Genome editing using CRISPR/Cas9 to treat hereditary hematological disorders

Abstract

The clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system is a versatile and convenient genome-editing tool with prospects in gene therapy. This technique is based on customized sitespecific nucleases with programmable guiding RNAs that cleave and introduce double-strand breaks (DSBs) at the target locus and achieve precise genome modification by triggering DNA repair mechanisms. Human hematopoietic stem/ progenitor cells (HSPCs) are conventional cell targets for gene therapy in hematological diseases and have been widely used in most studies. Induced pluripotent stem cells (iPSCs) can be generated from a variety of somatic cells and hold great promise for personalized cell-based therapies. CRISPR/Cas9-mediated genome editing in autologous HSPCs and iPSCs is an ideal therapeutic solution for treating hereditary hematological disorders. Here, we review and summarize the latest studies about CRISPR/Cas9-mediated genome editing in patient-derived HSPCs and iPSCs to treat hereditary hematological disorders. Current challenges and prospects are also discussed.

Nucleic acid degradation as barrier to gene delivery: a guide to understand and overcome nuclease activity

“…Due to the precise genome modification at a specific DNA locus, CRISPR/Cas9 has been extensively studied in a variety of diseases, such as cancer and hereditary hematological disorders. 136,137 Currently, other CRISPR-Cas systems targeting RNA, such as the Cas13 family, have also demonstrated some exciting outcomes, such as mRNA knockdown, mRNA live imaging, RNA base editing, cleavage of viral RNAs within mammalian cells, reduction of influenza viruses and SARS-CoV-2. 138,139 For a more elaborated overview on genome-editing nucleases, the reader is referred to recent publications.…”

CRISPR technology in human diseases

“…iPSCs could be generated from various somatic cells with significant potential in personalized cell therapy. 227 Correction of pathogenic iPSC mutations can restore function and provide an abundant source of cells for transplantation. Therefore, genome editing of autologous HSPCs and iPSCs mediated by CRISPR–Cas9 is a therapeutic option ideal for treating inherited hematologic diseases.…”

CRISPR-Based Gene Editing in Acinetobacter baumannii to Combat Antimicrobial Resistance

“…The cas gene encodes the Cas protein or nuclease protein, which is responsible for the cleavage and destruction of foreign viral DNA [ 193 ]. Its features, namely that it is an affordable, rapid, accurate, effective, and efficient method of gene editing, make CRISPR-Cas most researched genome-editing tool in recent years, where it has demonstrated the ability to get rid of bacterial infections [ 194 , 195 ], correct genetic flaws [ 196 , 197 ], and eradicate dangerous infectious viruses [ 198 , 199 ].…”