Gene augmentation has been the paradigm in the majority of gene therapy protocols but in recent years the potential of repairing the mutated gene in situ by targeted gene correction has become a reality. In fact, targeted gene repair has many advantages over conventional replacement strategies, notably the possibility to treat dominant as well as recessive disorders, and the small molecular size of the pharmacologically active agent. Chimeric RNA/DNA oligonucleotides, small fragment homologous replacement, as well as triplex-forming and single-stranded oligonucleotides are all examples of the growing armamentarium for gene repair, and are the subject of this review. In addition, we have also included a discussion of the reawakened Sleeping Beauty (SB) transposon system as a novel non-viral gene replacement strategy.
Bibliographical noteFunding Information:
Paul Richardson is supported by the Wellcome Trust; and Christian Thoma by the Deutsche Forschungsge-meinschaft. This work was funded in part by National Institutes of Health Grants P01 HD32652-06 (to B.T.K), P01 HL65578-01 and P01 HL55552-06 (to C.J.S.), and ValiGen, Inc. (to C.J.S.).
- Chimeric RNA/DNA oligonucleotides
- Gene correction
- Sleeping beauty transposon