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Title: Towards understanding and applications of antisense oligonucleotides
Authors: Nguyen, Le Tuan Anh
Keywords: Science::Medicine::Pharmacy::Pharmaceutical technology
Science::Biological sciences::Biophysics
Issue Date: 2020
Publisher: Nanyang Technological University
Source: Nguyen, L. T. A. (2020). Towards understanding and applications of antisense oligonucleotides. Doctoral thesis, Nanyang Technological University, Singapore.
Abstract: Antisense oligonucleotides (ASOs), which are synthetic single-stranded nucleic acids, could enter living cells, hybridize to RNAs and inhibit gene expression. This approach could potentially lead to desired alterations of cellular characteristics, and has been under intensive investigations. This thesis aims to build a model towards the molecular mechanisms of ASO, and develop some therapeutic ASOs. The effects of various cellular and molecular conditions on the ASO efficacy are modelled by mathematical equations and practical experimentations. Particularly, three aspects are investigated separately, namely (i) the competition of productive and non-productive ASO uptake, (ii) the ASO sequestration by intracellular proteins, and (iii) the extent of mRNA expression. The unknown amount of functional ASOs delivered into the cells was also estimated. These findings enhance our understanding on antisense oligonucleotide therapeutics, potentially contributing to the discovery of more advanced ASO generations in the future. Finally, ASOs against two gene targets of interest, responsible for autoimmune disease and cancer, respectively, have been developed, showing promising therapeutic outcomes.
DOI: 10.32657/10356/145300
Schools: School of Physical and Mathematical Sciences 
Rights: This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
Fulltext Permission: embargo_20241222
Fulltext Availability: With Fulltext
Appears in Collections:SPMS Theses

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