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

Area of Science:

• Molecular Biology
• Genetics
• Biotechnology

Background:

• Genome editing technologies, such as those employing engineered nucleases (GEENs), introduce targeted DNA double-strand breaks (DSBs).
• These DSBs are primarily repaired through nonhomologous end-joining (NHEJ) pathways, resulting in genomic alterations known as insertions/deletions (indels).

Purpose of the Study:

• To investigate whether the characteristics of indels generated by gene editing can be precisely controlled.
• To review and consolidate existing literature on the impact of NHEJ pathways on gene editing outcomes.

Main Methods:

• Literature review of studies on genome editing engineered nucleases (GEENs) and nonhomologous end-joining (NHEJ) pathways.
• Analysis of structural data regarding the interaction between GEENs, DNA, and DNA repair complexes.

Main Results:

• The type (insertion, deletion, complex) and approximate length of indels can be influenced by the choice of GEENs.
• Manipulation of key NHEJ gene expression levels can also modulate indel characteristics.
• GEEN binding to DNA may alter the recruitment of DNA repair factors, potentially favoring classical or alternative NHEJ pathways.

Conclusions:

• Controlling indel features in gene editing is achievable to some extent.
• Understanding the interplay between GEENs and NHEJ pathways offers potential for refining gene editing precision.
• Validated hypotheses could significantly enhance control over indel outcomes for basic research and clinical applications.