Generation of a gene-corrected isogenic control cell line from an Alzheimer's disease patient iPSC line carrying a A79V mutation in PSEN1

Pires, Carlota; Schmid, Benjamin; Petræus, Carina; Poon, Anna; Nimsanor, Natakarn; Nielsen, Troels Tolstrup; Waldemar, Gunhild; Hjermind, Lena E.; Nielsen, Jørgen E.; Hyttel, Poul; Freude, Kristine

doi:10.1016/j.scr.2016.08.002

Cited by 46 publications

(36 citation statements)

References 3 publications

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“…Ortiz-Virumbrales et al used CRISPR-Cas9 in iPSC neurons derived from a patient carrying the PSEN2 N141I mutation to correct the autosomal dominant mutation, which led to the normalization of the Aβ42/40 ratio (50). The generation of gene-corrected isogenic control iPSC lines from patients has also been performed in patient lines bearing the PSEN1 mutations A79V and L150P and constitutes a useful in vitro disease model to investigate both the mechanisms underlying familial AD and the consequence of Aβ pathology (54,56). In the APP gene, the Swedish mutation is a well characterized, amyloidogenic double mutation that occurs adjacent to the BACE1 cleavage site in APP and causes a two amino acid substitution where lysine and methionine become asparagine and leucine.…”

Section: Attacking the Disease At Its Source: Targeting The Genetic Mmentioning

confidence: 99%

Applying gene‐editing technology to elucidate the functional consequence of genetic and epigenetic variation in Alzheimer’s disease

2020

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Recent studies have highlighted a potential role of genetic and epigenetic variation in the development of Alzheimer’s disease. Application of the CRISPR‐Cas genome‐editing platform has enabled investigation of the functional impact that Alzheimer’s disease‐associated gene mutations have on gene expression. Moreover, recent advances in the technology have led to the generation of CRISPR‐Cas–based tools that allow for high‐throughput interrogation of different risk variants to elucidate the interplay between genomic regulatory features, epigenetic modifications, and chromatin structure. In this review, we examine the various iterations of the CRISPR‐Cas system and their potential application for exploring the complex interactions and disruptions in gene regulatory circuits that contribute to Alzheimer’s disease.

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Section: Attacking the Disease At Its Source: Targeting The Genetic Mmentioning

confidence: 99%

Applying gene‐editing technology to elucidate the functional consequence of genetic and epigenetic variation in Alzheimer’s disease

2020

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“…Genome editing technology could be used also for mutations' correction, generating an isogenic control. For example, Pires and colleagues reported that A79V-iPSC line in combination of A79V-GC-iPSC line could be used to study pathological cellular phenotypes related to A79V mutation in PSEN [32]. Interestingly, the role of iPSCs in AD research was supported also by analyzing neurons derived from iPSCs of patients with Down syndrome that usually have a high risk of developing AD early.…”

Section: Ipscs In Alzheimer's Diseasementioning

confidence: 99%

From Neuronal Differentiation of iPSCs to 3D Neural Organoids: Modeling of Neurodegenerative Diseases

Bordoni¹,

Fantini²,

Pansarasa³

et al. 2019

Recent Advances in Neurodegeneration

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In the last decade, the finding that somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) leads to a great improvement of research involving the use of differentiated stem cells as model of diseases. In the field of neurodegeneration, iPSC technology allowed to culture in vitro all the types of patient-specific neurons, not only helping the discovery of diseases' etiopathology but also testing new drugs with a personalized medicine approach. Moreover, iPSCs can be combined with the 3D bioprinting technology, allowing physiological cell-to-cell interactions, given by a combination of several biomaterials, scaffolds, and cells. This technology combines bioplotter and biomaterials which can encapsulate several types of cells, e.g., iPSCs or differentiated neurons, to develop an innovative cellular model. iPSCs and 3D cell cultures' technologies represent the first step to obtain a more reliable model, like an organoid to facilitate neurodegenerative diseases' investigation.

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“…This is af irmed by fresh studies that have scrutinized the capacity of correcting similar kinds of changes using this gene editing system. Previous studies have also employed CRISPR/Cas9 to set right genetic AD mutations in the PSEN gene in patient-derived iPSCs [22,23]. Also a 60% reduction in exudation of beta-amyloid by CRISPR/Cas9 treatment is established by a novel study on Swedish APP mutation in patient-derived ibroblasts [24].…”

Section: Crispr/cas9 In Treating Alzheimer's Diseasementioning

confidence: 99%

Vigour of CRISPR/Cas9 Gene Editing in Alzheimer’s Disease

Jes¹

2018

J Neurosci Neurol Disord

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Advancing and lethal neurodegenerative malady that chie ly affects older adults and is also the habitual root of dementia [1]. In clinical situation, AD is exhibited with guilefuly progressive memory loss to which other circles of cognition are eventually lawed. Language hindrances and missing of executive skills are the symptoms that typi ies the term dementia. In kernel, AD impedes with remembrance, thoughts, and behavior rigorous enough to affect a person's work, hobbies, and social life. AD is remorselessly progressive and deadly within 5 to 10 years [2]. An extracellular imbecile plaque constitutes of beta-amyloid and an intracellular lesion of shortened and hyper-phosphorylated TAU leading to neuro ibrillary tangles (NFTs) is the foremost archetypal neuro pathological imprints of AD. The missing of synapses is straightly linked to the degree of dementia [3-5]. Early aggregation of beta-amyloid on PET scans allude to, feasibly, a vast salutary window to step in the clew instigating species, proceeding to all downstream events winding up in synapse loss, neurodegeneration and ultimately dementia is the beta-amyloid in the form of toxic oligomers [6-9]. The stimulus for the budding and analyzing of the irst known disease-correcting therapeutics that conjointly had a deed of either prohibiting beta-amyloid from shaping or led to ampli ied clearance out of the brain is provided by the approach of the betaamyloid hypothesis [10]. Regardless of the numerous number of clinical studies on AD, many are in vain. There are many ostensible reasons for these clinical trial failures. Due to the numerous failures recorded for the current disease-tweaking approaches, now may be time to solemnly convergence on other inherent treatment criterion including gene editing systems. Zinc inger nucleases (ZFNs), Transcription activatorlike Effectors Nucleases (TALENs) and the CRISPR-associated nuclease 9 (CRISPR/ Cas9) are the three gene editing tools procurable for AD. However, this review will focus on the bene it and avail of the CRISPR/Cas9 because it is quicker, affordable, more veracious and effectual than other present genome editing methods.

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Generation of a gene-corrected isogenic control cell line from an Alzheimer's disease patient iPSC line carrying a A79V mutation in PSEN1

Cited by 46 publications

References 3 publications

Applying gene‐editing technology to elucidate the functional consequence of genetic and epigenetic variation in Alzheimer’s disease

Applying gene‐editing technology to elucidate the functional consequence of genetic and epigenetic variation in Alzheimer’s disease

From Neuronal Differentiation of iPSCs to 3D Neural Organoids: Modeling of Neurodegenerative Diseases

Vigour of CRISPR/Cas9 Gene Editing in Alzheimer’s Disease

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