Fuente: WIPO "tomato" Described herein are compositions, systems, and methods for modulating gene expression. Also described herein are systems and methods for treating a disease or a condition by modulating gene expression. In some embodiments, the compositions, systems, and methods provided herein are used to treat familial hypercholesterolemia. In some embodiments, the compositions, systems, and methods provided herein involve suppression of endogenous PCSK9.