CRISPR/Cas9–mediated metabolic pathway reprogramming in a novel humanized rat model ameliorates primary hyperoxaluria type 1

Zheng, Rui; Li, Yueyan; Wang, Liren; Fang, Xiaoliang; Zhang, Junqi; He, Lei; Yang, Lei; Li, Dali; Geng, Hui

doi:10.1016/j.kint.2020.04.049

Cited by 29 publications

(28 citation statements)

References 36 publications

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“…We have recently reported a PH1 rat model that exhibited high urinary oxalate levels at an early age, highly mimicking PH1 in humans 18 . In the present study, using the same rat model, we observed a sustained reduction of LDH after a single administration of AAV‐delivered CRISPR/Cas9 system that targets rat Ldha .…”

Section: Discussionsupporting

confidence: 73%

“…We have recently reported a PH1 rat model that exhibited high urinary oxalate levels at an early age, highly mimicking PH1 in humans. 18 In the present study, using the same rat model, we observed a sustained reduction of LDH after a single administration of AAV-delivered CRISPR/Cas9 system that targets rat Ldha. Moreover, we achieved a long-term reduction in endogenous oxalate synthesis and a decrease in kidney CaOx precipitation in the treated PH1 rats, demonstrating the therapeutic potentials of this approach.…”

Section: Discussionsupporting

confidence: 65%

“…In our PH1 rat model, at least a 30-45% indel rate of Hao1 was required to achieve similar efficacy. 18 The efficiency of genome editing in liver might be underestimated, as studies have shown that the AAV cannot transfect nonparenchymal cells, which accounts for nearly half of the liver cells (we used total liver tissue for indel detection). 30,31 Accordingly, our data showed a more considerable reduction in the LDH protein level compared to the indel rate.…”

Section: Discussionmentioning

confidence: 99%

“…Western blot analyses were performed on rat liver lysates, as described previously. 18 LDH protein was probed with an anti-LDH antibody (ab52488, Abcam, UK) diluted at 1:2000. Mouse anti-β-actin antibody diluted at 1:2000 (A5441, Sigma, Germany) was used to detect β-actin.…”

Section: Western Blot Analysismentioning

confidence: 99%

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Knockdown of lactate dehydrogenase by adeno‐associated virus‐delivered CRISPR/Cas9 system alleviates primary hyperoxaluria type 1

Zheng

Fang

Chen

et al. 2020

Clinical & Translational Med

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Section: Discussionsupporting

confidence: 73%

Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Western Blot Analysismentioning

confidence: 99%

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Knockdown of lactate dehydrogenase by adeno‐associated virus‐delivered CRISPR/Cas9 system alleviates primary hyperoxaluria type 1

Zheng

Fang

Chen

et al. 2020

Clinical & Translational Med

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“…46 Recently, Estève et al 47 Another team also showed that it was possible to inhibit the HAO1 gene (encoding GO) using CRISPR/Cas9, leading to the reduction of urine oxalate levels to normal levels and prevent nephrocalcinosis formation without toxic effects in a murine PH1 model. 49,50 Delivery of normal AGXT gene through viral vectors are also in preclinical development. 14 Adeno-associated virus (AAV) 5 and AAV8 vectors have shown their efficacy to reduced Uox in PH1 mice models.…”

Section: Gene Therapymentioning

confidence: 99%

Transplantation for Primary Hyperoxaluria Type 1: Designing New Strategies in the Era of Promising Therapeutic Perspectives

Devresse

Cochat

Godefroid

et al. 2020

Kidney International Reports

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Gene editing in liver diseases

Torella,

Santana‐Gonzalez,

Zabaleta

et al. 2024

FEBS Letters

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The deliberate and precise modification of the host genome using engineered nucleases represents a groundbreaking advancement in modern medicine. Several clinical trials employing these approaches to address metabolic liver disorders have been initiated, with recent remarkable outcomes observed in patients with transthyretin amyloidosis, highlighting the potential of these therapies. Recent technological improvements, particularly CRISPR Cas9‐based technology, have revolutionized gene editing, enabling in vivo modification of the cellular genome for therapeutic purposes. These modifications include gene supplementation, correction, or silencing, offering a wide range of therapeutic possibilities. Moving forward, we anticipate witnessing the unfolding therapeutic potential of these strategies in the coming years. The aim of our review is to summarize preclinical data on gene editing in animal models of inherited liver diseases and the clinical data obtained thus far, emphasizing both therapeutic efficacy and potential limitations of these medical interventions.

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CRISPR/Cas9–mediated metabolic pathway reprogramming in a novel humanized rat model ameliorates primary hyperoxaluria type 1

Cited by 29 publications

References 36 publications

Knockdown of lactate dehydrogenase by adeno‐associated virus‐delivered CRISPR/Cas9 system alleviates primary hyperoxaluria type 1

Knockdown of lactate dehydrogenase by adeno‐associated virus‐delivered CRISPR/Cas9 system alleviates primary hyperoxaluria type 1

Transplantation for Primary Hyperoxaluria Type 1: Designing New Strategies in the Era of Promising Therapeutic Perspectives

Gene editing in liver diseases

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