Selective Cell Elimination using RNA-guided Chromatin Shredding

Patent Status

Patent Pending

Brief Description

Cancer is driven by genetic mutations, notably in p53, which is altered in ~ nearly half of all cancers and up to 70–90% of cases of some of the most difficult-to-treat cancers, including ovarian, pancreatic, and non-small cell lung cancer. P53 mutations also tend to be clonal, arising early and persisting across tumor cells in a heterogenous population. Restoring p53 function for tumor regression has been considered the "holy grail" of cancer therapy. However, no approved therapies are available to target the p53 protein due to its lack of druggable pockets and the difficulty of re-activating defective transcription factors. Conventional treatments, like chemotherapy, induce systemic DNA damage, leading to widespread side effects. Therefore, there is a need for compositions and methods that address the above.

UC Berkeley researchers and collaborators at Utah State University and the University of Utah have developed methods and compositions for cleaving chromosomal DNA in a eukaryotic cell that address some of the problems with cancer therapies mentioned above. The newly engineered CRISPR-Cas12a2 system detects a cancer signature within a cell and the Cas12a2 enzyme activates and initiates “chromatin shredding,” slicing up all the genetic material inside that specific cell. This widespread genetic demolition triggers cell death, destroying mutated cells while leaving healthy cells completely untouched.

Suggested uses

Advantages

• RNA-guided Cas12a2 senses cellular RNA signatures to shred chromatin, enabling precise targeting of undruggable mutations
• Does not need to bind to the protein; system destroys the cell based on its genetic signature
• Can kill highly mutated or treatment-resistant cancer cells that survive chemotherapy