ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019
Long-Term Effects of In Vivo Genome Editing in the Mouse Retina Using Campylobacter jejuni Cas9 Expressed via Adeno-Associated Virus.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Recombinant Adeno-Associated Viral Vectors (rAAV)-Vector Elements in Ocular Gene Therapy Clinical Trials and Transgene Expression and Bioactivity Assays.International journal of molecular sciences · 2020Pooled it
- Review
- Therapeutic in vivo genome editing: innovations and challenges in rAAV vector-based CRISPR delivery.Gene therapy · 2026Review
- Rationally designedMolecular therapy. Nucleic acids · 2024Article
- CRISPR-mediated ablation of TP53 and EGFR mutations enhances gefitinib sensitivity and anti-tumor efficacy in lung cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Navigating the CRISPR/Cas Landscape for Enhanced Diagnosis and Treatment of Wilson's Disease.Cells · 2024Review
- Multifunctional nano-in-micro delivery systems for targeted therapy in fundus neovascularization diseases.Journal of nanobiotechnology · 2024Review
- Advances in Recombinant Adeno-Associated Virus Vectors for Neurodegenerative Diseases.Biomedicines · 2023Review
- Mini-PE, a prime editor with compact Cas9 and truncated reverse transcriptase.Molecular therapy. Nucleic acids · 2023Article
- Multi-faceted CRISPR/Cas technological innovation aspects in the framework of 3P medicine.The EPMA journal · 2023Review
- Long-Term Evaluation of Retinal Morphology and Function in Rosa26-Cas9 Knock-In Mice.International journal of molecular sciences · 2023Article
- Enhancement of Gene Editing and Base Editing with Therapeutic Ribonucleoproteins through In Vivo Delivery Based on Absorptive Silica Nanoconstruct.Advanced healthcare materials · 2023Article
- Expanded targeting scope of LbCas12a variants allows editing of multiple oncogenic mutations.Molecular therapy. Nucleic acids · 2022Article
- Genome editing-mediated knock-in of therapeutic genes ameliorates the disease phenotype in a model of hemophilia.Molecular therapy. Nucleic acids · 2022Article
- CRISPR-based VEGF suppression using paired guide RNAs for treatment of choroidal neovascularization.Molecular therapy. Nucleic acids · 2022Article
- Engineered Campylobacter jejuni Cas9 variant with enhanced activity and broader targeting range.Communications biology · 2022Article
- Delivery strategies for CRISPR/Cas genome editing tool for retinal dystrophies: challenges and opportunities.Asian journal of pharmaceutical sciences · 2022Review
- Site-directed RNA editing: recent advances and open challenges.RNA biology · 2021Review
- Recent advances in CRISPR technologies for genome editing.Archives of pharmacal research · 2021Review
- MiniCAFE, a CRISPR/Cas9-based compact and potent transcriptional activator, elicits gene expression in vivo.Nucleic acids research · 2021Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genome editing with CRISPR systems provides an unprecedented opportunity to modulate cellular responses in pathological conditions by inactivating undruggable targets, such as transcription factors. Previously, we demonstrated that the smallest Cas9 ortholog characterized to date, from Campylobacter jejuni (CjCas9) targeted to Hif1a and delivered in an adeno-associated virus (AAV) vector, effectively suppressed pathological choroidal neovascularization in the mouse retina. Before implementation of CjCas9 as an in vivo therapeutic modality, it is essential to investigate the long-term effects of target gene disruption via AAV-mediated delivery of CjCas9 in vivo. In this study, histologic and electroretinographic analyses demonstrated that CjCas9 targeted to Hif1a did not induce any definite toxicity in the retina, although the target gene was mutated with a frequency ranging from 45% to 79% in retinal or retinal pigment epithelial cells. Importantly, at 14 months after injection, no indels were detected at potential off-target sites identified using Digenome-seq and Cas-OFFinder, suggesting that long-term expression of CjCas9 does not aggravate off-target effects. Taken together, our results show that intravitreal injection of AAV encoding CjCas9 targeted to Hif1a effectively induced and maintained mutations in retinal tissues for more than 1 year and did not affect retinal histologic integrity or functions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.