CRISPR iPSC Cell line

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KO iPSC Cell line | Combining hiPSCs with CRISPR

KO iPSC Cell line | Combining hiPSCs with CRISPR

The past decade has seen the birth of two incredibly useful biological tools. The first is human-induced pluripotent stem cells (iPSCs), which can, in turn, be coaxed to become nearly any cell type. The second tool is the CRISPR/Cas9 system, which allows easy and precise editing of any region of the genome. The combination of hiPSCs and CRISPR/Cas9 genome editing provides an ability to repair putative causative alleles in patient lines, or introduce disease alleles into a healthy “WT” cell line.

Mutations in the genes PARK2 (parkin) cause autosomal recessive familial Parkinson’s disease. In this study, human iPSCs with PARK2 knockout introduced by genome editing have enabled investigations of parkin dysfunction in human dopaminergic neurons in vitro. This research identified and quantified more than half of all reported mitochondrial proteins and determined large numbers of dysregulated proteins in PARK2 KO neurons compared to healthy isogenic controls. Structural and functional analyses revealed an increase in mitochondrial area and the presence of elongated mitochondria as well as impaired glycolysis and lactate-supported respiration, leading to impaired cell survival in PARK2 KO neurons. This adds valuable insight into the effect of parkin dysfunction in human neurons and provides knowledge of disease-related pathways that can potentially be targeted for therapeutic intervention.

Develop a genome modified iPSC with Ubigene today! Ubigene developed CRISPR-UTM (based on CRISPR/Cas9 technology) which is more efficient than general CRISPR/Cas9 in double-strand breaking, and CRISPR-UTM can greatly improve the efficiency of homologous recombination.


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Reference:
Bogetofte, Helle, et al. "PARK2 mutation causes metabolic disturbances and impaired survival of human iPSC-derived neurons." Frontiers in cellular neuroscience 13 (2019): 297.

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