Abstract.
Telomerase is silent in most normal somatic cells while active in over 90% cancer cells. Therefore, various telomerase activity inhibitors have been developed to treat cancers but all failed. In our project, we acted oppositely to develop a cancer gene therapy by utilizing the telomerase activity in cancer cells. We constructed a telomerase-activating gene expression system to induce cancer cell death. In this system, a vector ended with a telomerase-recognizable end can be elongated by telomerase, which will provide a telomeric repeat sequence that can be bound by a telomeric DNA-targeting dCas9-VP64-sgRNA. This binding will activate expression of an effector gene Cas9. The produced Cas9 protein can then be targeted to the telomeres of cancer cell chromosomes by a telomere-targeting sgRNA, which will produce the DNA damage and lead to cancer cell death. However, due to no telomerase activity, this system will not affect normal cells.