ArticleJournal of molecular neuroscience : MN2018
Activation of the Anti-Aging and Cognition-Enhancing Gene Klotho by CRISPR-dCas9 Transcriptional Effector Complex.
Article in Journal of molecular neuroscience : MN, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- Epigenetic Aging in Brain Tissue of the Self-Fertilizing Vertebrate,Ecology and evolution · 2026Article
- Dystrophin Restorative and Compensatory Gene Addition Therapies for Duchenne Muscular Dystrophy: Could CRISPRa Provide a Realistic Alternative?Muscles (Basel, Switzerland) · 2025Review
- Advancement of animal and poultry nutrition: Harnessing the power of CRISPR-Cas genome editing technology.Journal of advanced veterinary and animal research · 2024Article
- Novel approaches to increase synaptic resilience as potential treatments for Alzheimer's disease.Seminars in cell & developmental biology · 2023Review
- Design, Construction, and Validation of Targeted Gene Activation with TREE System in Human Cells.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Advances in CRISPR therapeutics.Nature reviews. Nephrology · 2023Review
- Three Tiers to biological escape velocity: The quest to outwit aging.Aging medicine (Milton (N.S.W)) · 2022Review
- Myelin repair in Alzheimer's disease: a review of biological pathways and potential therapeutics.Translational neurodegeneration · 2022Review
- PAM-flexible dual base editor-mediated random mutagenesis and self-activation strategies to improve CRISPRa potency.Molecular therapy. Methods & clinical development · 2022Article
- Review
- Klotho, PTSD, and advanced epigenetic age in cortical tissue.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Klotho as Potential Autophagy Regulator and Therapeutic Target.Frontiers in pharmacology · 2021Review
- Design and methodology of the Aging Nephropathy Study (AGNES): a prospective cohort study of elderly patients with chronic kidney disease.BMC nephrology · 2020Article
- Modulating gene regulation to treat genetic disorders.Nature reviews. Drug discovery · 2020Review
- PTSD and the klotho longevity gene: Evaluation of longitudinal effects on inflammation via DNA methylation.Psychoneuroendocrinology · 2020Article
- A method to specifically activate the Klotho promoter by using zinc finger proteins constructed from modular building blocks and from naturally engineered Egr1 transcription factor backbone.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Cerebrovascular Disease and Cognition in Chronic Kidney Disease Patients.Frontiers in cardiovascular medicine · 2020Review
- Klotho Pathways, Myelination Disorders, Neurodegenerative Diseases, and Epigenetic Drugs.BioResearch open access · 2020Review
- Dead Cas Systems: Types, Principles, and Applications.International journal of molecular sciences · 2019Review
- Telomere Length Is Associated with Disability Progression in Multiple Sclerosis.Annals of neurology · 2019Observational
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Multiple lines of evidence show that the anti-aging and cognition-enhancing protein Klotho fosters neuronal survival, increases the anti-oxidative stress defense, and promotes remyelination of demyelinated axons. Thus, upregulation of the Klotho gene can potentially alleviate the symptoms and/or prevent the progression of age-associated neurodegenerative diseases such as Alzheimer's disease and demyelinating diseases such as multiple sclerosis. Here we used a CRISPR-dCas9 complex to investigate single-guide RNA (sgRNA) targeting the Klotho promoter region for efficient transcriptional activation of the Klotho gene. We tested the sgRNAs within the - 1 to - 300 bp of the Klotho promoter region and identified two sgRNAs that can effectively enhance Klotho gene transcription. We examined the transcriptional activation of the Klotho gene using three different systems: a Firefly luciferase (FLuc) and NanoLuc luciferase (NLuc) coincidence reporter system, a NLuc knock-in in Klotho 3'-UTR using CRISPR genomic editing, and two human cell lines: neuronal SY5Y cells and kidney HK-2 cells that express Klotho endogenously. The two sgRNAs enhanced Klotho expression at both the gene and protein levels. Our results show the feasibility of gene therapy for targeting Klotho using CRISPR technology. Enhancing Klotho levels has a therapeutic potential for increasing cognition and treating age-associated neurodegenerative, demyelinating and other diseases, such as chronic kidney disease and cancer.
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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.