Hybrid Mouse Diversity Panel Identifies Genetic Architecture Associated with the Acute Antisense Oligonucleotide-Mediated Inflammatory Response to a 2'-O-Methoxyethyl Antisense Oligonucleotide.

ABSTRACT: Although antisense oligonucleotides (ASOs) are well tolerated preclinically and in the clinic, some sequences of ASOs can trigger an inflammatory response leading to B cell and macrophage activation in rodents. This prompted our investigation into the contribution of genetic architecture to the ASO-mediated inflammatory response. Genome-wide association (GWA) and transcriptomic analysis in a hybrid mouse diversity panel (HMDP) were used to identify and validate novel genes involved in the acute and delayed inflammatory response to a single 75 mg/kg dose of an inflammatory 2'-O-methoxyethyl (2'MOE) modified ASO. The acute response was measured 6 h after ASO administration, via evaluation for increased plasma production of interleukin 6 (IL6), IL10, monocyte chemoattractant protein 1

SUBMITTER: Pirie E 

PROVIDER: S-EPMC6765210 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature