Gene Targeting by Triple Helix-Forming Oligonucleotides
| Autor: | Alokes Majumdar, Nicholas McCOLLUM, Sally Richards, Michael M. Seidman, Paul S. Miller, Nitin Puri, Bernard Cuenoud |
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| Rok vydání: | 2003 |
| Předmět: |
Genetic Markers
Genetics Hypoxanthine Phosphoribosyltransferase DNA damage Oligonucleotide General Neuroscience Transgene Genetic enhancement Cell Cycle Gene targeting DNA Cell cycle Biology General Biochemistry Genetics and Molecular Biology Cell biology Chromatin Cross-Linking Reagents Oligodeoxyribonucleotides History and Philosophy of Science Gene Targeting Animals Humans Triple helix |
| Zdroj: | Annals of the New York Academy of Sciences. 1002:141-153 |
| ISSN: | 1749-6632 0077-8923 |
| DOI: | 10.1196/annals.1281.013 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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