Provided are compositions related to HSD17B13 variants, including nucleic acid molecules and polypeptides related to variants of HSD17B13, and cells comprising those nucleic acid molecules and polypeptides. Also provided are methods related to HSD17B3 variants. Such methods include methods for detecting the presence of the HSD17B13 rs72613567 variant in a biological sample comprising genomic DNA, for detecting the presence or levels of any one of variant HSD17B13 Transcripts C, D, E, F, G, and H, and particularly D, in a biological sample comprising mRNA or cDNA, or for detecting the presence or levels of any one of variant HSD17B13 protein Isoforms C, D, E, F, G, or H, and particularly D, in a biological sample comprising protein. Also provided are methods for determining a subject's susceptibility to developing a liver disease or of diagnosing a subject with liver disease.

Provided are compositions related to HSD17B13 variants, including isolated nucleic acids and proteins related to variants of HSD17B13, and cells comprising those nucleic acids and proteins. Also provided are methods related to HSD17B13 variants. Such methods include methods for modifying a cell through use of any combination of nuclease agents, exogenous donor sequences, transcriptional activators, transcriptional repressors, and expression vectors for expressing a recombinant HSD17B13 gene or a nucleic acid encoding an HSD17B13 protein. Also provided are therapeutic and prophylactic methods for treating a subject having or at risk of developing chronic liver disease.

Disclosed herein are short interfering nucleic acid (siNA) molecules comprising modified nucleotides and uses thereof. The siNA molecules may be double stranded and comprise modified nucleotides selected from 2-O-methyl nucleotides and 2-fluoro nucleotides. Further disclosed herein are siNA molecules comprising additional modification including a phosphorylation blocker, conjugated moiety, or 5-stabilized end cap. The siNA molecules may reduce or inhibit the production of hydroxysteroid dehydrogenase.

The present disclosure provides HSD17B13-related double stranded oligonucleotides, compositions, and methods of using such double stranded oligonucleotides and compositions for preventing and/or treating various conditions, disorders, or diseases associated with expression of HSD17B13. In some embodiments, the provided double stranded oligonucleotides and compositions comprise nucleobase modifications, sugar modifications, internucleotidic linkage modifications and/or patterns thereof, and have improved properties, activities and/or selectivities. In some embodiments, the provided double stranded oligonucleotides and compositions target HSD17B13.

The invention relates to methods of treating subjects that would benefit from reduction in expression of HSD17B13, such as subjects having a HSD17B13-associated disease, disorder, or condition, e.g., nonalcoholic steatohepatitis (NASH), using double-stranded ribonucleic acid (dsRNA) compositions targeting the HSD17B13 gene. The invention also provides methods for preventing at least one symptom in a subject having a HSD17B13-associated disease, disorder, or condition, e.g., NASH.