Approaches to Enhance Precise CRISPR/Cas9-Mediated Genome Editing.
Christopher E DenesAlexander J ColeYagiz Alp AksoyGeng LiGraham Gregory NeelyDaniel HesselsonPublished in: International journal of molecular sciences (2021)
Modification of the human genome has immense potential for preventing or treating disease. Modern genome editing techniques based on CRISPR/Cas9 show great promise for altering disease-relevant genes. The efficacy of precision editing at CRISPR/Cas9-induced double-strand breaks is dependent on the relative activities of nuclear DNA repair pathways, including the homology-directed repair and error-prone non-homologous end-joining pathways. The competition between multiple DNA repair pathways generates mosaic and/or therapeutically undesirable editing outcomes. Importantly, genetic models have validated key DNA repair pathways as druggable targets for increasing editing efficacy. In this review, we highlight approaches that can be used to achieve the desired genome modification, including the latest progress using small molecule modulators and engineered CRISPR/Cas proteins to enhance precision editing.
Keyphrases
- crispr cas
- dna repair
- genome editing
- dna damage
- small molecule
- genome wide
- dna damage response
- endothelial cells
- high glucose
- big data
- copy number
- oxidative stress
- dna methylation
- gene expression
- human health
- risk assessment
- drug induced
- protein protein
- deep learning
- insulin resistance
- transcription factor
- artificial intelligence
- pluripotent stem cells
- bioinformatics analysis
- weight loss