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In Vivo Gene Transfer to the Rabbit Common Carotid Artery Endothelium
Published on: May 6, 2018
Large animal models and gene therapy
1School of Veterinary Medicine, University of Pennsylvania, Philadelphia, 19104-6051, USA.
Abstract:
Over the last two decades, gene transfer experiments for the treatment of inherited or acquired diseases have mainly been performed in mice. While mice provide proof of principle and allow testing of a variety of therapeutic modalities, mouse models have some limitations, as only short-term experiments can be performed, their homogenous genetic background is unlike humans, and the knockout models do not always faithfully represent the human disease. Naturally occurring large animal models of human genetic diseases have become increasingly important despite the costs and the extensive clinical attention they require because of their similarities to human patients. Large animals are reasonably outbred, long lived allowing for longitudinal studies, are more similar in size to a neonate or small child providing an opportunity to address issues related to scaling up therapy, and many physiological parameters including the immune system are more similar to those in humans versus those in mice.
Insights
Gene transfer studies in mice offer proof of principle but have limitations. Large animal models are increasingly vital for human disease research due to their physiological and genetic similarities, enabling long-term, scalable therapeutic studies.
Area of Science:
- Biomedical Research
- Gene Therapy
- Animal Models
Background:
- Gene transfer experiments for inherited and acquired diseases have predominantly used mouse models for two decades.
- Mouse models offer proof of principle for therapeutic modalities but have limitations including short experiment durations, homogenous genetic backgrounds, and imperfect representation of human diseases.
- Naturally occurring large animal models are gaining importance for studying human genetic diseases.
Purpose of the Study:
- To highlight the limitations of mouse models in gene transfer research.
- To emphasize the growing importance and advantages of large animal models in biomedical research.
- To discuss the suitability of large animals for longitudinal studies and scaling up gene therapies.
Main Methods:
- Review of existing literature on gene transfer experiments in mouse models.
- Comparison of physiological and genetic characteristics between mouse and large animal models.
- Analysis of the benefits of large animal models for long-term and translational studies.
Main Results:
- Mouse models have inherent limitations that may not fully translate to human disease.
- Large animal models offer greater genetic diversity, longer lifespans for longitudinal studies, and physiological similarities to humans.
- The size of large animals is advantageous for addressing scalability issues in gene therapy.
Conclusions:
- While mouse models are useful for initial gene transfer studies, their limitations necessitate the use of more relevant models.
- Large animal models provide a more accurate preclinical platform for gene therapy development due to their human-like physiology and genetic outbreeding.
- Further utilization of large animal models is crucial for advancing gene transfer therapies for human diseases.
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