Can Designer Indels Be Tailored by Gene Editing?

• Published in: BioEssays Vol. 41; no. 12
• Main Authors: Trimidal, Sara G., Benjamin, Ronald, Bae, Ji Eun, Han, Mira V., Kong, Elizabeth, Singer, Aaron, Williams, Tyler S., Yang, Bing, Schiller, Martin R.
• Format: Journal Article
• Language: English
• Published: Cambridge Wiley Subscription Services, Inc 01-12-2019
• Subjects: Binding; CRISPR/Cas9; Deoxyribonucleic acid; DNA; DNA damage; DNA repair; double strand break; gene editing; Gene expression; Genetic modification; Genomes; Insertion; Literature reviews; Maintenance; meganuclease; Non-homologous end joining; Nuclease; TALEN; Therapeutic applications; zinc finger nuclease
• ISSN: 0265-9247; 1521-1878
• DOI: 10.1002/bies.201900126

Genome editing with engineered nucleases (GEENs) introduce site‐specific DNA double‐strand breaks (DSBs) and repairs DSBs via nonhomologous end‐joining (NHEJ) pathways that eventually create indels (insertions/deletions) in a genome. Whether the features of indels resulting from gene editing could be customized is asked. A review of the literature reveals how gene editing technologies via NHEJ pathways impact gene editing. The survey consolidates a body of literature that suggests that the type (insertion, deletion, and complex) and the approximate length of indel edits can be somewhat customized with different GEENs and by manipulating the expression of key NHEJ genes. Structural data suggest that binding of GEENs to DNA may interfere with binding of key components of DNA repair complexes, favoring either classical‐ or alternative‐NHEJ. The hypotheses have some limitations, but if validated, will enable scientists to better control indel makeup, holding promise for basic science and clinical applications of gene editing. Also see the video here https://youtu.be/vTkJtUsLi3w
Gene editing with engineered nucleases introduce double‐strand breaks at specific DNA target sites. Error‐prone nonhomologous end‐joining (NHEJ) machinery repairs the lesion introducing indels. The length, type, and constitution of these indels can now be controlled by editing with different engineered nucleases or by manipulating expression of NHEJ genes.