The delivery of small regulatory RNAS by gold nanoparticles

McCully, Mark Alan (2015) The delivery of small regulatory RNAS by gold nanoparticles. PhD thesis, University of Glasgow.

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Abstract

The traditional paradigm relying on drug discovery to treat and heal the body is changing. Medicine for the 21st century is moving towards using the body’s internal language of DNA and RNA to cure disease and repair injuries to the body.

We now appreciate the complexity of signalling through the genome and its transcribed RNA. The role of micro RNAs and short interfering RNAs are gaining much interest as potential therapeutics. This interest has been sparked by the discovery that the dysregulation of micro RNAs is the origin for a spectrum of diseases from cancer through to osteoporosis.

Small regulatory RNAs have been shown to influence stem cell maintenance, proliferation and differentiation, offering the potential to produce new tissue by manipulating RNA levels. However delivery of these molecules is fraught with difficulties. Without protection these molecules are quickly degraded in vivo and in vitro before reaching their intended target. With this in mind, this thesis aims to investigate the potential role for gold nanoparticles to deliver small regulatory RNAs and in turn produce a non-toxic and physiologically significant effect upon the cells. Initial investigations revealed the importance of PEG density and AuNP concentration; with lower PEG densities, allowing attached therapeutic siRNA against C-Myc to reduce C-Myc protein levels and cell proliferation. Subsequently we determined that modulating the expression of osteo-suppressive miRNA, with a nucleic antagonist sequence was able to influence osteogenesis in two cell models (MG63s and hMSCs). This thesis has shown that AuNPs can be used to effectively deliver therapeutically active small molecules to cells in vitro.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Gold nanoparticles, RNAi, siRNA, miRNA, cancer, stem cells, nanomedicine.
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
R Medicine > RM Therapeutics. Pharmacology
Colleges/Schools: College of Medical Veterinary and Life Sciences
Funder's Name: UNSPECIFIED
Supervisor's Name: Berry, Dr. Catherine and Dalby, Professor Matthew
Date of Award: 2015
Depositing User: Dr Mark McCully
Unique ID: glathesis:2015-6478
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 15 Jun 2015 13:08
Last Modified: 17 Jun 2015 10:26
URI: http://theses.gla.ac.uk/id/eprint/6478

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