Small activating RNA activation of ATOH1 promotes regeneration of human inner ear hair cells

Zhang, Yongli; Kang, Moorim; Wu, Jian-Cheng; Xie, Meng-Yao; Xue, Ruoyan; Tang, Qi; Yang, Hua; Li, Long-Cheng

doi:10.1080/21655979.2022.2045835

Cited by 4 publications

(2 citation statements)

References 31 publications

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“…The expression patterns of the hypermethylated 1 ( HIC1 ) transcriptional repressor and Prox1 genes do not overlap with Atoh1 and related downstream genes, and studies confirm that both have a repressive effect on Atoh1 and are responsible for the decrease in Atoh1 expression in postnatal mice, whereas knockdown of HIC1 or Prox1 reverses the repression of Atoh1 expression and ultimately promotes the differentiation of HCs ( Kirjavainen et al, 2008 ; Abdul-Aziz et al, 2021 ). Meanwhile, an increase in Atoch1 expression was induced by the Atoch1 enhancer or small activating RNA to regulate HC regeneration ( Luo et al, 2022 ; Zhang et al, 2022 ).…”

Section: Gene Therapy Promotes the Regeneration Of Hcsmentioning

confidence: 99%

Gene therapy: an emerging therapy for hair cells regeneration in the cochlea

et al. 2023

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Sensorineural hearing loss is typically caused by damage to the cochlear hair cells (HCs) due to external stimuli or because of one’s genetic factors and the inability to convert sound mechanical energy into nerve impulses. Adult mammalian cochlear HCs cannot regenerate spontaneously; therefore, this type of deafness is usually considered irreversible. Studies on the developmental mechanisms of HC differentiation have revealed that nonsensory cells in the cochlea acquire the ability to differentiate into HCs after the overexpression of specific genes, such as Atoh1, which makes HC regeneration possible. Gene therapy, through in vitro selection and editing of target genes, transforms exogenous gene fragments into target cells and alters the expression of genes in target cells to activate the corresponding differentiation developmental program in target cells. This review summarizes the genes that have been associated with the growth and development of cochlear HCs in recent years and provides an overview of gene therapy approaches in the field of HC regeneration. It concludes with a discussion of the limitations of the current therapeutic approaches to facilitate the early implementation of this therapy in a clinical setting.

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Section: Gene Therapy Promotes the Regeneration Of Hcsmentioning

confidence: 99%

Gene therapy: an emerging therapy for hair cells regeneration in the cochlea

et al. 2023

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“…RNA activation (RNAa) is a gene regulation mechanism by which promoter-targeted small activating RNAs (saRNAs) induce transcriptional gene activation in a sequence specific manner [ 6 , 10 ]. Targeted activation of therapeutic genes by saRNAs has been demonstrated in a variety of disease models including cancer and noncancerous diseases [ 11 , 12 ]. A saRNA drug designed to activate the tumor suppressor gene CEBPA is in phase II trial for the treatment of liver cancer [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

p21CIP/WAF1 saRNA inhibits proliferative vitreoretinopathy in a rabbit model

Zhang

Guo

Kang³

et al. 2023

PLoS ONE

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Purpose Proliferative vitreoretinopathy (PVR) is a disease process resulting from proliferation of retinal pigment epithelial (RPE) cells in the vitreous and periretinal area, leading to periretinal membrane formation and traction and eventually to postoperative failure after vitreo-retinal surgery for primary rhegmatogenous retinal detachment (RRD). The present study was designed to test the therapeutic potential of a p21CIP/WAF1 (p21) inducing saRNA for PVR. Methods A chemically modified p21 saRNA (RAG1-40-53) was tested in cultured human RPE cells for p21 induction and for the inhibition of cell proliferation, migration and cell cycle progression. RAG1-40-53 was further conjugated to a cholesterol moiety and tested for pharmacokinetics and pharmacodynamics in rabbit eyes and for therapeutic effects after intravitreal administration in a rabbit PVR model established by injecting human RPE cells. Results RAG1-40-53 (0.3 mg, 1 mg) significantly induced p21 expression in RPE cells and inhibited cell proliferation, the progression of cell cycle at the G0/G1 phase and TGF-β1 induced migration. After a single intravitreal injection into rabbit eyes, cholesterol-conjugated RAG1-40-53 exhibited sustained concentration in the vitreal humor beyond at least 8 days and prevented the progression of established PVR. Conclusion p21 saRNA could represent a novel therapeutics for PVR by exerting a antiproliferation and antimigration effect on RPE cells.

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Activation of Wnt/β-catenin signaling to increase B lymphoma Moloney murine leukemia virus insertion region 1 by lithium chloride attenuates the toxicity of cisplatin in the HEI-OC1 auditory cells

Lu,

Chen,

et al. 2025

Toxicology Letters

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Small activating RNA activation of ATOH1 promotes regeneration of human inner ear hair cells

Cited by 4 publications

References 31 publications

Gene therapy: an emerging therapy for hair cells regeneration in the cochlea

Gene therapy: an emerging therapy for hair cells regeneration in the cochlea

p21CIP/WAF1 saRNA inhibits proliferative vitreoretinopathy in a rabbit model

Activation of Wnt/β-catenin signaling to increase B lymphoma Moloney murine leukemia virus insertion region 1 by lithium chloride attenuates the toxicity of cisplatin in the HEI-OC1 auditory cells

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