Abstract
Many neurodegenerative diseases are caused by unstable trinucleotide repeat (TNR) expansions located in disease-associated genes. siRNAs based on CAG repeat expansions effectively kill cancer cell lines in vitro through RNAi. They also cause significant reduction in tumor growth in a human ovarian cancer mouse model with no toxicity to the treated mice. This suggests that cancer cells are particularly sensitive to CAG TNR-derived siRNAs, and explains a reported inverse correlation between the length of CAG TNRs and reduced global cancer incidences in some CAG TNR diseases. This review discusses both mutant proteins and mutant RNAs as a cause of TNR diseases, with a focus on RNAi and its role in contributing to disease pathology and in suppressing cancer.