2022-0208

Next Generation of the mRNA Therapy: Targeting Cancer Cells Via Boolean Circuits Based on mRNA Molecules

Currently most cancer treatment target proteins that are modified or activated in cancer cells; usually this is done by producing a relevant antibody. The process of finding a new therapy that targets a protein is long and tedious and in addition, in many cancer types there is no therapy at all. Specifically, today there are almost no therapies that target silent cancer mutations that do not affect the amino acid sequences.
Now, the use of RNA as a therapeutic tool is a new frontier in the broad view of disease treatment and prevention. RNA-based therapies hold the potential to revolutionize fields such as vaccines, personalized medicine and cancer therapy. Since RNA is easy to manufacture, safe, modular, cost effective and holds the ability to target previously untreatable pathologies, RNA-based treatments could serve as the future standard in medicine.
One of the big challenges such treatments face is the lack of specificity in the case of cancer therapy. Current delivery methods are general, where the RNA molecules are delivered with nonspecific vehicles and arrive not only to the cells we wish to target, but to many additional cells. In that case, we get expression of our protein of interest in unwanted cells, which can result in high toxicity.
Here we suggest a new approach for automatic design of mRNA therapies which based on logic gates that are opened by cancerous mRNA. The logic gates are based on toehold switches that are designed based on comprehensive computational pipeline. The gates can be opened by combinations silent mutations, splicing mutations, and non-silent mutations that appear only in the target cancer cell. The approach can be used to design automatically new cancer treatments but also for improving mRNA vaccines and for gene therapy.

UNMET NEED
Currently most cancer treatment target proteins that are modified or activated in cancer cells; usually this is done by producing a relevant antibody. However, a large fraction of the cancerous mutations is silent (i.e. they do not affect the encoded proteins); today there are almost no therapies that target such silent cancer mutations.

OUR SOLUTION
We suggest a new approach for automatic design of mRNA-based therapies which are based on logic gates that are opened by cancerous mRNA. The logic gates are based on toehold switches that are designed based on comprehensive computational pipeline. The gates can be opened by combinations silent mutations, splicing mutations, and non-silent mutations that appear only in the target cancer cell. The approach can be used to design automatically new cancer treatments but also for improving mRNA vaccines and for gene therapy.

APPLICATIONS
– Cancer therapeutics (for any type of cancer).
– Various applications in biotechnology such as biosensors, metabolic engineering, etc
STATUS
We developed a model and have a POC in an eukaryotic system.

INTELLECTUAL PROPERTY
Two patent applications and know-how.
Ramot refs. 2022-069 and 2024-013

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