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Title: Bio-reducible polyamines for siRNA delivery
Author: Serginson, James Michael
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2012
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Even though siRNA shows great promise in the treatment of genetic disease, cancer and viral infection; the lack of a suitable delivery vector remains a barrier to clinical use. Currently, viral vectors lead the field in terms of efficacy but are generally regarded as prohibitively dangerous. Synthetic alternatives such as cationic polymers could overcome this problem. Previous work in the group found that small, cationic, disulfide-containing, cyclic polyamines – despite being non-polymeric – were useful as vectors for pDNA transfection; this work focuses on adapting the material for siRNA. A branched analogue of the cyclic compounds was prepared and the synthetic procedures investigated are discussed. The suitability of both compounds for siRNA delivery was studied in depth. Characterisation of their interactions with nucleic acids under various conditions was carried out using light-scattering techniques, gel electrophoresis and fluorescent dye exclusion assays. Results from these experiments were used to allow successful use of the materials as vectors and enable understanding of the mechanism of the template-driven polymerisation. Early data concerning the efficacy of the materials as an siRNA delivery system in vitro was obtained using A549 lung carcinoma cells as a model system with siRNAs targeting the production of the enzyme GAPDH. Both compounds showed a hint of successful siRNA Delivery but the data was not overwhelmingly conclusive. Further experiments will be required to optimise the materials for maximum biological efficacy and to confirm they offer potential as a novel delivery system.
Supervisor: Thanou, Maya ; Steinke, Joachim Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available