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What if…

A Fundamental Observation Becomes a Key Discovery?

Cancer’s Resistance is Enabled by Epigenetic Regulation.

In response to treatment (chemotherapy and/or radiation), cancer cells change their transcriptional patterns to better survive stress-induced toxicity. The Polycomb Repressor Complex (PRC), a multiprotein complex that allows cancer cells to evade therapy, is normally kept in check by groups of functionally connected microRNAs. But in tumor cells under stress, these microRNAs are diminished or lost.

Many Cancers Evidence this “Epigenetic Plasticity,” Reducing or Eliminating the Effect of Current Therapies.

Ternalys Developed the SAGUARO Platform to Enable Simultaneous Delivery and Expression of Multiple microRNAs.​

The SAGUARO RNA platform is a novel, simple and effective method to cluster multiple, naturally occurring microRNAs of interest into transgenes that easily recapitulate microRNA networking in cells.

 

The SAGUARO “Engineered Chassis” blocks expression of multiple targeted messenger RNAs.

  • Applicable to broad range of intractable cancers and non-oncologic targets.
  • Synergistic with and enabling of other existing and experimental therapies.
  • Cluster scaffold can be designed with different RNA pieces to retain additional desired functions after cleavage.
Consensus shape for cleavage

LOOP: Consensus shape for cleavage
STEM: Biologically active component of the miRNA

Cell machinery recognizes the hairpin

Cell machinery recognizes the hairpin shape, cuts and releases the miRNA

SAGUARO Artificial miRNA Cluster
Recognized by cell machinery based on characteristic hairpin shape

Allows for “Plug and Play” delivery of multiple miRNA mimetics, anti-Mirs, aptamers or other RNAs.

Ternalys’ lead candidate (TT-003) shows promising data in preclinical cancer models, with clear pathway to First-in-Human trials in glioblastoma via intratumoral delivery.