Adeno-associated virus (AAV) based gene therapy for eye diseases

Wang, Shuang; Liu, Peng; Song, Lei; Lu, Linwei; Zhang, Wensong; Wu, Yingliang

doi:10.1007/s10561-011-9243-7

Cited by 3 publications

(2 citation statements)

References 54 publications

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“…This is in accordance to what is described by Haase et al, 10 which has shown these plasmids to originate the strongest luciferase expression in vivo, as the hCMV promoter is less affected by epigenetic silencing events than CMV. 12 Although our in vivo study has shown a low number of transfected cells, upon comparison with other studies, where these systems were combined with chitosan nanoparticles for corneal gene delivery 25 or AAVs used for retinal transduction, 26 the amount of DNA we used was significantly lower than in other studies (100 ng compared with 1.5 mg 25 ). However, our results show that by using only 100 ng of DNA, we could achieve a transfection efficiency of 1.5-2% of the ganglion cells.…”

Section: Discussionmentioning

confidence: 58%

Sustained Gene Expression in the Retina by Improved Episomal Vectors

Oliveira¹,

Machado²,

Haase³

et al. 2014

Tissue Engineering Part A

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Gene and cellular therapies are nowadays part of therapeutic strategies for the treatment of diverse pathologies. The drawbacks associated with gene therapy-low levels of transgene expression, vector loss during mitosis, and gene silencing-need to be addressed. The pEPI-1 and pEPito family of vectors was developed to overcome these limitations. It contains a scaffold/matrix attachment region, which anchors its replication to cell division in eukaryotic cells while in an extrachromosomal state and is less prone to silencing, due to a lower number of CpG motifs. Recent success showed that ocular gene therapy is an important tool for the treatment of several diseases, pending the overcome of the aforementioned limitations. To achieve sustained gene delivery in the retina, we evaluated several vectors based on pEPito and pEPI-1 for their ability to sustain transgene expression in retinal cells. These vectors stably transfected and replicated in retinal pigment epithelial (RPE) cells. Expression levels were promoter dependent with constitutive promoters cytomegalovirus immediate early promoter (CMV) and human CMV enhancer/human elongation factor 1 alpha promoter yielding the highest levels of transgene expression compared with the retina-specific RPE65 promoter. When injected in C57Bl6 mice, transgene expression was sustained for at least 32 days. Furthermore, the retina-specific RPE65 promoter showed higher efficiency in vivo compared to in vitro. In this study, we demonstrate that by combining tissue-specific promoters with a mitotic stable system, less susceptible to epigenetic silencing such as pEPito-based plasmids, we can achieve prolonged gene expression and a sustained therapeutic effect.

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Section: Discussionmentioning

confidence: 58%

Sustained Gene Expression in the Retina by Improved Episomal Vectors

Oliveira¹,

Machado²,

Haase³

et al. 2014

Tissue Engineering Part A

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“…[17,18] The primary method of gene delivery in ocular space for treating various visual disorders employs viral-based gene transduction. [19][20][21][22] However, the viralbased gene delivery may not be ideal for clinical translation of optogenetics therapy for inherited retinal diseases dealing with geographic atrophies (GA), where patches of the retina have photoreceptor degeneration. Besides, the viral-based delivery method has several limitations, especially having no control over the spread of viral transduction in retina (eg, it transduces pan-retina when injected intravitreally).…”

Section: Introductionmentioning

confidence: 99%

Laser‐assisted targeted gene delivery to degenerated retina improves retinal function

Batabyal¹,

Kim²,

Wright³

et al. 2020

Journal of Biophotonics

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Delivery of therapeutic genes into retina is proving to reverse degeneration and restore vision, however, viral vector-based gene delivery is prone to immunorejection, inflammatory/immune-response and nontargeted. Here, we report nonviral gene delivery and expression of opsin encoding genes in mouse retina in-vitro and in-vivo by use of pulsed femtosecond laser microbeam. In-vitro patch-clamp recording of the opsin-sensitized retinal cells and visually evoked in-vivo electrical recording from laser-transfected eye of mouse with degenerated retina showed functional response. The ultrafast laserbased naked gene delivery showed minimal damage and reliable expression of therapeutic opsin in cell membrane of the selected cells and in targeted retinal region. Laser-based "naked DNA gene therapy" in a spatially targeted manner will pave the way for treatment of inherited retinal diseases.

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Biosafety assessment of delivery systems for clinical nucleic acid therapeutics

Zhang

Jiang

et al. 2022

Biosafety and Health

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Adeno-associated virus (AAV) based gene therapy for eye diseases

Cited by 3 publications

References 54 publications

Sustained Gene Expression in the Retina by Improved Episomal Vectors

Sustained Gene Expression in the Retina by Improved Episomal Vectors

Laser‐assisted targeted gene delivery to degenerated retina improves retinal function

Biosafety assessment of delivery systems for clinical nucleic acid therapeutics

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