| Summary: | 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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