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Deprecated: Implicit conversion from float 300.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Pharm+Res 2009 ; 26 (5): 1181-91 Nephropedia Template TP
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Highly efficient transfection of rat cortical neurons using carbosilane dendrimers unveils a neuroprotective role for HIF-1alpha in early chemical hypoxia-mediated neurotoxicity #MMPMID19191011
Posadas I; Lopez-Hernandez B; Clemente MI; Jimenez JL; Ortega P; de la Mata J; Gomez R; Munoz-Fernandez MA; Cena V
Pharm Res 2009[May]; 26 (5): 1181-91 PMID19191011show ga
PURPOSE: 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-1alpha (HIF1-alpha) during chemical hypoxia-mediated neurotoxicity. METHODS: Chemical hypoxia was induced in primary rat cortical neurons by exposure to CoCl(2). 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. RESULTS: 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. CONCLUSION: 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.