ArticleNature communications2019
CRISPR/Cas9 editing of APP C-terminus attenuates β-cleavage and promotes α-cleavage.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
72 citing papers in PubMed, 114 citations in OpenAlex.
- Article
- Neuropsychiatric drug development in China: Current status and emerging trends.Molecular psychiatry · 2026Review
- CRISPR-Cas9 and next-generation gene editing strategies for therapeutic intervention of neurodegenerative pathways in Alzheimer's disease: a state-of-the-art review.Acta neurologica Belgica · 2026Review
- CRISPR-Cas9 Therapeutics in Early Clinical Development: Delivery and Molecular Diagnostics.Cells · 2026Review
- A Translational Roadmap for Neurological Nonsense Mutation Disorders.International journal of molecular sciences · 2026Review
- Generation of hiPSC-Derived Brain Microvascular Endothelial Cells Using Directed Differentiation and Transcriptional Reprogramming.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Unique Expression and Glycosylation of Amyloid Precursor Protein in Alzheimer's Disease.Advances in experimental medicine and biology · 2026Review
- Controlling CRISPR-Cas9 genome editing in human cells using a molecular glue degrader.Molecular therapy. Nucleic acids · 2025Article
- Review
- Beyond Transgenic Mice: Emerging Models and Translational Strategies in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Engineering ARMMs for improved intracellular delivery of CRISPR-Cas9.Extracellular vesicle · 2025Article
- CRISPR/Cas9-Based therapeutics as a promising strategy for management of Alzheimer's disease: progress and prospects.Frontiers in cellular neuroscience · 2025Review
- Stem cell and CRISPR/Cas9 gene editing technology in Alzheimer's disease therapy: from basic research to clinical innovation.Frontiers in genome editing · 2025Review
- Significance of gene therapy in neurodegenerative diseases.Frontiers in neuroscience · 2025Review
- CRISPR-Cas technologies in neurodegenerative disorders: mechanistic insights, therapeutic potential, and translational challenges.Frontiers in neurology · 2025Review
- Generating iAstrocytes From Human Induced Pluripotent Stem Cells by Combining Low-Density Passaging of Neural Progenitor Cells and Transcription Factor NFIA Transdifferentiation.Current protocols · 2024Article
- Application of CRISPR/Cas9 System in the Treatment of Alzheimer's Disease and Neurodegenerative Diseases.Molecular neurobiology · 2024Review
- Gene therapy for CNS disorders: modalities, delivery and translational challenges.Nature reviews. Neuroscience · 2024Review
- Xenografted human iPSC-derived neurons with the familial Alzheimer's disease APPActa neuropathologica · 2024Article
- Osteopontin drives neuroinflammation and cell loss in MAPT-N279K frontotemporal dementia patient neurons.Cell stem cell · 2024Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 5 institutions in 1 country.
Funding
Abstract
CRISPR/Cas9 guided gene-editing is a potential therapeutic tool, however application to neurodegenerative disease models has been limited. Moreover, conventional mutation correction by gene-editing would only be relevant for the small fraction of neurodegenerative cases that are inherited. Here we introduce a CRISPR/Cas9-based strategy in cell and animal models to edit endogenous amyloid precursor protein (APP) at the extreme C-terminus and reciprocally manipulate the amyloid pathway, attenuating APP-β-cleavage and Aβ production, while up-regulating neuroprotective APP-α-cleavage. APP N-terminus and compensatory APP-homologues remain intact, with no apparent effects on neurophysiology in vitro. Robust APP-editing is seen in human iPSC-derived neurons and mouse brains with no detectable off-target effects. Our strategy likely works by limiting APP and BACE-1 approximation, and we also delineate mechanistic events that abrogates APP/BACE-1 convergence in this setting. Our work offers conceptual proof for a selective APP silencing strategy.
Indexed as
Identifiers
What OpenQuestion holds
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.