Thesis (Ph. D.)--Ohio State University, 2005. / Document formatted into pages; contains 375 p. Includes bibliographical references. Abstract available online via OhioLINK's ETD Center; full text release delayed at author's request until 2006 March 9.

Antisense oligonucleotides are short strands of DNA, which bind to their complementary mRNA target to prevent protein translation. Although conceptually appealing, for their practical use as drugs, these oligonucleotides must have better cellular uptake, resistance to enzymatic degradation, and target selectivity. In this work, new synthetic chemistry is established to prepare a novel group of chemically modified oligonucleotides. The anionic phosphodiester backbone is partially replaced with a neutral triazole and, at the same time, the 2'-position of the ribose sugar is functionalised with pyrene, anthraquinone, or guanidine moieties. Being unnatural, the triazole backbone is inherently resistant to enzymatic degradation, while the reduced negative charge potentially improves cell penetration. The limitation of introduction of a triazole backbone into the antisense strand is its destabilising effect on the duplex formation with their complementary target. In this study, the 2'-modifications are used to restore the lost duplex stability and they have been found to be very efficient stabilising moieties. To evaluate the viability of this strategy, reporter gene assays based on splice-switching model are used. Promisingly, these modified oligonucleotides have successfully shown antisense splice-switching activity, suggesting there is further scope for their improvement.

Graduation date: 1991

published_or_final_version / Biochemistry / Master / Master of Philosophy

Thesis (M. Phil.)--University of Hong Kong, 1998. / Includes bibliographical references (leaves 106-115).

Thesis (Ph. D.)--Rutgers University, 2008. / "Graduate Program in Chemical and Biochemical Engineering." Includes bibliographical references (p. 129-137).

Thesis (Ph. D.)--West Virginia University, 2002. / Title from document title page. Document formatted into pages; contains xii, 161 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 140-158).

Bibliography: leaves 175-186. / 186 leaves : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Aims to examine the AP in A. thaliana and to produce an inducible antisense plant to assist future studies of the role of AOX. / Thesis (Ph.D.)--University of Adelaide, Dept. of Botany, 1999?

Thesis (Ph. D.)--University of New South Wales, 2000. / Also available online.

Thesis (Ph. D.)--Ohio State University, 2005. / Title from first page of PDF file. Includes bibliographical references (p. 167-181).