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Click-Modified Cyclodextrins as Nonviral Vectors for Neuronal siRNA Delivery
- Source :
- ACS Chemical Neuroscience. 3:744-752
- Publication Year :
- 2012
- Publisher :
- American Chemical Society (ACS), 2012.
-
Abstract
- 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 β-cyclodextrin (CD) vector was synthesised, which complexed siRNA to form cationic nanoparticles of less than 200nm in size. Furthermore, it conferred stability in serum to the siRNA cargo. The in vitro performance of the CD in both immortalised hypothalamic neurons and primary hippocampal neurons was evaluated. The CD facilitated high levels of intracellular delivery of labelled siRNA, whilst 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.
- Subjects :
- Physiology
Cognitive Neuroscience
Genetic Vectors
Gene delivery
Biochemistry
Rats, Sprague-Dawley
RNA interference
Nanotechnology
Animals
Luciferase
Viability assay
Vector (molecular biology)
RNA, Small Interfering
Cells, Cultured
Glyceraldehyde 3-phosphate dehydrogenase
Neurons
Cyclodextrins
Gene knockdown
biology
Click chemistry
Oligonucleotide
Gene Transfer Techniques
Cell Biology
General Medicine
Molecular biology
Rats
Cell biology
siRNA
biology.protein
Click Chemistry
Subjects
Details
- ISSN :
- 19487193
- Volume :
- 3
- Database :
- OpenAIRE
- Journal :
- ACS Chemical Neuroscience
- Accession number :
- edsair.doi.dedup.....2da25a3edfc8cdeef4388fd0da8e681d