Synthesis of oligonucleotide-based RNase H1-sensitive structures: a strategy with potential in breast cancer therapy and nanotechnology
| Autor: | Torrents Lara, Maria |
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| Přispěvatelé: | Terrazas Martínez, Montserrat |
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Popis: | Treballs Finals de Grau de Química, Facultat de Química, Universitat de Barcelona, Any: 2023, Tutora: Montserrat Terrazas Martinez The rising number of drug resistance cases, as well as untreatable illnesses by current approved therapies has encouraged the development of innovative therapeutic alternatives. This project explores the field of oligonucleotide-based drugs as a promising strategy to tackle current medical challenges, focusing special attention on antisense oligonucleotides (ASO) as therapeutic agents. These short single-stranded DNA polymers can be designed to bind to a specific disease-related mRNA. The resulting DNA·RNA heteroduplex triggers the activity of the endogenous enzyme RNase H, which specifically cleaves mRNA and thereby, inhibits gene expression. Here, a 3ASO multi-target structure which can simultaneously silence three genes involved in breast cancer drug resistance is assessed as a RNase H substrate. RNase H-sensitive systems are not only relevant in medicine but also in nanotechnology. This work also explores the suitability of oligonucleotides as building blocks of responsive self-assembled materials controlled by enzymatic reactions. To accomplish these aims, the 3ASO structure and the oligonucleotides building blocks are synthesised by means of two different automated solid-phase synthesizers: an ABI 3400 system and a last generation and low-consuming K&A S-4-LC model. Upon purification and hybridization, their ability to trigger RNase H activity is evaluated and further studied by PAGE |
| Databáze: | OpenAIRE |
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