Specific Mutations Induced by Triplex-Forming Oligonucleotides in Mice
Karen M. Vasquez,
Latha Narayanan,
Peter M. Glazer*
Triplex-forming oligonucleotides (TFOs) recognize and bind
to specific duplex DNA sequences and have been used extensively to
modify gene function in cells. Although germ line mutations can be
incorporated by means of embryonic stem cell technology, little
progress has been made toward introducing mutations in somatic cells of
living organisms. Here we demonstrate that TFOs can induce mutations at
specific genomic sites in somatic cells of adult mice. Mutation
detection was facilitated by the use of transgenic mice bearing
chromosomal copies of the supF and cII reporter
genes. Mice treated with a supF-targeted TFO displayed about
fivefold greater mutation frequencies in the supF gene
compared with mice treated with a scrambled sequence control oligomer. No mutagenesis was detected in the control gene (cII) with
either oligonucleotide. These results demonstrate that site-specific, TFO-directed genome modification can be accomplished in intact animals.
Departments of Therapeutic Radiology and Genetics, Yale University
School of Medicine, Boyer Center for Molecular Medicine, 295 Congress
Avenue, New Haven, CT 06536, USA.
*
To whom correspondence should be addressed. E-mail:
peter.glazer{at}yale.edu
