Safety Testing of an Antisense Oligonucleotide Intended for Pediatric Indications in the Juvenile Gottingen Minipig, including an Evaluation of the Ontogeny of Key Nucleases.

ABSTRACT: The adult Göttingen Minipig is an acknowledged model for safety assessment of antisense oligonucleotide (ASO) drugs developed for adult indications. To assess whether the juvenile Göttingen Minipig is also a suitable nonclinical model for pediatric safety assessment of ASOs, we performed an 8-week repeat-dose toxicity study in different age groups of minipigs ranging from 1 to 50 days of age. The animals received a weekly dose of a phosphorothioated locked-nucleic-acid-based ASO that was assessed previously for toxicity in adult minipigs. The endpoints included toxicokinetic parameters, in-life monitoring, clinical pathology, and histopathology. Additionally, the ontogeny of key nucleases involved in ASO metabolism and pharmacologic activity was investigated using quantitative polymerase c

SUBMITTER: Valenzuela A 

PROVIDER: S-EPMC8470776 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature