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Highly efficient small interfering RNA delivery to primary mammalian neurons induces MicroRNA-like effects before mRNA degradation

The study of protein function in neurons has been hindered by the lack of highly efficient, nontoxic methods of inducing RNA interference in such cells. Here we show that application of synthetic small interfering RNA (siRNA) linked to the vector peptide Penetratin1 results in rapid, highly efficien... Full description

Journal Title: The Journal of neuroscience : the official journal of the Society for Neuroscience 10 November 2004, Vol.24(45), pp.10040-6
Main Author: Davidson, Thomas J
Other Authors: Harel, Sivan , Arboleda, Valerie A , Prunell, Giselle F , Shelanski, Michael L , Greene, Lloyd A , Troy, Carol M
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1529-2401 ; PMID: 15537872 Version:1
Link: http://pubmed.gov/15537872
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recordid: medline15537872
title: Highly efficient small interfering RNA delivery to primary mammalian neurons induces MicroRNA-like effects before mRNA degradation
format: Article
creator:
  • Davidson, Thomas J
  • Harel, Sivan
  • Arboleda, Valerie A
  • Prunell, Giselle F
  • Shelanski, Michael L
  • Greene, Lloyd A
  • Troy, Carol M
subjects:
  • Gene Targeting -- Methods
  • Neurons -- Drug Effects
  • Protein Biosynthesis -- Drug Effects
  • RNA, Messenger -- Metabolism
  • RNA, Small Interfering -- Pharmacology
ispartof: The Journal of neuroscience : the official journal of the Society for Neuroscience, 10 November 2004, Vol.24(45), pp.10040-6
description: The study of protein function in neurons has been hindered by the lack of highly efficient, nontoxic methods of inducing RNA interference in such cells. Here we show that application of synthetic small interfering RNA (siRNA) linked to the vector peptide Penetratin1 results in rapid, highly efficient uptake of siRNA by entire populations of cultured primary mammalian hippocampal and sympathetic neurons. This treatment leads to specific knock-down of targeted proteins within hours without the toxicity associated with transfection. In contrast to current methods, our technique permits study of protein function across entire populations with minimal disturbance of complex cellular networks. Using this technique, we found that protein knock-down (evident after 6 hr) precedes any decrease in targeted message (evident after 24 hr), suggesting an early, translational repression by perfectly targeted siRNAs.
language: eng
source:
identifier: E-ISSN: 1529-2401 ; PMID: 15537872 Version:1
fulltext: fulltext
issn:
  • 15292401
  • 1529-2401
url: Link


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titleHighly efficient small interfering RNA delivery to primary mammalian neurons induces MicroRNA-like effects before mRNA degradation
creatorDavidson, Thomas J ; Harel, Sivan ; Arboleda, Valerie A ; Prunell, Giselle F ; Shelanski, Michael L ; Greene, Lloyd A ; Troy, Carol M
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subjectGene Targeting -- Methods ; Neurons -- Drug Effects ; Protein Biosynthesis -- Drug Effects ; RNA, Messenger -- Metabolism ; RNA, Small Interfering -- Pharmacology
descriptionThe study of protein function in neurons has been hindered by the lack of highly efficient, nontoxic methods of inducing RNA interference in such cells. Here we show that application of synthetic small interfering RNA (siRNA) linked to the vector peptide Penetratin1 results in rapid, highly efficient uptake of siRNA by entire populations of cultured primary mammalian hippocampal and sympathetic neurons. This treatment leads to specific knock-down of targeted proteins within hours without the toxicity associated with transfection. In contrast to current methods, our technique permits study of protein function across entire populations with minimal disturbance of complex cellular networks. Using this technique, we found that protein knock-down (evident after 6 hr) precedes any decrease in targeted message (evident after 24 hr), suggesting an early, translational repression by perfectly targeted siRNAs.
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titleHighly efficient small interfering RNA delivery to primary mammalian neurons induces MicroRNA-like effects before mRNA degradation
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abstractThe study of protein function in neurons has been hindered by the lack of highly efficient, nontoxic methods of inducing RNA interference in such cells. Here we show that application of synthetic small interfering RNA (siRNA) linked to the vector peptide Penetratin1 results in rapid, highly efficient uptake of siRNA by entire populations of cultured primary mammalian hippocampal and sympathetic neurons. This treatment leads to specific knock-down of targeted proteins within hours without the toxicity associated with transfection. In contrast to current methods, our technique permits study of protein function across entire populations with minimal disturbance of complex cellular networks. Using this technique, we found that protein knock-down (evident after 6 hr) precedes any decrease in targeted message (evident after 24 hr), suggesting an early, translational repression by perfectly targeted siRNAs.
pmid15537872
doi10.1523/JNEUROSCI.3643-04.2004
date2004-11-10