Can Designer Indels Be Tailored by Gene Editing?: Can Indels Be Customized?

• Published in: BioEssays 2019-12, Vol.41 (12), p.e1900126-e1900126
• 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: Article
• Language: English
• Subjects: CRISPR-Cas Systems - genetics; DNA - genetics; DNA - metabolism; DNA Breaks, Double-Stranded; Gene Editing - methods; Humans; Transcription Activator-Like Effector Nucleases - metabolism; Zinc Finger Nucleases - metabolism
• ISSN: 0265-9247; 1521-1878; 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 abstract here https://youtu.be/vTkJtUsLi3w.