General considerations and case analysis of non-clinical studies of oligonucleotide therapeutics
FENG Zheng
YUE Yan
LI De-li
LIU Qi-yao
FAN A-li
HUANG Fang-hua
GONG Xin-jiang
Abstract：As an emerging therapeutic approach,oligonucleotide therapeutics(ONTs)have shown good application prospects and development potential in the fields of rare diseases and some chronic diseases.At present,20 ONTs have been approved globally,mainly including antisense oligonucleotides(ASO),small interfering RNAs(siRNA),and aptamer,with more and more ONTs entering the clinical development stage.The industry has accumulated relatively rich experience in ONTs sequence design,chemical modification,delivery system,etc.,but there is still a lack of systematic understanding of non-clinical safety evaluation,and no consistent global regulatory requirements have been formed yet.This article comprehensively investigated the main sources of toxicity of ONTs and their causing factors,as well as the non-clinical experiences of FDA-approved ASO and siRNA drugs,and elaborated the research contents and general considerations of ONTs non-clinical safety evaluation,in order to provide reference for the research and development of ONTs in China.
Keywords：oligonucleotide therapeuticsnon-clinical studysafety assessmentgeneral considerations
Publication Date：2024-12-15
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：10( 2446-2455 )