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Title: Capillary electrophoresis and the analysis of modified DNA oligonucleotides
Author: DeDionisio, Lawrence A.
ISNI:       0000 0004 7653 0972
Awarding Body: Ulster University
Current Institution: Ulster University
Date of Award: 2016
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Endogenous regulation of gene expression through sequence specific hybridization of complimentary oligodeoxynucleotides (ODNs) occurs within both prokaryotic and eukaryotic cells. These short segments of DNA are often referred to as antisense ODNs based on their binding to the target sequence defined as the sense strand. As early as 1978 it was recognized that antisense ODNs could be employed within a virus to effectively inhibit the translation of targeted RNA and essentially shut down viral transmission. With the advent of the automated synthesis of nucleic acids, it became feasible to develop antisense ODNs on a large scale, and the field of antisense therapeutics was born. Increased interest and development of antisense therapeutics together with advances in the field of nucleic acid synthesis in general fueled the need for a different approach to the quantitative analysis of ODNs. Furthermore, due to the fact that unmodified DNA within a cell is subject to nuclease degradation, chemical modifications of antisense ODNs were soon incorporated into the DNA molecule to garner nuclease resistance. Certain of these chemical modifications such as the phosphorothioate modification to the DNA backbone presented a challenge to standard separation techniques such as high performance liquid chromatography (HPLC). The research for this thesis was conducted during the 1990s when capillary electrophoresis (CE) or more specifically capillary gel electrophoresis (CGE) was investigated as an alternative to standard separation techniques such as such as polyacrylamide gel electrophoresis (PAGE) and HPLC. In this synopsis, it will be demonstrated that initial research and development of the methods described herein continue to impact CE and CGE in conjunction with the discovery, design, and characterization of both antisense ODNs and the analysis of nucleic acids. Keywords: Capillary gel electrophoresis -Antisense therapeutics- Phosphorothioate oligodeoxynucleotide • N3'—> P5' phosphoramidate.
Supervisor: Moore, Tara ; Nesbit, Andrew ; Hassan, David Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available