Gene editing and its applications in biomedicine

Li, Guanglei; Li, Xiangyang; Zhuang, Songkuan; Wang, Liren; Zhu, Yifan; Chen, Yangcan; Sun, Wen; Wu, Zeguang; Zhou, Zhuo; Chen, Jia; Huang, Xingxu; Wang, Jin; Li, Dali; Wei, Li; Wang, Haoyi; Wei, Wensheng

doi:10.1007/s11427-021-2057-0

Cited by 45 publications

(16 citation statements)

References 490 publications

(629 reference statements)

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“…Animal models are crucial for disease research, and CRISPR/Cas9 has become a widely used tool in creating animal disease models [28]. Three main methods exist for producing animal models: embryo microinjection, somatic cell nuclear transfer, and in situ injection.…”

Section: Animal Disease Models Mediated By Base Editingmentioning

confidence: 99%

The research progress of correcting pathogenic mutations by base editing

Li,

Zhang,

Huang

2024

Obstetrics and Gynecology

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Over 6500 Mendelian disorders have been documented, with approximately 4500 genes linked to these conditions. The majority of inherited diseases present in childhood and, currently, lack effective treatments, which imposes significant economic and psychological burdens on families and society. Gene editing, particularly base editing, offers an effective and safe strategy for repairing pathogenic point mutations. It has the potential to become a treatment, even a cure, for rare diseases. Currently, multiple gene editing-related drugs have entered clinical trials. In this chapter, we summarize the various gene editing systems, including CRISPR/Cas, base editing, and prime editing. We then focus on the current research progress of base editing in correcting pathogenic mutations. This includes applications such as building animal models, correcting mutations in various diseases, germline cell editing, delivery methods, and approved clinical trials. Finally, we discuss current challenges related to delivery methods, efficiency, precision, and cost.

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Section: Animal Disease Models Mediated By Base Editingmentioning

confidence: 99%

The research progress of correcting pathogenic mutations by base editing

Li,

Zhang,

Huang

2024

Obstetrics and Gynecology

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“…SpCas9 requires an NGG PAM for target DNA recognition and binding; this PAM requirement restricts the target space of SpCas9 to every 8 bp on average in the human genome (66). To broaden the targeting scope of BEs, other Cas orthologs and engineered Cas variants recognizing different PAMs have been incorporated into BEs (75,(89)(90)(91)(92)(93)(94). Among Cas orthologs, SaCas9 and ScCas9 are two smaller Cas9 proteins, and BEs developed with these homologs should be easier to deliver in vivo (75,93).…”

Section: Improvements Made For Precise Base Editingmentioning

confidence: 99%

“…To broaden the targeting scope of BEs, other Cas orthologs and engineered Cas variants recognizing different PAMs have been incorporated into BEs (75,(89)(90)(91)(92)(93)(94). Among Cas orthologs, SaCas9 and ScCas9 are two smaller Cas9 proteins, and BEs developed with these homologs should be easier to deliver in vivo (75,93). Engineered SpCas9 variants VQR-Cas9, EQR-Cas9, VRER-Cas9, xCas9, SpCas9-NG, and Cas9-SpRY with alternative PAMs have been employed to develop BEs (89)(90)(91)(92).…”

Section: Improvements Made For Precise Base Editingmentioning

confidence: 99%

Advances in CRISPR/Cas gene therapy for inborn errors of immunity

Liu

et al. 2023

Front. Immunol.

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Inborn errors of immunity (IEIs) are a group of inherited disorders caused by mutations in the protein-coding genes involved in innate and/or adaptive immunity. Hematopoietic stem cell transplantation (HSCT) is a mainstay definitive therapy for many severe IEIs. However, the lack of HLA-matched donors increases the risk of developing severe immunological complications. Gene therapy provides long-term clinical benefits and could be an attractive therapeutic strategy for IEIs. In this review, we describe the development and evolution of clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated proteins (Cas) gene-editing systems, including double-strand break (DSB)-based gene editing and DSB-free base editing or prime editing systems. Here, we discuss the advances in and issues associated with CRISPR/Cas gene editing tools and their potential as therapeutic alternatives for IEIs. We also highlight the progress of preclinical studies for the treatment of human genetic diseases, including IEIs, using CRISR/Cas and ongoing clinical trials based on this versatile technology.

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“…By selectively favoring a particular DNA repair pathway and the corresponding repair outcomes, different gene editing strategies can achieve different forms of genome manipulation [ 12 ]. Gene/enhancer disruption, intron/exon deletion, mutation correction, and targeted gene insertion, have all been reported, in preclinical models, to produce therapeutic benefits [ 13 ]. Among these advances, gene insertion entails the integration of a large sequence into the host genome to restore normal function.…”

Section: Introductionmentioning

confidence: 99%

Targeted Gene Insertion: The Cutting Edge of CRISPR Drug Development with Hemophilia as a Highlight

Zhang,

Wong

et al. 2024

BioDrugs

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The remarkable advance in gene editing technology presents unparalleled opportunities for transforming medicine and finding cures for hereditary diseases. Human trials of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease (Cas9)-based therapeutics have demonstrated promising results in disrupting or deleting target sequences to treat specific diseases. However, the potential of targeted gene insertion approaches, which offer distinct advantages over disruption/deletion methods, remains largely unexplored in human trials due to intricate technical obstacles and safety concerns. This paper reviews the recent advances in preclinical studies demonstrating in vivo targeted gene insertion for therapeutic benefits, targeting somatic solid tissues through systemic delivery. With a specific emphasis on hemophilia as a prominent disease model, we highlight advancements in insertion strategies, including considerations of DNA repair pathways, targeting site selection, and donor design. Furthermore, we discuss the complex challenges and recent breakthroughs that offer valuable insights for progressing towards clinical trials.

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Gene editing and its applications in biomedicine

Cited by 45 publications

References 490 publications

The research progress of correcting pathogenic mutations by base editing

The research progress of correcting pathogenic mutations by base editing

Advances in CRISPR/Cas gene therapy for inborn errors of immunity

Targeted Gene Insertion: The Cutting Edge of CRISPR Drug Development with Hemophilia as a Highlight

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