Progress and prospects: targeted gene alteration (TGA)

Targeted gene repair or targeted gene alteration is a molecular strategy that aims to correct single base mutations responsible for genetic diseases. The concept involves using single-stranded DNA oligonucleotides to direct a nucleotide exchange reaction at the genomic site of the mutation. Investigators have made significant progress in elucidating the mechanism(s) by which the mutation is corrected and have begun to focus on several viable targets that show great potential for clinical application. During the past several years, the field has witnessed a phase transition as the focus has switched from purely basic science to a sustained translational mode. We highlight the important advances over the last two to three years, some of which have moved the technology closer to the clinic while some others have introduced new reasons for caution.