Abstract: Provided herein are compositions and methods for inhibiting the expression and/or activity of kallikrein-related peptidase (KLK) (e.g., KLK5 and KLK7) genes and/or KLK (e.g., KLK5 and KLK7) gene products using oligonucleotide-based therapy. In some embodiments, the compositions are spherical nucleic acids (SNAs) targeting a region of a KLK5 gene and/or gene product and a second synthetic oligonucleotide targeting a region of a KLK7 gene and/or a KLK7 gene product. Such compositions and methods are useful, for instance, in the treatment, prevention, and/or amelioration of diseases or disorders associated with the dysregulation of KLK function.