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Mendeley readers
Attention Score in Context
| Title |
2′-OMe-phosphorodithioate-modified siRNAs show increased loading into the RISC complex and enhanced anti-tumour activity
|
|---|---|
| Published in |
Nature Communications, March 2014
|
| DOI | 10.1038/ncomms4459 |
| Pubmed ID | |
| Authors |
Sherry Y. Wu, Xianbin Yang, Kshipra M. Gharpure, Hiroto Hatakeyama, Martin Egli, Michael H. McGuire, Archana S. Nagaraja, Takahito M. Miyake, Rajesha Rupaimoole, Chad V. Pecot, Morgan Taylor, Sunila Pradeep, Malgorzata Sierant, Cristian Rodriguez-Aguayo, Hyun J. Choi, Rebecca A. Previs, Guillermo N. Armaiz-Pena, Li Huang, Carlos Martinez, Tom Hassell, Cristina Ivan, Vasudha Sehgal, Richa Singhania, Hee-Dong Han, Chang Su, Ji Hoon Kim, Heather J. Dalton, Chandra Kovvali, Khandan Keyomarsi, Nigel A. J. McMillan, Willem W. Overwijk, Jinsong Liu, Ju-Seog Lee, Keith A. Baggerly, Gabriel Lopez-Berestein, Prahlad T. Ram, Barbara Nawrot, Anil K. Sood |
| Abstract |
Improving small interfering RNA (siRNA) efficacy in target cell populations remains a challenge to its clinical implementation. Here, we report a chemical modification, consisting of phosphorodithioate (PS2) and 2'-O-Methyl (2'-OMe) MePS2 on one nucleotide that significantly enhances potency and resistance to degradation for various siRNAs. We find enhanced potency stems from an unforeseen increase in siRNA loading to the RNA-induced silencing complex, likely due to the unique interaction mediated by 2'-OMe and PS2. We demonstrate the therapeutic utility of MePS2 siRNAs in chemoresistant ovarian cancer mouse models via targeting GRAM domain containing 1B (GRAMD1B), a protein involved in chemoresistance. GRAMD1B silencing is achieved in tumours following MePS2-modified siRNA treatment, leading to a synergistic anti-tumour effect in combination with paclitaxel. Given the previously limited success in enhancing siRNA potency with chemically modified siRNAs, our findings represent an important advance in siRNA design with the potential for application in numerous cancer types. |
Mendeley readers
The data shown below were compiled from readership statistics for 125 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Japan | 3 | 2% |
| Germany | 1 | <1% |
| Austria | 1 | <1% |
| Unknown | 120 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 30 | 24% |
| Researcher | 23 | 18% |
| Student > Master | 13 | 10% |
| Student > Bachelor | 13 | 10% |
| Other | 8 | 6% |
| Other | 17 | 14% |
| Unknown | 21 | 17% |
| Readers by discipline | Count | As % |
|---|---|---|
| Chemistry | 28 | 22% |
| Biochemistry, Genetics and Molecular Biology | 23 | 18% |
| Agricultural and Biological Sciences | 23 | 18% |
| Pharmacology, Toxicology and Pharmaceutical Science | 8 | 6% |
| Medicine and Dentistry | 4 | 3% |
| Other | 14 | 11% |
| Unknown | 25 | 20% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. 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 June 2019.
All research outputs
#7,730,751
of 23,510,717 outputs
Outputs from Nature Communications
#38,359
of 48,849 outputs
Outputs of similar age
#74,535
of 222,576 outputs
Outputs of similar age from Nature Communications
#332
of 467 outputs
Altmetric has tracked 23,510,717 research outputs across all sources so far. This one is in the 44th percentile – i.e., 44% of other outputs scored the same or lower than it.
So far Altmetric has tracked 48,849 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 56.3. This one is in the 20th percentile – i.e., 20% of its peers scored the same or lower than it.
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 222,576 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 53% of its contemporaries.
We're also able to compare this research output to 467 others from the same source and published within six weeks on either side of this one. This one is in the 27th percentile – i.e., 27% of its contemporaries scored the same or lower than it.