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.