Veterinary Pathology Spring webinar series - 5

Talk 1: Pathology findings associated with therapeutic oligonucleotides in lab animal species

RNA‑targeting therapeutics, including antisense oligonucleotides (ASOs) and small interfering RNA (siRNA), are synthetic nucleic acids designed to modulate gene expression by binding specific RNA sequences. Through distinct mechanisms of action, these agents can modulate the synthesis of proteins. Major advances in oligonucleotide chemistry have led to favorable safety profiles and the regulatory approval of 14 ASO and 8 siRNA therapeutics over the past three decades. However, toxicological findings remain a key challenge in preclinical development and are largely driven by the chemical modifications incorporated in the synthetic oligonucleotide sequence. This talk outlines the general principles and mechanisms of action of ASO and siRNA therapeutics and highlights representative toxicity considerations encountered during preclinical drug development.

Talk 2: Pathology Findings Associated with Telemetry Device in Beagle dogs

Telemetry-instrumented beagle dogs are implemented during cardiovascular safety assessment in early drug development for the collection of cardiovascular function parameters such as electrocardiography, heart rate, mean arterial pressure, and cardiac contractility to predict cardiovascular risk in humans, aligning with recommendations in ICH guidelines S7A and S7B. Telemetry implants provide a sensitive and robust method for monitoring arterial blood pressure in dogs and it is important to take into account procedural-related pathology when dogs are reallocated in other exploratory toxicology studies as part of 3R for animal use in research.  The objectives of the talk aim to discuss procedural-related macroscopic and histopathological changes in chronically-implanted telemetry device dogs.