Basic Principles and Clinical Applications of CRISPR-Based Genome Editing

Abstract

Advances in sequencing technologies have facilitated the discovery of previously unknown genetic variants in both inherited and acquired disorders, and tools to correct these pathogenic variants are rapidly evolving. Since the first introduction of CRISPR-Cas9 in 2012, the field of CRISPR-based genome editing has progressed immensely, giving hope to many patients suffering from genetic disorders that lack effective treatment. In this review, we will examine the basic principles of CRISPR-based genome editing, explain the mechanisms of new genome editors, including base editors and prime editors, and evaluate the therapeutic possibilities of CRISPR-based genome editing by focusing on recently published clinical trials and animal studies. Although efficacy and safety issues remain a large concern, we cannot deny that CRISPR-based genome editing will soon be prevalent in clinical practice.

Impaired activity of the fusogenic micropeptide Myomixer causes myopathy resembling Carey-Fineman-Ziter syndrome

“…However, MYMX expression is strictly restricted to myoblast fusion ( 5 ), and studies in mice suggest that overexpression of muscle fusogens could negatively impact muscle fiber integrity in dystrophic conditions ( 42 ). Recently, CRISPR/Cas9 base editing has emerged as an attractive therapeutic genome editing tool to directly correct disease-causing mutations and maintain endogenous expression levels of the corrected genes ( 53 ). Several studies have shown that in vivo delivery of base editors by adeno-associated viruses can target specific tissues, edit target genes, restore gene function, and ameliorate a broad spectrum of pathologies, including muscular dystrophies, metabolic disorders, and hereditary blindness ( 53 ).…”

“…Recently, CRISPR/Cas9 base editing has emerged as an attractive therapeutic genome editing tool to directly correct disease-causing mutations and maintain endogenous expression levels of the corrected genes ( 53 ). Several studies have shown that in vivo delivery of base editors by adeno-associated viruses can target specific tissues, edit target genes, restore gene function, and ameliorate a broad spectrum of pathologies, including muscular dystrophies, metabolic disorders, and hereditary blindness ( 53 ). Using patient-derived iPSC myotubes, we show that the MYMX R46* variant is amenable to therapeutic correction by base editing.…”

Viral vectors and extracellular vesicles: innate delivery systems utilized in CRISPR/Cas-mediated cancer therapy

“…This approach is carried out by a process called intein-mediated trans-splicing, which to some degree is similar to mRNA splicing [ 83 , 84 ]. This method has been used to deliver base and prime editing systems, which were found to be quite promising [ 85 , 86 ]. Another challenging issue for in vivo delivery is the pre-existing immunogenicity against the bacterial Cas9 protein and AAV capsid.…”

Common strategies in silkworm disease resistance breeding research

“…The basic model consists of three steps: acquisition, expression, and intervention. [27][28][29] The CRISPR-Cas system is divided into two categories depending on the structure and evolutionary relationship of the Cas protein. There are six types of Cas, the most common being: Cas3 (Type I), Cas9 (Type II), Cas10 (Type III), Csf1 (Type IV), Cpf1/ Cas12 (Type V), and Cas13 (Type VI).…”