Towards a new era in medicine: therapeutic genome editing

Abstract

Genome editing is the process of precisely modifying the nucleotide sequence of the genome. It has provided a powerful approach to research questions but, with the development of a new set of tools, it is now possible to achieve frequencies of genome editing that are high enough to be useful therapeutically. Genome editing is being developed to treat not only monogenic diseases but also infectious diseases and diseases that have both a genetic and an environmental component.

Fig. 1

Nuclease-based genome editing creates a specific double-stranded break (DSB) in the genome and then allows the cell’s own endogenous repair machinery to repair the break. a When the editing of a single break occurs by nonhomologous end-joining (NHEJ), insertions/deletions are created at the site of the break. b When the editing of two DSBs occurs by NHEJ, chromosomal deletions, inversions or translocations can be created. c When editing of a single DSB occurs by homologous recombination (HR) using a provided donor sequence, precise changes in the nucleotide sequence ranging from a single base insertion to the introduction of a large cassette of genes can occur. Using NHEJ and HR mediated editing, it is now possible to inactivate genetic elements, create defined deletions ranging from a few bases to thousands of bases, and precise nucleotide changes to the sequence of the genome. AAV Adeno-associated virus, bps Basepairs, IDLV Integrase-deficient lentivirus