Biological Rationale
Cancer therapies have increasingly focused on targeting specific mutations or signaling pathway components that sustain tumor growth and survival signaling. These approaches can produce meaningful responses in select well defined patient populations. However, tumors frequently adapt and develop resistance because the broader survival system of the cell remains intact.
Cancer survival is governed at the system level by networks of survival genes that are essential for maintaining cellular viability. Survival genes are defined by function: loss or inhibition of a survival gene results in cell death regardless of cell type. These genes act as nodes within critical biological processes, including metabolism, protein homeostasis, DNA repair, and cellular stress response. Because these processes are required for basic cellular function, disruption of these processes results in loss of cellular viability and cell death.
As tumors progress, cancer cells experience elevated cellular stress due to increased demands on essential cellular processes such as metabolism and RNA processing. In response to these demands, cancer cells increase survival gene expression. The increased expression of survival genes expands the number of survival gene targets available for therapeutic disruption.
Cancer originates from normal cells, but to become malignant those cells must escape the controls that maintain normal cellular function. Normal cells maintain high expression of small regulatory RNAs called microRNAs (miRNAs), which enforce RNA-based gene regulation and lock in normal cellular behavior. High miRNA expression also protects survival gene expression.
Cancer cells are not normal cells. Cancer must lose this regulatory control to become malignant. Loss of this regulatory lock significantly lowers susceptibility to survival gene disruption while normal cells remain protected.
Loss of RNA regulatory control is therefore not merely a feature of cancer progression—it is a prerequisite for malignancy. This biological shift creates the conditions that allow survival gene disruption to preferentially impact malignant cells.
We did not design selectivity. It is fundamental biology. Selectivity is a direct consequence of the malignant state.
Mechanism of Action
NUAgo develops single-construct short RNA (sRNA) therapeutics that simultaneously reduce expression of multiple survival genes through RNA interference (RNAi). Survival genes are targeted by unique seed sequences within a 19nt sRNA, enabling coordinated suppression of a group of survival genes.
This coordinated disruption reduces survival capacity at the network level. When the survival gene network is sufficiently disrupted, the cellular systems required for survival fail, collapsing the cell’s survival system.
This collapse engages a conserved cell death response known as Death Induced by Survival gene Elimination (DISE), a system-level execution outcome driven by simultaneous loss of essential survival functions.
Our approach disrupts cancer’s survival at the system level rather than inhibiting individual targets or signaling pathways.
Platform Approach
The biological conditions that enable this therapeutic strategy are shared across solid tumors. Cancer cells must reduce miRNA expression to become malignant, and this reduced expression is observed across solid tumors.
Once the biological basis for cancer cell vulnerability is understood, the platform logic becomes straightforward. NUAgo exploits the global reduction in microRNA expression in cancer cells to deliberately target cancer’s survival system.
The platform comprises hundreds of optimized short RNA (sRNA) sequences that engage survival gene networks. These sequences are tailored by cancer type rather than patient-specific mutations, allowing therapeutic programs to be optimized for the survival gene context of each cancer.
The breadth of optimized sRNA sequences enables scalable program development across tumor types.
Because this malignant condition is shared across solid tumors, the same platform logic enables repeatable, system-level disruption of cancer survival across multiple tumor types.