Systemic delivery of tumor suppressor microRNA mimics using a neutral lipid emulsion inhibits lung tumors in mice.

By Phong Trang, J. Wiggins, C. Daige, C. Cho, M. Omotola, D. Brown, J. Weidhaas, A. Bader, Frank J. Slack. Molecular Therapy, 2011

668 citations recorded by the source corpus.

MicroRNAs (miRNAs) are emerging as potential cancer therapeutics, but effective delivery mechanisms to tumor sites are a roadblock to utility. Here we show that systemically delivered, synthetic miRNA mimics in complex with a novel neutral lipid emulsion are preferentially targeted to lung tumors and show therapeutic benefit in mouse models of lung cancer. Therapeutic delivery was demonstrated using mimics of the tumor suppressors, microRNA-34a (miR-34a) and let-7, both of which are often down regulated or lost in lung cancer. Systemic treatment of a Kras-activated autochthonous mouse model of non-small cell lung cancer (NSCLC) led to a significant decrease in tumor burden. Specifically, mice treated with miR-34a displayed a 60% reduction in tumor area compared to mice treated with a miRNA control. Similar results were obtained with the let-7 mimic. These findings provide direct evidence that synthetic miRNA mimics can be systemically delivered to the mammalian lung and support the promise of miRNAs as a future targeted therapy for lung cancer.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/be830b1c3e4a66bd1bcd15ea1c41d3496f9e24e1

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Citations in the corpus

MicroRNAs in stress signaling and human disease (2012, background): “Using this approach, systemic delivery of miRNA mimics has been successfully applied in multiple experimental tumor models in mice, resulting in tumor suppression without apparent toxicity in normal tissues (Pramanik et al., 2011; Trang et al., 2011).”
In vivo delivery of miRNAs for cancer therapy: Challenges and strategies (2014, methodology): “later demonstrated that systemic delivery of miR-34a or let-7 miRNA mimics in the neutral lipid-based formulation showed a 60% reduction of tumor burden in a K-ras-activated autochthonous mouse model of NSCLC compared with a control miRNA [137].”
miR-34 – a microRNA replacement therapy is headed to the clinic (2012, background): “…et al., 2010). www.frontiersin.org July 2012 | Volume 3 | Article 120 | 5 “fgene-03-00120” — 2012/6/29 — 15:59 — page 6 — #6 Similar results were obtained in a genetically engineered mouse model of lung cancer that is based on the constitutively active KRAS mutant G12D (Trang et al., 2011).”
Development of microRNA therapeutics is coming of age (2014, positive): “Moreover, administration of such lipid-based miRNA mimic formulations did not elicit an immune response and showed no increase in kidney or liver enzymes, suggesting that this strategy is well tolerated in vivo (Trang et al , 2011).”
MicroRNA and cancer (2012, background): “Lastly, redundancy also exists at the level of the target mRNAs where different miRNAswith distinct seed sequencesmay corepress the same target (Tsang et al., 2010).”