Specific mutations induced by triplex-forming oligonucleotides in mice

Citation
Km. Vasquez et al., Specific mutations induced by triplex-forming oligonucleotides in mice, SCIENCE, 290(5491), 2000, pp. 530-533
Citations number
23
Categorie Soggetti
Multidisciplinary,Multidisciplinary,Multidisciplinary
Journal title
SCIENCE
ISSN journal
00368075 → ACNP
Volume
290
Issue
5491
Year of publication
2000
Pages
530 - 533
Database
ISI
SICI code
0036-8075(20001020)290:5491<530:SMIBTO>2.0.ZU;2-Z
Abstract
Tripler-forming oligonucleotides (TFOs) recognize and bind to specific dupl ex DNA sequences and have been used extensively to modify gene function in cells. Although germ line mutations can be incorporated by means of embryon ic stem cell technology, little progress has been made toward introducing m utations in somatic cells of living organisms. Here we demonstrate that TFO s can induce mutations at specific genomic sites in somatic cells of adult mice. Mutation detection was facilitated by the use of transgenic mice bear ing chromosomal copies of the supF and cll reporter genes. Mice treated wit h a supF-targeted TFO displayed about fivefold greater mutation frequencies in the supF gene compared with mice treated with a scrambled sequence cont rol oligomer, No mutagenesis was detected in the control gene (cll) with ei ther oligonucleotide. These results demonstrate that site-specific, TFO-dir ected genome modification can be accomplished in intact animals.