TY - JOUR
T1 - FolamiRs
T2 - Ligand-targeted, vehicle-free delivery of microRNAs for the treatment of cancer
AU - Orellana, Esteban A.
AU - Tenneti, Srinivasarao
AU - Rangasamy, Loganathan
AU - Lyle, L. Tiffany
AU - Low, Philip S.
AU - Kasinski, Andrea L.
N1 - Funding Information:
This research was supported by a Pathway to Independence Grant (R00CA178091 to A.L.K.), the Purdue Center for Cancer Research (P30CA023168), the Indiana Clinical and Translational Sciences Institute (funded in part by grant #UL1 TR001108 from the NIH), National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (to A.L.K.), and Endocyte Grant (#200766 to P.S.L.).
Publisher Copyright:
Copyright © 2017 The Authors.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2017/8/2
Y1 - 2017/8/2
N2 - MicroRNAs are small RNAs that negatively regulate gene expression posttranscriptionally. Because changes in microRNA expression can promote or maintain disease states, microRNA-based therapeutics are being evaluated extensively. Unfortunately, the therapeutic potential of microRNA replacement is limited by deficient delivery vehicles. In this work, microRNAs are delivered in the absence of a protective vehicle. The method relies on direct attachment of microRNAs to folate (FolamiR), which mediates delivery of the conjugated microRNA into cells that overexpress the folate receptor. We show that the tumor-suppressive FolamiR, FolamiR-34a, is quickly taken up both by triple-negative breast cancer cells in vitro and in vivo and by tumors in an autochthonous model of lung cancer and slows their progression. This method delivers microRNAs directly to tumors in vivo without the use of toxic vehicles, representing an advance in the development of nontoxic, cancer-targeted therapeutics.
AB - MicroRNAs are small RNAs that negatively regulate gene expression posttranscriptionally. Because changes in microRNA expression can promote or maintain disease states, microRNA-based therapeutics are being evaluated extensively. Unfortunately, the therapeutic potential of microRNA replacement is limited by deficient delivery vehicles. In this work, microRNAs are delivered in the absence of a protective vehicle. The method relies on direct attachment of microRNAs to folate (FolamiR), which mediates delivery of the conjugated microRNA into cells that overexpress the folate receptor. We show that the tumor-suppressive FolamiR, FolamiR-34a, is quickly taken up both by triple-negative breast cancer cells in vitro and in vivo and by tumors in an autochthonous model of lung cancer and slows their progression. This method delivers microRNAs directly to tumors in vivo without the use of toxic vehicles, representing an advance in the development of nontoxic, cancer-targeted therapeutics.
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U2 - 10.1126/scitranslmed.aam9327
DO - 10.1126/scitranslmed.aam9327
M3 - Article
C2 - 28768807
AN - SCOPUS:85026673248
VL - 9
JO - Science translational medicine
JF - Science translational medicine
SN - 1946-6234
IS - 401
ER -