Title |
Selective targeting of point-mutated KRAS through artificial microRNAs
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Published in |
Proceedings of the National Academy of Sciences of the United States of America, May 2017
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DOI | 10.1073/pnas.1620562114 |
Pubmed ID | |
Authors |
Mario Acunzo, Giulia Romano, Giovanni Nigita, Dario Veneziano, Luigi Fattore, Alessandro Laganà, Nicola Zanesi, Paolo Fadda, Matteo Fassan, Lara Rizzotto, Raleigh Kladney, Vincenzo Coppola, Carlo M Croce |
Abstract |
Mutated protein-coding genes drive the molecular pathogenesis of many diseases, including cancer. Specifically, mutated KRAS is a documented driver for malignant transformation, occurring early during the pathogenesis of cancers such as lung and pancreatic adenocarcinomas. Therapeutically, the indiscriminate targeting of wild-type and point-mutated transcripts represents an important limitation. Here, we leveraged on the design of miRNA-like artificial molecules (amiRNAs) to specifically target point-mutated genes, such as KRAS, without affecting their wild-type counterparts. Compared with an siRNA-like approach, the requirement of perfect complementarity of the microRNA seed region to a given target sequence in the microRNA/target model has proven to be a more efficient strategy, accomplishing the selective targeting of point-mutated KRAS in vitro and in vivo. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 5 | 36% |
China | 1 | 7% |
Norway | 1 | 7% |
Unknown | 7 | 50% |
Demographic breakdown
Type | Count | As % |
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Scientists | 8 | 57% |
Members of the public | 6 | 43% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 77 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 18 | 23% |
Student > Ph. D. Student | 13 | 17% |
Student > Bachelor | 7 | 9% |
Other | 6 | 8% |
Professor | 4 | 5% |
Other | 10 | 13% |
Unknown | 19 | 25% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 22 | 29% |
Medicine and Dentistry | 14 | 18% |
Agricultural and Biological Sciences | 5 | 6% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 4% |
Chemistry | 3 | 4% |
Other | 9 | 12% |
Unknown | 21 | 27% |