Quarterly Reviews of Biophysics 35, 1 (2002), pp. 89–107.  2002 Cambridge University Press DOI : 10.1017/S0033583502003773 Printed in the United Kingdom 89 Triplex-forming oligonucleotides : principles and applications Karen M. Vasquez 1 and Peter M. Glazer 2, * 1 Department of Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Science Park Research Division, Smithville, TX 78957, USA 2 Departments of Therapeutic Radiology and Genetics, Yale University School of Medicine, New Haven, CT 06520-8040, USA 1. Triple-helical nucleic acids 89 1.1 History 89 1.2 Use of oligomers in triplex formation 90 2. Modes of triplex formation 90 2.1 Intermolecular triplexes 90 2.2 Intramolecular triplexes (H-DNA) 92 2.3 R-DNA (recombination DNA) 92 2.4 PNA (peptide nucleic acids) 93 3. Triplex structural models 93 3.1 YR-Y triplexes 94 3.2 GT-A base triplets 94 3.3 TC-G base triplets 94 3.4 TA-T and C + G-C base triplets 94 3.5 RR-Y triplexes 94 4. Modifications of TFOs 95 4.1 Backbone modification of oligonucleotides 95 4.2 Modification of the ribose in oligonucleotides 96 4.3 Base modification of oligonucleotides 97 5. Gene targeting and modification via triplex technology 98 5.1 Transcription and replication inhibition 99 5.2 TFO-directed mutagenesis 99 5.3 TFO-induced recombination 100 5.4 Future challenges in triplex-directed genome modification 100 6. References 101 1. Triple-helical nucleic acids 1.1 History The first description of triple-helical nucleic acids was by Felsenfeld and Rich in 1957 (Felsenfeld et al. 1957). While studying the binding characteristics of polyribonucleotides by * Author to whom correspondence should be addressed : BCMM 354, 295 Congress Ave, New Haven, CT 06536, USA. Tel. : 203-737-2788 ; Fax : 203-737-2630 ; E-mail : peter.glazeryale.edu