Genome editing in nonhuman primates: approach to generating human disease models

Area of Science:

• Biomedical Research
• Genomics
• Primate Models

Background:

• Nonhuman primates (NHPs) share significant genetic and physiological similarities with humans, making them valuable disease models.
• Transgenic animals are crucial for disease modeling and drug validation, but NHP model development has faced technological hurdles.
• Many human diseases stem from endogenous gene mutations, necessitating advanced modeling techniques.

Purpose of the Study:

• To review the advancements in generating transgenic nonhuman primate models for human diseases.
• To highlight the impact of precision gene editing technologies on NHP model creation.
• To compare the efficacy of NHP models with traditional rodent models for human disease research.

Main Methods:

• Utilizing precision gene editing tools, including transcription activator-like endonucleases (TALENs) and CRISPR/Cas9.
• Generating genetically modified monkey models to study human diseases.
• Analyzing NHP models for disease symptom fidelity and off-targeting effects.

Main Results:

• Recent gene editing advancements have enabled the creation of NHP models for various human diseases.
• Generated NHP models exhibit symptoms more closely resembling human conditions than existing rodent models.
• No off-targeting effects were observed in the developed NHP models, with successful generation of multiple gene knockouts and biallelic mutants.

Conclusions:

• Precision gene editing has overcome previous limitations in creating transgenic NHP models.
• NHP models hold significant potential for faithfully mimicking human diseases, surpassing rodent models.
• These advanced NHP models can accelerate functional genomics, disease research, and drug development.