TY  - JOUR
  - O'Mahony, AM,Godinho, BMDC,Ogier, J,Devocelle, M,Darcy, R,Cryan, JF,O'Driscoll, CM
  - 2012
  - January
  - ACS Chemical Neuroscience
  - Click-Modified Cyclodextrins as Nonviral Vectors for Neuronal siRNA Delivery
  - Published
  - ()
  - Nanotechnology cyclodextrins click chemistry siRNA delivery neurons gene knockdown SMALL INTERFERING RNA ADIPOKINE GENE-EXPRESSION BETA-CYCLODEXTRIN MAMMALIAN NEURONS STRUCTURAL MODIFICATIONS NERVOUS-SYSTEM PLASMID DNA CELLS TRANSFECTION NANOPARTICLES
  - 3
  - 744
  - 752
  - RNA interference (RNAi) holds great promise as a strategy to further our understanding of gene function in the central nervous system (CNS) and as a therapeutic approach for neurological and neurodegenerative diseases. However, the potential for its use is hampered by the lack of siRNA delivery vectors which are both safe and highly efficient. Cyclodextrins have been shown to be efficient and low toxicity gene delivery vectors in various cell types in vitro. However, to date, they have not been exploited for delivery of oligonucleotides to neurons. To this end, a modified beta-cyclodextrin (CD) vector was synthesized, which complexed siRNA to form cationic nanoparticles of less than 200 nm in size. Furthermore, it conferred stability in serum to the siRNA cargo. The in vitro performance of the CD in both immortalized hypothalamic neurons and primary hippocampal neurons was evaluated. The CD facilitated high levels of intracellular delivery of labeled siRNA, while maintaining at least 80% cell viability. Significant gene knockdown was achieved, with a reduction in luciferase expression of up to 68% and a reduction in endogenous glyceraldehyde phosphate dehydrogenase (GAPDH) expression of up to 40%. To our knowledge, this is the first time that a modified CD has been used as a safe and efficacious vector for siRNA delivery into neuronal cells.
  - DOI 10.1021/cn3000372
DA  - 2012/01
ER  - 

@article{V190495869,
   = {O'Mahony,  AM and Godinho,  BMDC and Ogier,  J and Devocelle,  M and Darcy,  R and Cryan,  JF and O'Driscoll,  CM },
   = {2012},
   = {January},
   = {ACS Chemical Neuroscience},
   = {Click-Modified Cyclodextrins as Nonviral Vectors for Neuronal siRNA Delivery},
   = {Published},
   = {()},
   = {Nanotechnology cyclodextrins click chemistry siRNA delivery neurons gene knockdown SMALL INTERFERING RNA ADIPOKINE GENE-EXPRESSION BETA-CYCLODEXTRIN MAMMALIAN NEURONS STRUCTURAL MODIFICATIONS NERVOUS-SYSTEM PLASMID DNA CELLS TRANSFECTION NANOPARTICLES},
   = {3},
  pages = {744--752},
   = {{RNA interference (RNAi) holds great promise as a strategy to further our understanding of gene function in the central nervous system (CNS) and as a therapeutic approach for neurological and neurodegenerative diseases. However, the potential for its use is hampered by the lack of siRNA delivery vectors which are both safe and highly efficient. Cyclodextrins have been shown to be efficient and low toxicity gene delivery vectors in various cell types in vitro. However, to date, they have not been exploited for delivery of oligonucleotides to neurons. To this end, a modified beta-cyclodextrin (CD) vector was synthesized, which complexed siRNA to form cationic nanoparticles of less than 200 nm in size. Furthermore, it conferred stability in serum to the siRNA cargo. The in vitro performance of the CD in both immortalized hypothalamic neurons and primary hippocampal neurons was evaluated. The CD facilitated high levels of intracellular delivery of labeled siRNA, while maintaining at least 80% cell viability. Significant gene knockdown was achieved, with a reduction in luciferase expression of up to 68% and a reduction in endogenous glyceraldehyde phosphate dehydrogenase (GAPDH) expression of up to 40%. To our knowledge, this is the first time that a modified CD has been used as a safe and efficacious vector for siRNA delivery into neuronal cells.}},
   = {DOI 10.1021/cn3000372},
  source = {IRIS}
}