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.
Original language | English |
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Pages (from-to) | E4203-E4212 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 114 |
Issue number | 21 |
DOIs | |
State | Published - 23 May 2017 |
Keywords
- Artificial microRNA
- KRAS
- RNAi