The overal goal of the work is to develop and test novel genetic methods to test the hypothesis that triple helix forming oligonucleotides can be used to deliver site-selective DNA damage and mutation in mammalian cells.
The specific aims of the work are to develop new models to study triple helix- mediated mutagenesis (based upon shuttle vector technology), to investigate the physical parameters which affect targeted mutagenesis upon these shuttle vectors in vitro, to examine DNA damage and repair pathways which influence TFO mediated mutation, and finally to extend the work to study TFO mediated mutation in chromosomal genes of the mouse, rather than shuttle vectors.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA064186-04
Application #
2700561
Study Section
Chemical Pathology Study Section (CPA)
Program Officer
Pelroy, Richard
Project Start
1995-07-01
Project End
1999-04-30
Budget Start
1998-05-01
Budget End
1999-04-30
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Yale University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Chin, Joanna Y; Glazer, Peter M (2009) Repair of DNA lesions associated with triplex-forming oligonucleotides. Mol Carcinog 48:389-99
Lonkar, Pallavi; Kim, Ki-Hyun; Kuan, Jean Y et al. (2009) Targeted correction of a thalassemia-associated beta-globin mutation induced by pseudo-complementary peptide nucleic acids. Nucleic Acids Res 37:3635-44
Schleifman, Erica B; Chin, Joanna Y; Glazer, Peter M (2008) Triplex-mediated gene modification. Methods Mol Biol 435:175-90
Chin, Joanna Y; Kuan, Jean Y; Lonkar, Pallavi S et al. (2008) Correction of a splice-site mutation in the beta-globin gene stimulated by triplex-forming peptide nucleic acids. Proc Natl Acad Sci U S A 105:13514-9
Kim, Ki-Hyun; Nielsen, Peter E; Glazer, Peter M (2007) Site-directed gene mutation at mixed sequence targets by psoralen-conjugated pseudo-complementary peptide nucleic acids. Nucleic Acids Res 35:7604-13
Chin, Joanna Y; Schleifman, Erica B; Glazer, Peter M (2007) Repair and recombination induced by triple helix DNA. Front Biosci 12:4288-97
Knauert, Melissa P; Kalish, Jennifer M; Hegan, Denise C et al. (2006) Triplex-stimulated intermolecular recombination at a single-copy genomic target. Mol Ther 14:392-400
Knauert, Melissa P; Lloyd, Janice A; Rogers, Faye A et al. (2005) Distance and affinity dependence of triplex-induced recombination. Biochemistry 44:3856-64
Kalish, Jennifer M; Seidman, Michael M; Weeks, Daniel L et al. (2005) Triplex-induced recombination and repair in the pyrimidine motif. Nucleic Acids Res 33:3492-502
Rogers, Faye A; Manoharan, Muthiah; Rabinovitch, Peter et al. (2004) Peptide conjugates for chromosomal gene targeting by triplex-forming oligonucleotides. Nucleic Acids Res 32:6595-604

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