title: An update on targeted gene repair in mammalian cells: methods and mechanisms.
abstract: Transfer of full-length genes including regulatory elements has been the preferred gene therapy strategy for clinical applications. However, with significant drawbacks emerging, targeted gene alteration (TGA) has recently become a promising alternative to this method. By means of TGA, endogenous DNA repair pathways of the cell are activated leading to specific genetic correction of single-base mutations in the genome. This strategy can be implemented using single-stranded oligodeoxyribonucleotides (ssODNs), small DNA fragments (SDFs), triplex-forming oligonucleotides (TFOs), adeno-associated virus vectors (AAVs) and zinc-finger nucleases (ZFNs). Despite difficulties in the use of TGA, including lack of knowledge on the repair mechanisms stimulated by the individual methods, the field holds great promise for the future. The objective of this review is to summarize and evaluate the different methods that exist within this particular area of human gene therapy research.
authors.affiliation: Institute of Human Genetics, The Bartholin Building, University of Aarhus, 8000 Aarhus C, Denmark.
authors.forename: Nanna M
authors.initials: NM
authors.lastname: Jensen
authors.forename: Trine
authors.initials: T
authors.lastname: Dalsgaard
authors.forename: Maria
authors.initials: M
authors.lastname: Jakobsen
authors.forename: Roni R
authors.initials: RR
authors.lastname: Nielsen
authors.forename: Charlotte B
authors.initials: CB
authors.lastname: Sørensen
authors.forename: Lars
authors.initials: L
authors.lastname: Bolund
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Jensen
mesh_terms: D000818:Animals; D004260:DNA Repair; D000229:Dependovirus; D018390:Gene Targeting / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D009838:Oligodeoxyribonucleotides
chemical_list: D009838:Oligodeoxyribonucleotides