Abstract: Described herein are compounds, compositions, and methods for modulating KRAS expression, such as mutated KRAS expression, and/or downstream signaling pathways. Also described herein are compounds, compositions, and methods for treating a disease or condition associated with mutated KRAS. In some embodiments, the compound comprises at least one antisense oligonucleotide that, upon being delivered into a cell, hybridizes to an endogenous KRAS mRNA, which leads to the degradation of the KRAS mRNA. In some embodiments, the antisense oligonucleotide hybridizes to an mRNA encoding a mutated KRAS protein, such as a KRAS protein comprising a G12C mutation, a G12V mutation, a G12D mutation, or a G12A mutation.

Abstract: This application provides polynucleotides comprising a coding sequence for a functionally active hereditary hemochromatosis protein (HFE) or a functionally active fragment thereof. The invention further provides compositions comprising said polynucleotides and their use in methods of preventing or treating hemochromatosis in a subject.