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Modified oligonucleotides target the IRES in c-Myc to control gene expression

Modified oligonucleotides target the IRES in c-Myc to control gene expression
Modified oligonucleotides target the IRES in c-Myc to control gene expression
Regulation of gene expression is attracting more attention as a means to develop gene
therapy for cancer, as it targets specifically cancer genes with no harm for healthy body
cells. Deregulation of c-Myc protein is found to occur in more than half of human tumours and correlates to aggressive cancer stages, with its resistance to therapy, making it very difficult to be cured by traditional cancer therapy. Controlling of gene expression could be a promising approach to regulate this oncoprotein, in particular, stopping the translation of the c-Myc mRNA.

Translation from mRNA to protein requires initiation, elongation and termination of the
peptide synthesis. Blocking the initiation factors, in particular binding of the ribosome to
the start site of mRNA, could be a way worth trying to stop translation.

The possible secondary structure of the c-Myc mRNA gives a potential new method to
control gene expression of mRNA. Apart from the common initiation sites, some mRNA
contains an internal ribosomal entry site (IRES) element, which is being better understood
in recent years. This could lead us to choose some more promising targets to control gene expression.

Oligonucleotides provide us a good resource to control the gene expression. Not only the
standard DNA, but in particular some modified oligonucleotides, including locked nucleic
acid (LNA) and phosphorothioate nucleic acid.

In this essay, we aimed to synthesise standard DNA and modified DNA, which target the
IRES point of the c-Myc gene to inhibit the translation process.
University of Southampton
Shi, Ting
2827b77a-3794-4be2-8d6d-04e831b3defe
Shi, Ting
2827b77a-3794-4be2-8d6d-04e831b3defe
Stulz, Eugen
9a6c04cf-32ca-442b-9281-bbf3d23c622d

Shi, Ting (2018) Modified oligonucleotides target the IRES in c-Myc to control gene expression. University of Southampton, Masters Thesis, 73pp.

Record type: Thesis (Masters)

Abstract

Regulation of gene expression is attracting more attention as a means to develop gene
therapy for cancer, as it targets specifically cancer genes with no harm for healthy body
cells. Deregulation of c-Myc protein is found to occur in more than half of human tumours and correlates to aggressive cancer stages, with its resistance to therapy, making it very difficult to be cured by traditional cancer therapy. Controlling of gene expression could be a promising approach to regulate this oncoprotein, in particular, stopping the translation of the c-Myc mRNA.

Translation from mRNA to protein requires initiation, elongation and termination of the
peptide synthesis. Blocking the initiation factors, in particular binding of the ribosome to
the start site of mRNA, could be a way worth trying to stop translation.

The possible secondary structure of the c-Myc mRNA gives a potential new method to
control gene expression of mRNA. Apart from the common initiation sites, some mRNA
contains an internal ribosomal entry site (IRES) element, which is being better understood
in recent years. This could lead us to choose some more promising targets to control gene expression.

Oligonucleotides provide us a good resource to control the gene expression. Not only the
standard DNA, but in particular some modified oligonucleotides, including locked nucleic
acid (LNA) and phosphorothioate nucleic acid.

In this essay, we aimed to synthesise standard DNA and modified DNA, which target the
IRES point of the c-Myc gene to inhibit the translation process.

Text
SHI Final Thesis for Award - Version of Record
Restricted to Repository staff only until 30 June 2021.
Available under License University of Southampton Thesis Licence.

More information

Published date: September 2018

Identifiers

Local EPrints ID: 433934
URI: http://eprints.soton.ac.uk/id/eprint/433934
PURE UUID: 2ab727ea-ba63-4979-b402-923631ecee19
ORCID for Eugen Stulz: ORCID iD orcid.org/0000-0002-5302-2276

Catalogue record

Date deposited: 06 Sep 2019 16:30
Last modified: 07 Sep 2019 00:35

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Contributors

Author: Ting Shi
Thesis advisor: Eugen Stulz ORCID iD

University divisions

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