Value Proposition:
- Specific targeting of mutations can treat any cancer with the specified mutations.
- Selective cell killing spares healthy tissue while eliminating cancer cells.
- Pan-cancer efficacy as guide RNAs are developed to target a wide breadth of cancer-specific mutations.
- Lack of protospacer adjacent motif (PAM) sites in healthy host cells prevents any undesired editing.
- Potential first-in-class therapeutic oncology strategy
Unmet Need:
Cancer treatments such as chemotherapy, radiation, surgery, and immunotherapy may not be effective options for resistant, recurrent, or refractory cancers. CAR T cells offer another treatment option, but their high cost and limited long-term efficacy may preclude their use in some patients. Finally, all treatment options produce off-target toxicity or injury, damaging healthy tissue inadvertently affected by cytotoxicity or surgical damage. As such, there is an unmet need for specific and selective cancer treatment options that can be employed in as many cancer contexts as possible.
Technology Description:
Researchers at Hopkins are developing a CRISPR/Cas9-based cell killing technology that targets mutations specific to cancer cells. CRISPR/Cas9 can be targeted to cancer-specific sequences, resulting in DNA damage only in cancer cells. This technology would spare healthy cells, reducing the amount of non-specific damage sustained by healthy tissue during treatment. This platform can be used in any cancer with tumor-specific DNA sequences, expanding the scope of use to many cancer contexts. Guide RNAs can be developed to target unique patient sequences, opening the door to a new generation of personalized medicine. This technology can also be used in combination with current cancer treatments or synergizes with novel small molecule inhibitors, further enhancing therapeutic selectivity.
Stage of Development: Proof-of-concept has been demonstrated in cell lines with/without small molecule inhibitors, and experiments in mouse models are ongoing.
Data Availability: Data available upon request.
Publication:
- CRISPR-Cas9 for Selective Targeting of Somatic Mutations in Pancreatic Cancers (Preprint). https://pubmed.ncbi.nlm.nih.gov/37131822/
- Mechanism of Delayed Cell Death Following Simultaneous CRISPR-Cas9 Targeting in Pancreatic Cancers (Preprint). https://pubmed.ncbi.nlm.nih.gov/37066222/
- Islands of genomic stability in the face of genetically unstable metastatic cancer (Preprint). https://pubmed.ncbi.nlm.nih.gov/38352348/
Related Technology: JHU Ref. C17201
