Future directions and challenges of drug development and non-human primate models
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Updated: Nov 7, 2026

Preparation and Gene Modification of Nonhuman Primate Hematopoietic Stem and Progenitor Cells
Published on: February 15, 2019
1Department of Institute of Laboratory Animal Sciences, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610212, China.
Aims:
Gene and cell therapy are transforming therapeutic approaches for genetic diseases and malignancies. This review examines the current role and future directions of non-human primate (NHP) models in preclinical safety evaluation of adeno-associated virus (AAV) gene therapy and chimeric antigen receptor T-cell (CAR-T) therapy amid accelerating adoption of new approach methodologies (NAMs).
Materials And Methods:
We systematically searched PubMed, Web of Science, Embase, and the China National Knowledge Infrastructure for publications from January 2015 to June 2026; approximately 60 English-language and 5 Chinese-language publications, together with FDA, EMA, and NMPA guidance documents, were included.
Key Findings:
NHPs remain the reference species for AAV and CAR-T safety evaluation, yet supply crises, ethical pressures, and documented prediction gaps (hepatotoxicity, dorsal root ganglion injury) are driving NAMs adoption. Organoids, organs-on-chips (87% sensitivity and 100% specificity for drug-induced liver injury), and AI-driven models are maturing under the FDA Modernization Act 2.0 and the 2025 FDA roadmap.
Significance:
We propose the Hierarchical Replacement Assessment Framework (HRAF), a three-tier, two-threshold model that reallocates NHP resources from routine screening to risk confirmation, providing an actionable roadmap for mechanism-based and welfare-conscious preclinical development.
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