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Biodegradable dextran nanogels as functional carriers for the intracellular delivery of small interfering RNA

Koen Raemdonck UGent (2009)
abstract
RNA interference (RNAi) certainly is a hot topic among the scientific community, judging by the broad financial investments and the tremendous research output to date.[1] This statement is further illustrated through a PubMed search on the term ‘RNA interference’ (performed on June 15th 2009), which yielded ~16.500 entries. RNAi is a naturally conserved gene silencing mechanism functioning in eukaryotic cells and is activated by small interfering RNAs (siRNAs) that trigger the degradation of mRNA in a sequence‐specific manner. Besides its use as a laboratory tool in functional genomics and drug target discovery, the therapeutic potential of RNAi by blocking the production of disease‐causing proteins has also long been recognized. In conclusion, this thesis comprises a novel FRET based approach for the intracellular assessment of small interfering RNA (siRNA) integrity, which could aid in clarifying the correlation between intracellular siRNA fate and the eventual RNAi outcome. Besides siRNA stability, this thesis also describes the design of cationic and biodegradable nanogels for the time‐controlled delivery of siRNA. We provide evidence that these nanogels can effectively deliver active siRNA across the cellular barrier, leading to substantial and durable gene silencing. Endosomal escape is identified as the predominant barrier confining the full RNAi potential, opening up new opportunities to further improve this delivery concept. It is conceivable that, although RNAi can generally be applied to interfere with the expression of virtually any gene, several distinct in vivo delivery agents will be needed depending on the disease target and the chosen route of administration. Our nanogels may well claim a future position in this ensemble of siRNA delivery systems.
Please use this url to cite or link to this publication:
author
promoter
UGent and UGent
organization
alternative title
Biodegradeerbare dextraan nanogelen als functionele dragers voor de intracellulaire afgifte van small interfering RNA
year
type
dissertation (monograph)
subject
pages
235 pages
publisher
Ghent University. Faculty of Pharmaceutical Sciences
place of publication
Ghent, Belgium
defense location
Gent : Het Pand (zaal rector Blancquaert)
defense date
2009-10-08 17:00
language
English
UGent publication?
yes
classification
D1
additional info
dissertation in part contains copyrighted material
copyright statement
I have transferred the copyright for this publication to the publisher
id
766147
handle
http://hdl.handle.net/1854/LU-766147
alternative location
http://lib.ugent.be/fulltxt/RUG01/001/356/450/RUG01-001356450_2010_0001_AC.pdf
date created
2009-10-21 09:04:32
date last changed
2010-01-29 11:31:35
@phdthesis{766147,
  abstract     = {RNA interference (RNAi) certainly is a hot topic among the scientific community, judging by the broad financial investments and the tremendous research output to date.[1] This statement is further illustrated through a PubMed search on the term {\textquoteleft}RNA interference{\textquoteright} (performed on June 15th 2009), which yielded {\texttildelow}16.500 entries. RNAi is a naturally conserved gene silencing mechanism functioning in eukaryotic cells and is activated by small interfering RNAs (siRNAs) that trigger the degradation of mRNA in a sequence\unmatched{2010}specific manner. Besides its use as a laboratory tool in functional genomics and drug target discovery, the therapeutic potential of RNAi by blocking the production of disease\unmatched{2010}causing proteins has also long been recognized. 
In conclusion, this thesis comprises a novel FRET based approach for the intracellular assessment of small interfering RNA (siRNA) integrity, which could aid in clarifying the correlation between intracellular siRNA fate and the eventual RNAi outcome. Besides siRNA stability, this thesis also describes the design of cationic and biodegradable nanogels for the time\unmatched{2010}controlled delivery of siRNA. We provide evidence that these nanogels can effectively deliver active siRNA across the cellular barrier, leading to substantial and durable gene silencing. Endosomal escape is identified as the predominant barrier confining the full RNAi potential, opening up new opportunities to further improve this delivery concept. It is conceivable that, although RNAi can generally be applied to interfere with the expression of virtually any gene, several distinct in vivo delivery agents will be needed depending on the disease target and the chosen route of administration. Our nanogels may well claim a future position in this ensemble of siRNA delivery systems.},
  author       = {Raemdonck, Koen},
  language     = {eng},
  pages        = {235},
  publisher    = {Ghent University. Faculty of Pharmaceutical Sciences},
  school       = {Ghent University},
  title        = {Biodegradable dextran nanogels as functional carriers for the intracellular delivery of small interfering RNA},
  url          = {http://lib.ugent.be/fulltxt/RUG01/001/356/450/RUG01-001356450\_2010\_0001\_AC.pdf},
  year         = {2009},
}

Chicago
Raemdonck, Koen. 2009. “Biodegradable Dextran Nanogels as Functional Carriers for the Intracellular Delivery of Small Interfering RNA”. Ghent, Belgium: Ghent University. Faculty of Pharmaceutical Sciences.
APA
Raemdonck, K. (2009). Biodegradable dextran nanogels as functional carriers for the intracellular delivery of small interfering RNA. Ghent University. Faculty of Pharmaceutical Sciences, Ghent, Belgium.
Vancouver
1.
Raemdonck K. Biodegradable dextran nanogels as functional carriers for the intracellular delivery of small interfering RNA. [Ghent, Belgium]: Ghent University. Faculty of Pharmaceutical Sciences; 2009.
MLA
Raemdonck, Koen. “Biodegradable Dextran Nanogels as Functional Carriers for the Intracellular Delivery of Small Interfering RNA.” 2009 : n. pag. Print.