Toward the Treatment of Inherited Diseases of the Retina Using CRISPR-Based Gene Editing

Hernández-Juárez, Jennifer; Rodríguez-Uribe, Genaro; Borooah, Shyamanga

doi:10.3389/fmed.2021.698521

Cited by 9 publications

(3 citation statements)

References 111 publications

(159 reference statements)

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“…However, evaluation of the efficacy of these factors and tracking the edited cells in the process of treatment is challenging because procurement of retinal biopsies from patients is not possible for functional analysis. Furthermore, a constant monitoring for adverse side effects is crucial [133].…”

Section: Limitations and Challenges In Using Crispr/cas9 Technology I...mentioning

confidence: 99%

Therapeutic applications of CRISPR/Cas9 gene editing technology for the treatment of ocular diseases

et al. 2023

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Ocular diseases are a highly heterogeneous group of phenotypes, caused by a spectrum of genetic variants and environmental factors that exhibit diverse clinical symptoms. As a result of its anatomical location, structure and immune privilege, the eye is an ideal system to assess and validate novel genetic therapies. Advances in genome editing have revolutionized the field of biomedical science, enabling researchers to understand the biology behind disease mechanisms and allow the treatment of several health conditions, including ocular pathologies. The advent of clustered regularly interspaced short palindromic repeats (CRISPR)‐based gene editing facilitates efficient and specific genetic modifications in the nucleic acid sequence, resulting in permanent changes at the genomic level. This approach has advantages over other treatment strategies and is promising for the treatment of various genetic and non‐genetic ocular conditions. This review provides an overview of the CRISPR/CRISPR‐associated protein 9 (Cas9) system and summarizes recent advances in the therapeutic application of CRISPR/Cas9 for the treatment of various ocular pathologies, as well as future challenges.

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Section: Limitations and Challenges In Using Crispr/cas9 Technology I...mentioning

confidence: 99%

Therapeutic applications of CRISPR/Cas9 gene editing technology for the treatment of ocular diseases

et al. 2023

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“…The collaboration of in vitro studies and the in vivo validation of these hypotheses will advance current regenerative therapies to break paradigms on vision restoration. Refer to Table 2 for a detailed summary of the advantages and disadvantages of in vivo therapies to restore vision, as well as the use of in vitro approaches to characterize MG gliosis [79][80][81][82][83].…”

Section: In Vitro Approaches To Examine Gliosis In the Retinamentioning

confidence: 99%

Harnessing the Neuroprotective Behaviors of Müller Glia for Retinal Repair

Peña¹,

Vázquez²

2022

Front. Biosci. (Landmark Ed)

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Progressive and irreversible vision loss in mature and aging adults creates a health and economic burden, worldwide. Despite the advancements of many contemporary therapies to restore vision, few approaches have considered the innate benefits of gliosis, the endogenous processes of retinal repair that precede vision loss. Retinal gliosis is fundamentally driven by Müller glia (MG) and is characterized by three primary cellular mechanisms: hypertrophy, proliferation, and migration. In early stages of gliosis, these processes have neuroprotective potential to halt the progression of disease and encourage synaptic activity among neurons. Later stages, however, can lead to glial scarring, which is a hallmark of disease progression and blindness. As a result, the neuroprotective abilities of MG have remained incompletely explored and poorly integrated into current treatment regimens. Bioengineering studies of the intrinsic behaviors of MG hold promise to exploit glial reparative ability, while repressing neuro-disruptive MG responses. In particular, recent in vitro systems have become primary models to analyze individual gliotic processes and provide a stepping stone for in vivo strategies. This review highlights recent studies of MG gliosis seeking to harness MG neuroprotective ability for regeneration using contemporary biotechnologies. We emphasize the importance of studying gliosis as a reparative mechanism, rather than disregarding it as an unfortunate clinical prognosis in diseased retina.

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“…2). Diseases resulting from LOF mutations can be targeted by conventional gene replacement, nonsense suppression, and exon skipping8 therapies, whereas diseases resulting from GOF mutations need to be targeted by gene editing,9 antisense oligonucleotide,10 or small interfering RNA (siRNA)11 therapies.…”

Section: Introductionmentioning

confidence: 99%

Emerging Gene Manipulation Strategies for the Treatment of Monogenic Eye Disease

Burgess

Hall

Megaw

2022

Asia-Pacific Journal of Ophthalmology

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Genetic eye diseases, representing a wide spectrum of simple and complex conditions, are one of the leading causes of visual loss in children and working adults, and progress in the field has led to changes in disease investigation, diagnosis, and management. The past 15 years have seen the emergence of novel therapies for these previously untreatable conditions to the extent that we now have a licensed therapy for one form of genetic eye disease and many more in clinical trial. This is a systematic review of published and ongoing clinical trials of gene therapies for monogenic eye diseases. Databases of clinical trials and the published literature were searched for interventional studies of gene therapies for eye diseases. Standard methodological procedures were used to assess the relevance of search results. A total of 59 registered clinical trials are referenced, showing the significant level of interest in the potential for translation of these therapies from bench to bedside. The breadth of therapy design is encouraging, providing multiple possible therapeutic mechanisms. Some fundamental questions regarding gene therapy for genetic eye diseases remain, such as optimal dosing, the relative benefits of adeno-associated virus (AAV)–packaging and the potential for a significant inflammatory response to the therapy itself. As a result, despite the promise of the eye as a target, it has proven difficult to deliver clinically effective gene therapies to the eye. Despite setbacks, the licensing of Luxturna (voretigene neparvovec, Novartis) for the treatment of RPE65-mediated Leber congenital amaurosis (LCA) is a major advance in efforts to treat these rare, but devastating, causes of visual loss.

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Toward the Treatment of Inherited Diseases of the Retina Using CRISPR-Based Gene Editing

Cited by 9 publications

References 111 publications

Therapeutic applications of CRISPR/Cas9 gene editing technology for the treatment of ocular diseases

Therapeutic applications of CRISPR/Cas9 gene editing technology for the treatment of ocular diseases

Harnessing the Neuroprotective Behaviors of Müller Glia for Retinal Repair

Emerging Gene Manipulation Strategies for the Treatment of Monogenic Eye Disease

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