InteRNA’s platform provides competitive edge in target selection

InteRNA Technologies created the core of its technology platform using massively parallel sequencing and proprietary, highly advanced bioinformatics methods to analyze, predict, and validate miRNA sequences. This has led to the identification of a large number of novel miRNAs. InteRNA further analyzed an extensive collection of small RNAs from different human tissues to refine existing annotations and establish miRNA expression patterns. Comparison of miRNA cloning frequencies in the different tissues allowed for identification of miRNA sets predominantly expressed in specific tissues, as well as arm-switching events and differential isomiR expression.

Our approach


  • Berezikov, E., van Tetering, G., Verheul, M., van de Belt, J., van Laake, L., Vos, J., Verloop, R., van de Wetering, M., Guryev, V., Takada, S., van Zonneveld, A. J., Mano, H., Plasterk, R. and Cuppen, E. (2006). Many novel mammalian microRNA candidates identified by extensive cloning and RAKE analysis.  Genome Res., 2006, 16: 1289-1298
  • Berezikov, E., Thuemmler, F., van Laake, L., Kondova, I., Bontrop, R., Cuppen, E. and Plasterk, R. H. (2006). Diversity of microRNAs in human and chimpanzee brain. Nat. Genet., 2006, 38: 1375-1377
  • Takada, S., Berezikov, E., Yamashita, Y., Lagos-Quintana, M., Kloosterman, W. P., Enomoto, M., Hatanaka, H., Fujiwara, S., Watanabe, H., Soda, M., Choi, Y. L., Plasterk, R. H. A., Cuppen, E. and Mano, H. (2006). Mouse microRNA profiles determined with a new and sensitive cloning method. Nucleic Acids Res., 2006, 34:e115
  • Berezikov, E., Guryev, V., van de Belt, J., Wienholds, E., Plasterk, R. H. and Cuppen, E. (2005). Phylogenetic shadowing and computational identification of human microRNA genes Cell, 2005, 120: 21-24

InteRNA’s technology platform consists of

  • Lentiviral-based miRNA overexpression library
    Enabling high-throughput functional genomics cell-based assay screening to systematically address the biological function of miRNAs, we constructed and validated a lentiviral miRNA expression library containing annotated and candidate human miRNA precursors. We demonstrated its functionality to identify miRNA drug candidates in both short- and long-term assays with focus on interference in cancer pathways, cell proliferation and death (apoptosis), epithelial-to-mesenchymal transition, invasion and migration, anchorage-independent cell growth, and angiogenesis in our Oncology programs and on neurite outgrowth and neuronal migration in our CNS programs.
  • Identification mode of action & biomarkers
    InteRNA’s platform to identify the mRNAs regulated by the miRNA therapeutic drug candidates comprises RISC immunoprecipitation and RNAseq analysis of cells upon miRNA overexpression (identifying downregulated mRNAs). We correlate these datasets with those generated by target prediction and pathway analysis software tools and literature. Identified downstream-regulated mRNAs are subsequently confirmed by 3′-UTR assays, qPCR, ISH/IHC, and Western blotting.

    The regulated mRNAs can serve as biomarkers for further clinical development of the therapeutic miRNA drug candidates.

  • Enabling next-generation drug delivery technology
    In our oncology programs, InteRNA’s drug delivery technology for miRNA mimics is based on a 3rd-generation LNP, incl. tissue-specific lipid linkers for improved distribution and uptake thereby addressing key criteria as distribution to cell of interest, cellular uptake, endosomal escape, and prevention of on-target toxicity and off-target effects.