Scientists from University of Pittsburgh have developed a novel approach to target cancer cells through the insertion of a “suicide gene” (HSV1-tk) into key gene fusion areas of the cancer genome.
Targeting gene fusion points remains an elusive goal in cancer therapy. This novel approach can insert HSV1-tk at specific fusion points and could lead to improved survival in cancer patients through initiation of cell death or metastasis inhibition, personalized to each patient’s unique cancer.
Advantages:
Research has identified a panel of fusion genes present in various cancers including hepatocellular carcinoma (HCC)
Using a tailored Cas9-based genome editing approach it is possible to selectively insert the gene HSV1-tk to the fusion point
Creation of this unique breakpoint, present only in cancer tissue provides a target for therapeutic intervention which is less likely to result in drug resistance through gene mutation
This approach has been studied in TMEM135-CCDC67 in human prostate cancer highlighting this potential of genome editing to provide a genotype-specific approach to treat various cancersTechnology Readiness:
Using two uniquely designed guide RNA (gRNA) strands and a newly developed Cas9-mediated genome editing approach, HSV1-tk has been successfully inserted into various gene mutations commonly found in human cancers in both cell and mice studies. Introduction of HSV1-tk treatment with the anti-herpes drug ganciclovir led to cell death in vitro and reduction of tumor size and mortality in mice. Of note, significant side effects were not observed.Commercialization Potential:
Two fusion gene breakpoints have been successfully targeted with an HSV gene. Treatment with antivirals led to cell death in vivo and improved mortality in vitro. Further work is required to develop clinical feasibility and identify other potential targets or insertion genes.Inventors:
Jianhua Luo, MD, PhD
Satdarshan (Paul) Singh Monga, MD
Shuchang Liu, PhD
Junyan Tao, PhD