AUTHOR=Pavani Giulia , Amendola Mario TITLE=Targeted Gene Delivery: Where to Land JOURNAL=Frontiers in Genome Editing VOLUME=2 YEAR=2021 URL=https://www.frontiersin.org/journals/genome-editing/articles/10.3389/fgeed.2020.609650 DOI=10.3389/fgeed.2020.609650 ISSN=2673-3439 ABSTRACT=

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.