CRISPR-Based Genome Editing as a New Therapeutic Tool in Retinal Diseases

Rasoulinejad, Seyed Ahmad; Maroufi, Faezeh

doi:10.1007/s12033-021-00345-4

Cited by 11 publications

(7 citation statements)

References 114 publications

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“…Depending upon the success of the clinical phase II/III trials of Sepofarsen, it can be the first AON therapeutics that is approved by the FDA. CRISPR-Cas9 system with dual AAV genome integration has been suggested as another approach for the efficient treatment of LCA10 ( Ruan et al, 2017 ; Rasoulinejad and Maroufi, 2021 ). Despite its successful implication for the treatment of IVS26 splice mutation in LCA10, the long-term effects regarding bacterial Cas9 protein as well as the off-target effect are still a concern ( Ruan et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Gene regulatory and gene editing tools and their applications for retinal diseases and neuroprotection: From proof-of-concept to clinical trial

Altay

Özdemir²,

Afghah³

et al. 2022

Front. Neurosci.

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Gene editing and gene regulatory fields are continuously developing new and safer tools that move beyond the initial CRISPR/Cas9 technology. As more advanced applications are emerging, it becomes crucial to understand and establish more complex gene regulatory and editing tools for efficient gene therapy applications. Ophthalmology is one of the leading fields in gene therapy applications with more than 90 clinical trials and numerous proof-of-concept studies. The majority of clinical trials are gene replacement therapies that are ideal for monogenic diseases. Despite Luxturna’s clinical success, there are still several limitations to gene replacement therapies including the size of the target gene, the choice of the promoter as well as the pathogenic alleles. Therefore, further attempts to employ novel gene regulatory and gene editing applications are crucial to targeting retinal diseases that have not been possible with the existing approaches. CRISPR-Cas9 technology opened up the door for corrective gene therapies with its gene editing properties. Advancements in CRISPR-Cas9-associated tools including base modifiers and prime editing already improved the efficiency and safety profile of base editing approaches. While base editing is a highly promising effort, gene regulatory approaches that do not interfere with genomic changes are also becoming available as safer alternatives. Antisense oligonucleotides are one of the most commonly used approaches for correcting splicing defects or eliminating mutant mRNA. More complex gene regulatory methodologies like artificial transcription factors are also another developing field that allows targeting haploinsufficiency conditions, functionally equivalent genes, and multiplex gene regulation. In this review, we summarized the novel gene editing and gene regulatory technologies and highlighted recent translational progress, potential applications, and limitations with a focus on retinal diseases.

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Section: Discussionmentioning

confidence: 99%

Gene regulatory and gene editing tools and their applications for retinal diseases and neuroprotection: From proof-of-concept to clinical trial

Altay

Özdemir²,

Afghah³

et al. 2022

Front. Neurosci.

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“…Genetic counseling can not only assist the diagnosis of the proband, but also identify the type of NCMD and the underlying genetic cause of the disease through whole-genome sequencing, thus providing the possibility for further treatment [ 2 , 9 ]. For example, Clustered regularly interspaced short palindromic repeats/crispr-associated protein-9 nuclease (CRISPR/Cas9) system as a frontier tool of gene-editing tools has been studied in the treatment of retinal degenerative diseases [ 15 ]. Research on techniques such as reducing the overexpression of PRDM13 by CRISPR/Cas9 or autologous transplantation combining CRISPR/Cas9 with human-induced pluripotent stem cells may provide effective treatments for NCMD [ 15 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…For example, Clustered regularly interspaced short palindromic repeats/crispr-associated protein-9 nuclease (CRISPR/Cas9) system as a frontier tool of gene-editing tools has been studied in the treatment of retinal degenerative diseases [ 15 ]. Research on techniques such as reducing the overexpression of PRDM13 by CRISPR/Cas9 or autologous transplantation combining CRISPR/Cas9 with human-induced pluripotent stem cells may provide effective treatments for NCMD [ 15 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

The possible pathogenesis of macular caldera in patients with North Carolina macular dystrophy

Zhu

et al. 2022

BMC Ophthalmol

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Background This study provides a detailed description of a Chinese family with North Carolina macular dystrophy (NCMD) and explores its possible pathogenesis. Methods Five individuals from a three-generation family underwent general ophthalmic examination, multi-imaging examinations and visual electrophysiology examinations when possible. Genetic characterization was carried out by target region sequencing and high-throughput sequencing in affected patients. Results Despite severe fundus changes, patients had relatively good visual acuity. Genetic analysis showed that affected patients had PRDM13 gene duplication and heterozygous mutations of the ABCA4 gene. Optical coherence tomography (OCT) showed an abnormal retinal pigment epithelium (RPE) layer in patients with grade 2 lesions, while the neurosensory retina was relatively normal. In grade 3 patients, RPE and choroid atrophy were greater than that of the neurosensory retina, showing concentric atrophy. Conclusions RPE and choroidal atrophy were found to play an important role in the development of macular caldera.

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“…The recently emerging CRISPR/CAS9 technique is a solution to this concern. CRISPR/CAS9-mediated gene editing can correct the mutation and restore the normal function of the targeted gene ( Rasoulinejad and Maroufi, 2021 ). A report showed that this technique was capable of correcting ~45% of the mutant allele at the DNA level in a P23H mouse model, significantly delaying the progression of photoreceptor degeneration in the treated area ( Li et al, 2018 ).…”

Section: Strategies For Therapy Of Rhodopsin-related Retinal Disordersmentioning

confidence: 99%

Rhodopsin-associated retinal dystrophy: Disease mechanisms and therapeutic strategies

et al. 2023

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Rhodopsin is a light-sensitive G protein-coupled receptor that initiates the phototransduction cascade in rod photoreceptors. Mutations in the rhodopsin-encoding gene RHO are the leading cause of autosomal dominant retinitis pigmentosa (ADRP). To date, more than 200 mutations have been identified in RHO. The high allelic heterogeneity of RHO mutations suggests complicated pathogenic mechanisms. Here, we discuss representative RHO mutations as examples to briefly summarize the mechanisms underlying rhodopsin-related retinal dystrophy, which include but are not limited to endoplasmic reticulum stress and calcium ion dysregulation resulting from protein misfolding, mistrafficking, and malfunction. Based on recent advances in our understanding of disease mechanisms, various treatment methods, including adaptation, whole-eye electrical stimulation, and small molecular compounds, have been developed. Additionally, innovative therapeutic treatment strategies, such as antisense oligonucleotide therapy, gene therapy, optogenetic therapy, and stem cell therapy, have achieved promising outcomes in preclinical disease models of rhodopsin mutations. Successful translation of these treatment strategies may effectively ameliorate, prevent or rescue vision loss related to rhodopsin mutations.

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CRISPR-Based Genome Editing as a New Therapeutic Tool in Retinal Diseases

Cited by 11 publications

References 114 publications

Gene regulatory and gene editing tools and their applications for retinal diseases and neuroprotection: From proof-of-concept to clinical trial

Gene regulatory and gene editing tools and their applications for retinal diseases and neuroprotection: From proof-of-concept to clinical trial

The possible pathogenesis of macular caldera in patients with North Carolina macular dystrophy

Rhodopsin-associated retinal dystrophy: Disease mechanisms and therapeutic strategies

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