Advantages of CRISPR-Cas9 combined organoid model in the study of congenital nervous system malformations

Abstract

In the past 10 years, gene-editing and organoid culture have completely changed the process of biology. Congenital nervous system malformations are difficult to study due to their polygenic pathogenicity, the complexity of cellular and neural regions of the brain, and the dysregulation of specific neurodevelopmental processes in humans. Therefore, the combined application of CRISPR-Cas9 in organoid models may provide a technical platform for studying organ development and congenital diseases. Here, we first summarize the occurrence of congenital neurological malformations and discuss the different modeling methods of congenital nervous system malformations. After that, it focuses on using organoid to model congenital nervous system malformations. Then we summarized the application of CRISPR-Cas9 in the organoid platform to study the pathogenesis and treatment strategies of congenital nervous system malformations and finally looked forward to the future.

Current trends and research topics regarding organoids: A bibliometric analysis of global research from 2000 to 2023

“…Recently, genome engineering such as CRISPR/Cas9 has been rapidly developed and applied to organoids. The combination of this technology with organoids could create new conditions for the study of organ development and the treatment of congenital diseases [ 99 ]. One of its advantages is the ability to facilitate the modelling of human cell-type diseases, like Mari Nakamura et al [ 100 ], who generated iPSC from patients and used CRISPR/Cas9 to insert MAPT genes to form frontotemporal family dementia (FTD) model and found that mutant tau proteins exhibited abnormalities such as reduced levels of phosphorylation.…”

Advanced Cellular Models for Rare Disease Study: Exploring Neural, Muscle and Skeletal Organoids

“…Bendriem et al used genome editing to knock out the gene Occludin (OCLN) in mouse and human models. OCLN KO resulted in early neuronal differentiation disorder, the slow self-renewal of progenitor cells and increased apoptosis in mice, whereas the human neural progenitor cells were seriously affected [56][57][58]. Leigh syndrome (LS) is another hereditary progressive neurodegenerative disease that leads to subacute necrotizing encephalomyelitis [56,57].…”

“…OCLN KO resulted in early neuronal differentiation disorder, the slow self-renewal of progenitor cells and increased apoptosis in mice, whereas the human neural progenitor cells were seriously affected [56][57][58]. Leigh syndrome (LS) is another hereditary progressive neurodegenerative disease that leads to subacute necrotizing encephalomyelitis [56,57]. Cell models of LS have been generated by using iPSCs from LS patients with a mutation in the gene for surfeit locus protein 1 (SURF1) to produce brain organoids.…”

Decoding Chiari Malformation and Syringomyelia: From Epidemiology and Genetics to Advanced Diagnosis and Management Strategies

“…Exploring Gene Therapy: Investigate the feasibility of gene therapy as a therapeutic approach for Chiari malformation and syringomyelia. Cutting-edge gene-editing tools like CRISPR/Cas9 present novel avenues for rectifying genetic mutations that cause diseases [80].…”