Many cancers have recurrent chromosomal translocations leading to the fusion of two genes. Often, said cancers are aggressive, have a poor prognosis with metastasis or recurrence, and do not have effective and targeted treatment. The challenge of many fusion-positive cancers is the lack of established targets downstream of the
gene fusion despite years of intensive research to understand the biology of the gene fusion. Approaches to develop more targeted therapeutics focus on unique molecular pathways or programming the immune system, which are not only expensive, but require a lot of time to develop.
Researchers at Arizona State University in conjunction with collaborators at The Jackson Laboratory developed novel RNA sensor platform which targets chromosomal fusions, mutant genes and/or viral transcripts. These RNA sensors detect sequences on either side of the target to increase detection specificity. The RNA sensors can trigger programmed downstream events such as apoptosis, expression of immunostimulatory proteins or other therapeutic functions upon binding. This platform technology may be readily reprogrammed to target many different types of cancers harboring fusion genes and transcripts. It targets only cancer cells with the fusion and saves significant time by eliminating the need to study the biology of the fusion before developing relevant therapeutics.
This RNA sensor platform detects specific nucleic acid sequences related to cancer, such as mutant genes, chromosomal fusions, and viral transcripts and then initiates a therapeutic response to mitigate the effects of these anomalies, offering a precise, rapid, and cost-effective treatment option.
Potential Applications
- Targeted cancer therapy
- Particularly suited for fusion-positive cancers such as EWS, infant AML, ST-EPN and more
- Identification of genetic anomalies in cancer cells
- Cancer biology and genetics research tool
Benefits and Advantages
- High specificity in targeting genetic anomalies in cancer cells
- Rapid deployment and cost-effective compared to traditional cancer treatments
- Does not require extensive study of the gene fusion or transcript before developing therapeutics
- Ability to initiate downstream therapeutic functions upon binding including expression of immunostimulatory proteins, activation of a prodrug, as well as cytotoxic events such as apoptosis
- Can be readily reprogrammed to target different cancers harboring fusion genes and transcripts
- Is based on intrinsic cellular RNA editing activities by endogenous adenosine deaminases acting on RNA (ADR) or exogenously providing recombinant engineered ADAR enzymes