vector delivery, the intraocular environment and proximity of the target tissue to the delivery site help determine the efficiency and selectivity of the transduction 80 , 81 . Based on the anatomy, the IC route provides the most efficient TM transduction in several studies using AAV or LV vectors 54 , 82 .…”

Section: Discussionmentioning

confidence: 99%

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Lentiviral mediated delivery of CRISPR/Cas9 reduces intraocular pressure in a mouse model of myocilin glaucoma

Patil,

Kaipa,

Ranshing

et al. 2024

Sci Rep

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Mutations in myocilin (MYOC) are the leading known genetic cause of primary open-angle glaucoma, responsible for about 4% of all cases. Mutations in MYOC cause a gain-of-function phenotype in which mutant myocilin accumulates in the endoplasmic reticulum (ER) leading to ER stress and trabecular meshwork (TM) cell death. Therefore, knocking out myocilin at the genome level is an ideal strategy to permanently cure the disease. We have previously utilized CRISPR/Cas9 genome editing successfully to target MYOC using adenovirus 5 (Ad5). However, Ad5 is not a suitable vector for clinical use. Here, we sought to determine the efficacy of adeno-associated viruses (AAVs) and lentiviruses (LVs) to target the TM. First, we examined the TM tropism of single-stranded (ss) and self-complimentary (sc) AAV serotypes as well as LV expressing GFP via intravitreal (IVT) and intracameral (IC) injections. We observed that LV_GFP expression was more specific to the TM injected via the IVT route. IC injections of Trp-mutant scAAV2 showed a prominent expression of GFP in the TM. However, robust GFP expression was also observed in the ciliary body and retina. We next constructed lentiviral particles expressing Cas9 and guide RNA (gRNA) targeting MYOC (crMYOC) and transduction of TM cells stably expressing mutant myocilin with LV_crMYOC significantly reduced myocilin accumulation and its associated chronic ER stress. A single IVT injection of LV_crMYOC in Tg-MYOCY437H mice decreased myocilin accumulation in TM and reduced elevated IOP significantly. Together, our data indicates, LV_crMYOC targets MYOC gene editing in TM and rescues a mouse model of myocilin-associated glaucoma.

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Section: Discussionmentioning

confidence: 99%

“…Both FIV and HIV based LV are used in ocular research 82 . LV vector efficiency is currently being investigated in two macular degeneration clinical trials 78 , 81 . Our HIV based VSV-G pseudotyped vector proved to be selective towards the mouse TM via the IVT route.…”

Section: Discussionmentioning

confidence: 99%

Lentiviral mediated delivery of CRISPR/Cas9 reduces intraocular pressure in a mouse model of myocilin glaucoma

Patil,

Kaipa,

Ranshing

et al. 2024

Sci Rep

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“…Lentiviral vectors also offer larger cargo capacity and are being developed for treatment of retinal disease [122] but currently show reduced transduction profiles compared to AAV vectors with transduction typically localized and limited to the RPE [123]. Lentiviral vectors may therefore be considered for RPE targeting and indeed have been used to deliver full length ABE constructs in rd12 mice, achieving up to 29% correction of the mutation in RPE cells with minimal undesired indels and off-target.…”

Section: Single Pe Construct Deliverymentioning

confidence: 99%

Future Perspectives of Prime Editing for the Treatment of Inherited Retinal Diseases

Hansen

McClements

Corydon

et al. 2023

Cells

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Inherited retinal diseases (IRD) are a clinically and genetically heterogenous group of diseases and a leading cause of blindness in the working-age population. Even though gene augmentation therapies have shown promising results, they are only feasible to treat a small number of autosomal recessive IRDs, because the size of the gene is limited by the vector used. DNA editing however could potentially correct errors regardless of the overall size of the gene and might also be used to correct dominant mutations. Prime editing is a novel CRISPR/Cas9 based gene editing tool that enables precise correction of point mutations, insertions, and deletions without causing double strand DNA breaks. Due to its versatility and precision this technology may be a potential treatment option for virtually all genetic causes of IRD. Since its initial description, the prime editing technology has been further improved, resulting in higher efficacy and a larger target scope. Additionally, progress has been achieved concerning the size-related delivery issue of the prime editor components. This review aims to give an overview of these recent advancements and discusses prime editing as a potential treatment for IRDs.

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“…Inhibiting T mobilephone activation by way of lentiviral gene remedy used to be additionally used to suppress graft rejection. Lentivirus mediated overexpression of programmed phone deathligand 1 (PD-L1) in organ-cultured allogeneic rat corneas reduced CD3+CD8+CD161− and CD3+CD8+CD161+ T cells upon transplantation of modified corneas and decreased inflammatory cytokines IFN-γ and IL-6 ensuing in notably higher graft survival [201].…”

Section: Immunomodulatory Factorsmentioning

confidence: 99%

“…Angiogenic privilege, the stability between a low stage of angiogenic and an excessive degree of antiangiogenic factors, has been the key to preserving corneal avascularity [76]. Significant growth has been made in the appreciation of the mechanisms worried in angiogenic privilege, which has led to gene remedy methods the use of transgenic expression of antiangiogenic elements or inactivation of proangiogenic elements by gene silencing [207]. The angiogenic VEGF pathway has been focused via gene switch of VEGF receptors, Flt-1 and Flk-1.…”

Section: Corneal Neovascularizationmentioning

confidence: 99%

Ocular Gene Therapy: Literature Review

Naser,

M. Nasr,

Shehata

2023

IJPSAT

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This literature offers complete information about the advances in gene treatment in the of the eye, inclusive of cornea, conjunctiva, lacrimal gland, and trabecular meshwork. We talked about gene transport systems, collectively with viral and non-viral vectors as exact as gene modifying techniques, generally CRISPR-Cas9, and epigenetic treatments, consisting of antisense and siRNA therapeutics. We moreover furnish a specific assessment of gene treatment has been examined with corresponding outcomes. Disease stipulations embody corneal and conjunctival fibrosis and scarring, corneal epithelial wound healing, corneal graft survival, corneal neovascularization, genetic corneal dystrophies, herpetic keratitis, glaucoma, dry eye disease, and specific ocular surface diseases. Although most of the analyzed consequences on the use and validity of gene treatment at the ocular surface have been offered in vitro or the utilization of animal models, we moreover talked about the on hand human studies. Gene treatment methods are nowadays viewed very promising as rising future remedies of a variety of diseases, and this area is unexpectedly expanding.

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Lentiviral Vectors for Ocular Gene Therapy

Cited by 23 publications

References 203 publications

Lentiviral mediated delivery of CRISPR/Cas9 reduces intraocular pressure in a mouse model of myocilin glaucoma

Lentiviral mediated delivery of CRISPR/Cas9 reduces intraocular pressure in a mouse model of myocilin glaucoma

Future Perspectives of Prime Editing for the Treatment of Inherited Retinal Diseases

Ocular Gene Therapy: Literature Review

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