Targeted Gene Delivery: Where to Land

• Main Authors: Giulia Pavani, Mario Amendola
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-01-01
• Series: Frontiers in Genome Editing
• Subjects: genome editing; gene therapy; nuclease; CRISPR; targeted integration (TI); knock-in
• Online Access: https://www.frontiersin.org/articles/10.3389/fgeed.2020.609650/full

Genome-editing technologies have the potential to correct most genetic defects involved in blood disorders. In contrast to mutation-specific editing, targeted gene insertion can correct most of the mutations affecting the same gene with a single therapeutic strategy (gene replacement) or provide novel functions to edited cells (gene addition). Targeting a selected genomic harbor can reduce insertional mutagenesis risk, while enabling the exploitation of endogenous promoters, or selected chromatin contexts, to achieve specific transgene expression levels/patterns and the modulation of disease-modifier genes. In this review, we will discuss targeted gene insertion and the advantages and limitations of different genomic harbors currently under investigation for various gene therapy applications.