PVT1 Micropeptide Compositions for Selective Myc Suppression
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Solution Overview
Problem
Current cancer therapies lack effective ways to target Myc, a proto-oncogene overexpressed in many human cancers, which plays a crucial role in neoplastic cell growth and proliferation.
Innovation Solution
Development of synthetic nucleic acid sequences encoding Plasmacytoma variant translocation 1_217 (PVT1_217) splice variant micropeptides, which can be administered to inhibit Myc expression by targeting the PVT1 locus, and their use in pharmaceutical compositions with cancer cell targeting moieties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current cancer therapies are used, then general cancer treatment is provided, but effective targeting of Myc proto-oncogene is not achieved
Solution Approach 1:
The patent uses PVT1 micropeptides as intermediary molecules that specifically bind to Myc proto-oncogene products. These micropeptides act as mediators between the therapeutic agent and the Myc target, enabling selective inhibition of Myc-driven cancer pathways while sparing normal cellular functions. The PVT1 micropeptide sequence is designed to interact with Myc's transactivation domain, blocking its oncogenic activity specifically in Myc-overexpressing cancers.
Solution Approach 2:
The invention applies local quality by designing cancer cell targeting moieties that are specifically activated or bound only in the presence of Myc-overexpressing cancer cells. The therapeutic composition delivers PVT1 micropeptides selectively to tumors with high Myc expression, ensuring that the inhibitory effect is localized to the pathological tissue rather than affecting healthy cells systemically.
2Quantity of substance
If synthetic nucleic acid sequences encoding PVT1 micropeptides are administered, then Myc levels are reduced in cancer cells, but delivery specificity to cancer cells must be ensured
Solution Approach 1:
The patent employs multifunctional therapeutic compositions that combine PVT1 micropeptide encoding nucleic acids with cancer cell targeting moieties and delivery vehicles. This multi-functional approach enables a single composition to perform multiple functions: protecting the nucleic acid from degradation, delivering it specifically to cancer cells, and enabling translation of the micropeptide only within the target cells. The targeting moiety may include antibodies, peptides, or ligands that recognize cancer-specific surface markers.
Solution Approach 2:
The cancer cell targeting moiety acts as an intermediary that bridges the synthetic nucleic acid and the cancer cell surface. This mediator ensures that the therapeutic payload is delivered exclusively to Myc-driven cancer cells through specific binding interactions, preventing off-target effects in healthy tissues while maintaining high levels of Myc suppression in the tumor.
3Productivity
If PVT1 micropeptides are used to inhibit Myc expression, then cell division is inhibited, but effective delivery and expression mechanisms are required
Solution Approach 1:
The patent utilizes parameter changes in the form of modified nucleic acid sequences that enhance stability, translation efficiency, and cellular uptake. The synthetic nucleic acid encoding PVT1 micropeptide incorporates optimized codon usage, stabilizing modifications, and structural elements that maximize protein expression levels within cancer cells. These parameter optimizations ensure sufficient micropeptide production to achieve therapeutic Myc suppression without requiring excessively complex delivery infrastructure.
Data Source
AI summary
Described herein are methods and compositions for diagnosing, treating, or ameliorating symptoms of cancer, including MYC-driven and KRAS-driven cancer, with therapeutic HNB polypeptides. In some embodiments, disclosed herein are compositions comprising a synthetic nucleic acid sequence encoding a Plasmacytoma variant translocation 1_217 (PVT1_217) splice variant micropeptide, wherein the PVT1_217 splice variant micropeptide comprises at least 10 contiguous amino acids that are identical to a peptide encoded by a short open reading frame (shORF) located at the junction of Exon 3 and Exon 4 of human PVT 1_217.