Thesis
Bioconjugation strategies for oligonucleotide functionalisation
- Abstract:
- Chemical modification of oligonucleotides has gained growing attention in research and therapeutic areas as these modalities, such as ribose modifications or fluorescent tags, have shown great promise to improve therapeutic properties and enable real-time analysis of biodistribution in antisense and RNA-based therapeutics. Recent development of modified nucleoside phosphoramidites and triphosphates enables the incorporation of modified functionalities and small-molecule conjugates onto synthetic oligos by solid-phase or enzymatic syntheses. Such approaches, however, may prove inadequate in certain applications where modifications on long oligos or specific inter-nucleosidic linkages are desired. In this thesis, we explored various solid-phase and solution-phase chemical approaches to access oligonucleotide bioconjugates that are challenging to access by conventional methods. These modalities include oligonucleotide dendrons and 3’-conjugates of long RNA. In addition, we examined their physical properties and biological functions, and discussed their potential applications.
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(Preview, Dissemination version, pdf, 7.8MB, Terms of use)
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Authors
Contributors
+ Brown, T
- Institution:
- University of Oxford
- Division:
- MPLS
- Department:
- Chemistry
- Sub department:
- Chemistry Research Laboratory
- Research group:
- Tom Brown
- Role:
- Supervisor
- ORCID:
- 0000-0002-6538-3036
+ Turberfield, A
- Institution:
- University of Oxford
- Division:
- MPLS
- Department:
- Physics
- Sub department:
- Condensed Matter Physics
- Role:
- Examiner
- ORCID:
- 0000-0002-3876-0190
+ Howorka, S
- Institution:
- University College London
- Role:
- Examiner
- ORCID:
- 0000-0002-6527-2846
+ Croucher Foundation
More from this funder
- Funder identifier:
- https://ror.org/04741mc34
- Programme:
- University of Oxford Croucher Scholarships
- DOI:
- Type of award:
- DPhil
- Level of award:
- Doctoral
- Awarding institution:
- University of Oxford
- Language:
-
English
- Keywords:
- Subjects:
- Deposit date:
-
2024-07-23
- ARK identifier:
Terms of use
- Copyright holder:
- Gerald Chik
- Copyright date:
- 2023
- Rights statement:
- The author of this thesis declares that the thesis titled “Bioconjugation strategies for oligonucleotide functionalisation” and the corresponding research presented in this thesis was performed and written by the author under the supervision of Professor Tom Brown at the University of Oxford. All experiments, except oligonucleotide synthesis which was conducted by Prof. Afaf El-Sagheer, were conducted by the author. The research is original and has not been submitted in full or in part for any other degree at this or at any other university. The copyright of this thesis rests with the author. Figures generated and licensed by third-party provider are acknowledged in relevant sections.
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