TY - JOUR
T1 - Selective targeting of point-mutated KRAS through artificial microRNAs
AU - Acunzo, Mario
AU - Romano, Giulia
AU - Nigita, Giovanni
AU - Veneziano, Dario
AU - Fattore, Luigi
AU - Laganà, Alessandro
AU - Zanesi, Nicola
AU - Fadda, Paolo
AU - Fassan, Matteo
AU - Rizzotto, Lara
AU - Kladney, Raleigh
AU - Coppola, Vincenzo
AU - Croce, Carlo M.
PY - 2017/5/23
Y1 - 2017/5/23
N2 - 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.
AB - 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.
KW - Artificial microRNA
KW - KRAS
KW - RNAi
UR - http://www.scopus.com/inward/record.url?scp=85019631500&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85019631500&partnerID=8YFLogxK
U2 - 10.1073/pnas.1620562114
DO - 10.1073/pnas.1620562114
M3 - Article
AN - SCOPUS:85019631500
VL - 114
SP - E4203-E4212
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 21
ER -