title: Oligo/polynucleotide-based gene modification: strategies and therapeutic potential.
abstract: Oligonucleotide- and polynucleotide-based gene modification strategies were developed as an alternative to transgene-based and classical gene targeting-based gene therapy approaches for treatment of genetic disorders. Unlike the transgene-based strategies, oligo/polynucleotide gene targeting approaches maintain gene integrity and the relationship between the protein coding and gene-specific regulatory sequences. Oligo/polynucleotide-based gene modification also has several advantages over classical vector-based homologous recombination approaches. These include essentially complete homology to the target sequence and the potential to rapidly engineer patient-specific oligo/polynucleotide gene modification reagents. Several oligo/polynucleotide-based approaches have been shown to successfully mediate sequence-specific modification of genomic DNA in mammalian cells. The strategies involve the use of polynucleotide small DNA fragments, triplex-forming oligonucleotides, and single-stranded oligodeoxynucleotides to mediate homologous exchange. The primary focus of this review will be on the mechanistic aspects of the small fragment homologous replacement, triplex-forming oligonucleotide-mediated, and single-stranded oligodeoxynucleotide-mediated gene modification strategies as it relates to their therapeutic potential.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of California , San Francisco, California 94115, USA.
authors.forename: R Geoffrey
authors.initials: RG
authors.lastname: Sargent
authors.forename: Soya
authors.initials: S
authors.lastname: Kim
authors.forename: Dieter C
authors.initials: DC
authors.lastname: Gruenert
mesh_terms: D004247:DNA / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D004277:DNA, Single-Stranded / Q000235:genetics; D018390:Gene Targeting / Q000379:methods; D015316:Genetic Therapy; D006801:Humans; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D009841:Oligonucleotides / Q000235:genetics* / Q000627:therapeutic use*
chemical_list: D004277:DNA, Single-Stranded; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides; C051802:triplex DNA; D004247:DNA