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Native chemical ligation for conversion of sequence-defined oligomers into targeted pDNA and siRNA carriers

Overview of attention for article published in Journal of Controlled Release, February 2014
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Title
Native chemical ligation for conversion of sequence-defined oligomers into targeted pDNA and siRNA carriers
Published in
Journal of Controlled Release, February 2014
DOI 10.1016/j.jconrel.2014.02.015
Pubmed ID
Authors

Can Yang Zhang, Petra Kos, Katharina Müller, Waldemar Schrimpf, Christina Troiber, Ulrich Lächelt, Claudia Scholz, Don C. Lamb, Ernst Wagner

Abstract

Native chemical ligation (NCL) was established for the conversion of sequence-defined oligomers of different topologies into targeted and PEG shielded pDNA and siRNA carriers. From an existing library of non-targeted oligoethanamino amides, six oligomers containing N-terminal cysteines were selected as cationic cores, to which monodisperse polyethylene glycol (PEG) containing terminal folic acid as targeting ligand (or terminal alanine as targeting negative control ligand) were attached by NCL. Ligated conjugates plus controls (in sum 18 oligomers) were evaluated for pDNA or siRNA gene delivery. Biophysical characteristics including nucleic acid binding in the absence or presence of serum, as well as biological activities in cellular uptake and gene transfer (or gene silencing, respectively) were determined. In most cases, the folic acid-PEG-ligated oligomers displayed a strongly improved cellular binding, uptake and gene transfer into receptor-positive KB cells as compared to the alanine-PEG controls. Changing the topological structures by increasing the number of cationic arms, adding tyrosine trimers as polyplex stabilizing domains, or histidines facilitating endosomal escape resulted in beneficial gene transfer characteristics. The screen revealed different requirements for pDNA and siRNA delivery. A folate-PEG ligated histidinylated four-arm oligomer was most effective for pDNA delivery but inactive for siRNA, whereas a folate-PEG-ligated three-arm oligomer with tyrosine trimer modifications was most effective in siRNA mediated gene silencing. The results demonstrate the site-selective NCL reaction as powerful method to modify existing oligomers. Thus multifunctional targeted carriers can be obtained with ease and used to identify lead structures for subsequent in vivo delivery.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 23 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
India 1 4%
Unknown 22 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 4 17%
Researcher 4 17%
Student > Doctoral Student 3 13%
Professor 3 13%
Student > Master 3 13%
Other 4 17%
Unknown 2 9%
Readers by discipline Count As %
Chemistry 9 39%
Agricultural and Biological Sciences 3 13%
Pharmacology, Toxicology and Pharmaceutical Science 2 9%
Biochemistry, Genetics and Molecular Biology 2 9%
Engineering 2 9%
Other 2 9%
Unknown 3 13%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 01 March 2014.
All research outputs
#17,286,379
of 25,374,647 outputs
Outputs from Journal of Controlled Release
#7,541
of 9,727 outputs
Outputs of similar age
#146,231
of 239,851 outputs
Outputs of similar age from Journal of Controlled Release
#54
of 81 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 9,727 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.9. This one is in the 20th percentile – i.e., 20% of its peers scored the same or lower than it.
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We're also able to compare this research output to 81 others from the same source and published within six weeks on either side of this one. This one is in the 23rd percentile – i.e., 23% of its contemporaries scored the same or lower than it.