Genetically modified animals are vital for gaining a proper understanding of disease mechanisms. Mice have long been the mainstay of basic research into a wide variety of diseases but are not always the most suitable means of translating basic knowledge into clinical application. The shortcomings of rodent preclinical studies are widely recognised, and regulatory agencies around the world now require preclinical trial data from nonrodent species. Pigs are well suited to biomedical research, sharing many similarities with humans, including body size, anatomical features, physiology and pathophysiology, and they already play an important role in translational studies. This role is set to increase as advanced genetic techniques simplify the generation of pigs with precisely tailored modifications designed to replicate lesions responsible for human disease. This article provides an overview of the most promising and clinically relevant genetically modified porcine models of human disease for translational biomedical research, including cardiovascular diseases, cancers, diabetes mellitus, Alzheimer's disease, cystic fibrosis and Duchenne muscular dystrophy. We briefly summarise the technologies involved and consider the future impact of recent technical advances.

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Genetically engineered pigs as models for human disease.

AAV5-miHTT Gene Therapy Demonstrates Broad Distribution and Strong Human Mutant Huntingtin Lowering in a Huntington's Disease Minipig Model.

Animal models of closed-skull, repetitive mild traumatic brain injury.

Translation of MicroRNA-Based Huntingtin-Lowering Therapies from Preclinical Studies to the Clinic.

Genetically modified rodent models of Huntington's disease (HD) have been especially valuable to our understanding of HD pathology and the mechanisms by which the mutant HTT gene alters physiology. However, due to inherent differences in genetics, neuroanatomy, neurocircuitry and neurophysiology, animal models do not always faithfully or fully recapitulate human disease features or adequately predict a clinical response to treatment. Therefore, conducting translational studies of candidate HD therapeutics only in a single species (i.e. mouse disease models) may not be sufficient. Large animal models of HD have been shown to be valuable to the HD research community and the expectation is that the need for translational studies that span rodent and large animal models will grow. Here, we review the large animal models of HD that have been created to date, with specific commentary on differences between the models, the strengths and disadvantages of each, and how we can advance useful models to study disease pathophysiology, biomarker development and evaluation of promising therapeutics.

Large Animal Models of Huntington's Disease: What We Have Learned and Where We Need to Go Next.

Behavioral phenotyping of minipigs transgenic for the Huntington gene.

The Libechov Minipig as a Large Animal Model for Preclinical Research in Huntington’s disease – Thoughts and Perspectives

Neuroimaging of a minipig model of Huntington's disease: Feasibility of volumetric, diffusion-weighted and spectroscopic assessments

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Behavioral phenotyping of minipigs transgenic for the Huntington gene.

The Libechov Minipig as a Large Animal Model for Preclinical Research in Huntington’s disease – Thoughts and Perspectives

Neuroimaging of a minipig model of Huntington's disease: Feasibility of volumetric, diffusion-weighted and spectroscopic assessments