Antisense oligonucleotides for MYC-targeted cancer therapy
This technology identifies steric-blocking antisense oligonucleotides (ASOs) that target an indispensable noncoding region of MYC mRNA for the treatment of MYC-dependent cancers.
Unmet Need: Inhibitor for the treatment of MYC-driven cancers
MYC is dysregulated in approximately 70% of human cancers. Although MYC is a promising target for cancer therapy because of its central role in tumor initiation, progression, and maintenance across a wide range of cancer types, there are currently no FDA-approved direct MYC inhibitors on the market. Therapeutic targeting of MYC protein has remained challenging due to its intrinsically disordered structure that lacks well-defined druggable domains, and nuclear localization which creates a barrier for effective drug delivery.
The Technology: Steric-blocking antisense oligonucleotides targeting the MYC 3’ untranslated region
This technology is a set of steric-blocking antisense oligonucleotides (ASOs) that bind to a critical region within the 3’ untranslated region (3’UTR) of MYC mRNA. These ASOs bind and block cytoplasmic MYC mRNA function without inducing its degradation. Targeting this regulatory element disrupts MYC mRNA localization and impairs nuclear import of MYC protein, thereby suppressing MYC-dependent transcriptional activity. As a result, these ASOs can inhibit cancer cell growth without detectable toxicity.
This technology has been validated in human cancer cell lines, mouse models, and patient-derived tumor organoids.
Imetelstat, an FDA-approved oligonucleotide telomerase inhibitor for lower-risk myelodysplastic syndromes, provides clinical precedent for the feasibility of oligonucleotide-based therapeutics in cancer.
Applications:
- Treatment of multiple types of MYC-driven cancers
- Potential therapeutic application in other MYC-driven diseases
- Potential use in combination therapy approaches
- Research tool for analyzing the role of MYC in aging
- Research tool for analyzing the role of MYC in metabolic disorders
- Research tool for analyzing the role of MYC in physiology
Advantages:
- Cytoplasmic targeting of a noncoding regulatory element in MYC mRNA
- Suppression of MYC activity without degradation of MYC mRNA or MYC protein
- Cancer cell growth inhibition across in vitro, in vivo, and in patient-derived organoids (PDOs)
- 2’-MOE steric-blocking ASOs design to minimize cleavage-based off-target effects and dsRNA-induced immunotoxicity
- No detectable toxicity in tested human cell lines
Lead Inventor:
Patent Information:
Patent Pending
Related Publications:
Tech Ventures Reference:
IR CU25384
Licensing Contact: Joan Martinez