FolamiRs : Ligand-targeted, vehicle-free delivery of microRNAs for the treatment of cancer
Menée notamment sur des lignées cellulaires de cancer du sein triplement négatif et sur un modèle de cancer du poumon, cette étude met en évidence l'intérêt de FolamiR, un conjugué microARN-folate ne nécessitant pas l'utilisation de stratégies de protection, pour traiter les cellules cancéreuses surexprimant le récepteur des folates
MicroRNAs (miRNAs), small noncoding nucleotides that regulate gene expression, are attractive therapeutic targets for cancer. The rapid degradation of miRNA mimics in vivo has spurred the use of protection strategies such as liposomes and backbone modification; however, this can hinder miRNA stability, activity, and uptake efficiency. Here, Orellana et al. showed that vehicle-free miRNA could be targeted to cancer cells that overexpress the folate receptor. MiR-34a that was attached to folate, the ligand of the folate receptor, increased miR-34a copy number and reduced tumor size when delivered to mice with lung and breast cancer tumors. Folate-siRNA could also be delivered, suggesting that this conjugation approach for targeted delivery may be compatible with other small RNAs.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.