期刊
PHARMACEUTICAL RESEARCH
卷 26, 期 5, 页码 1181-1191出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-009-9839-9
关键词
dendrimers; HIF1-alpha; Hypoxia; neurons; neurotoxicity
资金
- FIS [PI52112, PI081434]
- Ministerio de Sanidad y Consumo
- JCCM [PAI07-0063-7844, G02-019SAN03-23]
- Red Tematica de Investigacion Cooperativa Sanitaria ISCIII [RD06/0006/0035]
- FIPSE [36514/05, 36536/05, 24632/07]
- Ministerio de Educacion y Ciencia
- UCLM-CCM
- Red Tematica de Investigacion Cooperativa Sanitaria [RD06/0006/0035]
- [PI061479]
To study the effect of a non-viral vector (carbosilane dendrimer) to efficiently deliver small interfering RNA to postmitotic neurons to study the function of hypoxia-inducible factor-1 alpha (HIF1-alpha) during chemical hypoxia-mediated neurotoxicity. Chemical hypoxia was induced in primary rat cortical neurons by exposure to CoCl2. HIF1-alpha levels were determined by Western Blot and toxicity was evaluated by both MTT and LDH assays. Neurons were incubated with dendriplexes containing anti-HIF1-alpha siRNA and both uptake and HIF1-alpha knockdown efficiency were evaluated. We report that a non-viral vector (carbosilane dendrimer) can deliver specific siRNA to neurons and selectively block HIF1-alpha synthesis with similar efficiency to that achieved by viral vectors. Using this method, we have found that this transcription factor plays a neuroprotective role during the early phase of chemical hypoxia-mediated neurotoxicity. This work represents a proof-of-concept for the use of carbosilane dendrimers to deliver specific siRNA to postmitotic neurons to block selected protein synthesis. This indicates that this type of vector is a good alternative to viral vectors to achieve very high transfection levels in neurons. This also suggests that carbosilane dendrimers might be very useful for gene therapy.
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