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Gene Targeting by Triple Helix‐Forming Oligonucleotides
Author(s) -
MAJUMDAR ALOKES,
PURI NITIN,
McCOLLUM NICHOLAS,
RICHARDS SALLY,
CUENOUD BERNARD,
MILLER PAUL,
SEIDMAN MICHAEL M.
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1281.013
Subject(s) - triple helix , oligonucleotide , chromatin , gene targeting , mutagenesis , chromatin remodeling , biology , gene , transgene , computational biology , dna , microbiology and biotechnology , genetics , mutation
A bstract : Effective gene targeting reagents would have widespread utility for genomic manipulation including transgenic cell and animal construction and for gene therapy. They would also be useful in basic research as probes of chromatin structure, and as tools for studying the repair and mutagenesis of targeted DNA damage. We are developing triple helix‐forming oligonucleotides (TFOs) for gene targeting in living mammalian cells. Challenges to TFO bioactivity include the impediments to the biochemistry of triplex formation presented by the physiological environment and the charge repulsion between the duplex and the third strand. In addition, there are biological constraints to target access imposed by mammalian chromatin structure. Here we describe the oligonucleotide modification format that appears to support biological activity of TFOs. In addition we show that manipulation of the cell biology, specifically the cell cycle, has a dramatic influence on TFO bioactivity.