Animal models, particularly rodents, play a crucial role in studying liver transfection. These models help us understand how vectors behave in a living organism, assess safety and efficacy, optimize dosing strategies, and study the immune response to transgene and vector. Here are some commonly used animal models:
- Mice and Rats: These are the most commonly used models due to their ease of handling, relatively short lifespan, and well-characterized genetics. In terms of liver diseases, numerous transgenic, knockout, and chemically-induced models exist to mimic human liver diseases like hepatitis, liver fibrosis, and hepatocellular carcinoma. For instance, Fah knockout mice are often used to study hereditary tyrosinemia type 1.
- Rabbits and Guinea Pigs: These are larger animals that are sometimes used when larger amounts of liver tissue are needed for analysis or when certain procedures can’t be done in smaller animals.
- Pigs: Pigs have a similar size and anatomy to humans, and their liver physiology and regenerative capacity is closer to humans compared to rodents. Therefore, pigs are often used in preclinical studies for liver-directed gene therapies. For instance, pigs with hereditary tyrosinemia type 1 have been used to study the efficacy of CRISPR-Cas9 gene editing.
- Non-human Primates: These animals are genetically closer to humans and their liver size, structure, and function are similar to those of humans, which makes them a valuable model for preclinical studies. However, ethical considerations, high costs, and their long lifespan limit their use.
- Zebrafish: Zebrafish are increasingly used in liver research due to their rapid development, optical transparency during early development, and the ease of genetic manipulation. They have been used to model various liver diseases, including fatty liver disease and liver cancer.
Each animal model has its own advantages and limitations, and the choice of model depends on the specific question being asked. As of my knowledge cut-off in September 2021, research is ongoing to develop new animal models that more accurately mimic human liver diseases and to refine the existing models to reduce their limitations.