Genetic Modulation of RNA Splicing with a CRISPR-Guided Cytidine Deaminase

Yuan, Jing; Ma, Yunqing; Huang, Tao; Chen, Yanhao; Peng, Yuanzheng; Li, Bing; Li, Jia; Zhang, Yuchen; Song, Bing; Sun, Xiaofang; Ding, Qiurong; Song, Yan; Chang, Xing

doi:10.1016/j.molcel.2018.09.002

Cited by 131 publications

(105 citation statements)

References 49 publications

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“…34,35 Correction of mutations in DMD cells could be achieved by CT followed by differentiation to muscle cells and their injection in the muscles, an option that has been used by several researchers in muscle pathology. 27,33,[36][37][38] The only needed additional step to the protocol used herein is the inactivation, before retro-MMCT fusion, of the HPRT gene on the endogenous X chromosome by CRISPR technology, allowing the use of HAT selection after retro-MMCT. We have recently shown the feasibility of this step by correcting the genetic defect in iPSCs from a mouse model of the X-linked CGD.…”

Section: Discussionmentioning

confidence: 99%

Chromosome Transplantation: A Possible Approach to Treat Human X-linked Disorders

Paulis

Susani

Castelli

et al. 2020

Molecular Therapy - Methods & Clinical Development

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Many human genetic diseases are associated with gross mutations such as aneuploidies, deletions, duplications, or inversions. For these "structural" disorders, conventional gene therapy, based on viral vectors and/or on programmable nuclease-mediated homologous recombination, is still unsatisfactory. To correct such disorders, chromosome transplantation (CT), defined as the perfect substitution of an endogenous defective chromosome with an exogenous normal one, could be applied. CT re-establishes a normal diploid cell, leaving no marker of the procedure, as we have recently shown in mouse pluripotent stem cells. To prove the feasibility of the CT approach in human cells, we used human induced pluripotent stem cells (hiPSCs) reprogrammed from Lesch-Nyhan (LN) disease patients, taking advantage of their mutation in the X-linked HPRT gene, making the LN cells selectable and distinguishable from the resistant corrected normal cells. In this study, we demonstrate, for the first time, that CT is feasible in hiPSCs: the normal exogenous X chromosome was first transferred using an improved chromosome transfer system, and the extra sex chromosome was spontaneously lost. These CT cells were functionally corrected and maintained their pluripotency and differentiation capability. By inactivation of the autologous HPRT gene, CT paves the way to the correction of hiPSCs from several X-linked disorders.

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Section: Discussionmentioning

confidence: 99%

Chromosome Transplantation: A Possible Approach to Treat Human X-linked Disorders

Paulis

Susani

Castelli

et al. 2020

Molecular Therapy - Methods & Clinical Development

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“…Yuan et al (2018) used a catalytically deficient version of Cas9 (dCas9) fused to a cytidine deaminase to specifically edit single DNA bases [97]. Applying this to eliminate the exon 50 donor splice site in exon 51-deleted patient hiPSCs, they achieved exon 50 skipping and dystrophin production in iCMs.…”

Section: Studies Using Human Ipsc Modelsmentioning

confidence: 99%

Genome Editing for the Understanding and Treatment of Inherited Cardiomyopathies

Nguyen

Lim

Yokota

2020

IJMS

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Cardiomyopathies are diseases of heart muscle, a significant percentage of which are genetic in origin. Cardiomyopathies can be classified as dilated, hypertrophic, restrictive, arrhythmogenic right ventricular or left ventricular non-compaction, although mixed morphologies are possible. A subset of neuromuscular disorders, notably Duchenne and Becker muscular dystrophies, are also characterized by cardiomyopathy aside from skeletal myopathy. The global burden of cardiomyopathies is certainly high, necessitating further research and novel therapies. Genome editing tools, which include zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR) systems have emerged as increasingly important technologies in studying this group of cardiovascular disorders. In this review, we discuss the applications of genome editing in the understanding and treatment of cardiomyopathy. We also describe recent advances in genome editing that may help improve these applications, and some future prospects for genome editing in cardiomyopathy treatment.

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“…The single base‐editing technology has been used not only in mice to model human diseases but also directly in human cells (G. Li et al, ; Liang, Ding et al, ; Yuan et al, ; Zeng et al, ; Zhou et al, ). The CBE3 and SaKKH‐BE3 (PAM is NNNRRT) systems have been used to mutate one or three genes simultaneously in human trigeminal zygotes with very high efficiency, indicating that CBE3 induces near perfect gene editing in the target site with extremely low off‐target mutagenesis and indel mutations in human cells (G. Li et al, ; Zhou et al, ).…”

Section: Applications Of Crispr‐mediated Base Editingmentioning

confidence: 99%

“…RNA splicing is a critical mechanism by which to modify transcriptome, and its dysregulation is associated with many human diseases. Intriguingly, a report has shown that TAM can be used to modulate RNA splicing by editing splice sites (Yuan et al, ). Thus, the CRISPR‐guided cytidine deaminase provides a versatile genetic platform to modulate RNA splicing and correct mutations associated with aberrant splicing in human diseases (Yuan et al, ).…”

Section: Applications Of Crispr‐mediated Base Editingmentioning

confidence: 99%

Single‐nucleotide editing: From principle, optimization to application

2019

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Cytosine base editors (CBEs) and adenine base editors (ABEs), which are generally composed of an engineered deaminase and a catalytically impaired CRISPR-Cas9 variant, are new favorite tools for single base substitution in cells and organisms. In this review, we summarize the principle of base-editing systems and elaborate on the evolution of different platforms of CBEs and ABEs, including their deaminase, Cas9 variants, and editing outcomes. Moreover, we highlight their applications in mouse and human cells and discuss the challenges and prospects of base editors. The ABEand CBE systems have been used in gene silencing, pathogenic gene correction, and functional genetic screening. Single base editing is becoming a new promising genetic tool in biomedical research and gene therapy.

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Genetic Modulation of RNA Splicing with a CRISPR-Guided Cytidine Deaminase

Cited by 131 publications

References 49 publications

Chromosome Transplantation: A Possible Approach to Treat Human X-linked Disorders

Chromosome Transplantation: A Possible Approach to Treat Human X-linked Disorders

Genome Editing for the Understanding and Treatment of Inherited Cardiomyopathies

Single‐nucleotide editing: From principle, optimization to application

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