microRNA Replacement Therapy
Mirna’s microRNA Technology

Preclinical studies have shown that mimics of naturally occurring microRNAs can reduce the proliferation of cultured cancer cells, cause significant tumor regression in mouse models and reduce the tumor-forming capacity of cancer stem cells. We believe controlling these multiple cancer pathways may also reduce the risk of the development of drug resistance, one of the more prevalent problems of modern cancer therapies.

miRNA Replacement Therapy
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Many of today’s cancer treatments were designed to target only one or two oncogenes or pathways. In contrast, microRNA therapy is designed to inhibit multiple oncogenic pathways, which we believe may be a more effective approach to treat complex, multi-factorial diseases, such as cancer.

Mirna has identified several tumor suppressor microRNAs that we believe play key roles in preventing normal cells from becoming cancerous; these microRNAs are reduced or lost in virtually all cancers and to varying degrees also in cancer stem cells.

Mirna’s approach to creating microRNA therapeutics builds on the following proprietary technologies and capabilities:
  • microRNA Pipeline: The selection of microRNA targets for therapeutic development has been guided by more than a decade of experience of our scientists in the research and discovery of the expression, function and therapeutic application of microRNAs. We consider ideal therapeutic candidates to be those that have strong evidence for application in human disease and are most effective in preclinical in vitro and in vivo animal studies.
  • Chemistry: Mirna has developed a series of proprietary double-stranded microRNA molecules that include a mimic of the natural microRNA sequence. The active strand of the mimic contains a sequence identical to the microRNA that is normally expressed in the target cell. The second, passenger strand is modified to facilitate proper loading of the active strand into the protein complex necessary for microRNA function.
  • Drug Delivery: Due to recent advances in delivery technologies for RNA-based therapeutics, Mirna established proprietary model systems and analytical methods to assess and develop these drug delivery technologies. Mirna continues to evaluate delivery technologies to target a broader group of tissues and tumor types.
Mirna has an exclusive license from Marina Biotech, Inc. to the patent estate covering the SMARTICLES® liposomal delivery technology for several of our lead microRNA product candidates, including miR-34, let-7 and three other targets. The SMARTICLES formulation offers key efficacy and safety benefits, including the ability to deliver high numbers of microRNA mimic molecules to both healthy and cancerous cells, including tumor cells located in the liver, lymph nodes (melanoma metastasis), lung and colon, as well as to highly vascularized tissues, such as adrenal gland and kidney, and also to bone marrow. Mirna continues to evaluate alternative delivery technologies to target additional tissues and tumor types.

Mirna continues to welcome collaborative inquiries related to the in vivo delivery of oligonucleotides. Please contact busdev@mirnarx.com.

Therapeutic Advantages

microRNA tumor suppressor mimics represent a potential first-in-class cancer therapy:
  • microRNAs can function as natural tumor suppressors, acting as endogenous regulators of cancer, including tumor growth, cancer stem cells and metastasis
  • microRNAs control multiple pathways, presenting the prospect of one microRNA mimic regulating numerous oncogenes across multiple cancer pathways, as well as tumor immune evasion pathways
  • microRNAs are abundantly present in most normal human cells

miRNAs Multiple Pathways
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Tumor suppressor microRNAs inhibit the expression of multiple oncogenes, whether they function within the same or across multiple pathways. As a result, tumor suppressor microRNAs can inhibit a variety of cancer processes and have the potential to inhibit a broad range of cancer types. For example, miR-34 has been shown to regulate more than 30 oncogenes, including many that are the target of FDA-approved and investigational cancer drugs, as well as the immune-oncology checkpoint molecule PD-L1.

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