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Self-assembling Modified β‑Cyclodextrin Nanoparticles as Neuronal siRNA Delivery Vectors: Focus on Huntington’s Disease

Overview of attention for article published in Molecular Pharmaceutics, January 2013
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Title
Self-assembling Modified β‑Cyclodextrin Nanoparticles as Neuronal siRNA Delivery Vectors: Focus on Huntington’s Disease
Published in
Molecular Pharmaceutics, January 2013
DOI 10.1021/mp3003946
Pubmed ID
Authors

Bruno M. D. C. Godinho, Julien R. Ogier, Raphael Darcy, Caitriona M. O’Driscoll, John F. Cryan

Abstract

Huntington's disease (HD) is a rare autosomal dominant neurodegenerative disease caused by the expression of a toxic Huntingtin (HTT) protein. The use of short interfering RNAs (siRNAs) to silence the mutant protein is one of the most promising therapeutic strategies under investigation. The biggest caveat to siRNA-based approaches is the lack of efficient and nontoxic delivery vectors for siRNA delivery to the central nervous system. In this study, we investigated the potential of modified amphiphilic β-cyclodextrins (CDs), oligosaccharide-based molecules, as novel siRNA neuronal carriers. We show that CDs formed nanosize particles which were stable in artificial cerebrospinal fluid. Moreover, these complexes were able to reduce the expression of the HTT gene in rat striatal cells (ST14A-HTT120Q) and in human HD primary fibroblasts. Only limited toxicity was observed with CD·siRNA nanoparticles in any of the in vitro models used. Sustained knockdown effects were observed in the striatum of the R6/2 mouse model of HD after single direct injections of CD·siRNA nanoparticles. Repeated brain injections of CD·siRNA complexes resulted in selective alleviation of motor deficits in this mouse model. Together these data support the utility of modified β-CDs as efficient and safe siRNA delivery vectors for RNAi-based therapies for neuropsychiatric and neurodegenerative disorders.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 107 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 2 2%
Ireland 2 2%
Germany 1 <1%
Unknown 102 95%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 25 23%
Researcher 14 13%
Student > Bachelor 11 10%
Student > Doctoral Student 9 8%
Student > Master 8 7%
Other 19 18%
Unknown 21 20%
Readers by discipline Count As %
Agricultural and Biological Sciences 22 21%
Pharmacology, Toxicology and Pharmaceutical Science 15 14%
Chemistry 13 12%
Medicine and Dentistry 9 8%
Engineering 7 7%
Other 20 19%
Unknown 21 20%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 August 2015.
All research outputs
#13,375,146
of 22,691,736 outputs
Outputs from Molecular Pharmaceutics
#1,818
of 4,069 outputs
Outputs of similar age
#159,216
of 282,271 outputs
Outputs of similar age from Molecular Pharmaceutics
#42
of 69 outputs
Altmetric has tracked 22,691,736 research outputs across all sources so far. This one is in the 39th percentile – i.e., 39% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,069 research outputs from this source. They receive a mean Attention Score of 4.6. This one has gotten more attention than average, scoring higher than 54% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 282,271 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 42nd percentile – i.e., 42% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 69 others from the same source and published within six weeks on either side of this one. This one is in the 39th percentile – i.e., 39% of its contemporaries scored the same or lower than it.