Application of the transgenic pig model in biomedical research: A review

Abstract

The large animal model has gradually become an essential part of preclinical research studies, relating to exploring the disease pathological mechanism, genic function, pharmacy, and other subjects. Although the mouse model has already been widely accepted in clinical experiments, the need for finding an animal model with high similarity compared with a human model is urgent due to the different body functions and systems between mice and humans. The pig is an optimal choice for replacement. Therefore, enhancing the production of pigs used for models is an important part of the large animal model as well. Transgenic pigs show superiority in pig model creation because of the progress in genetic engineering. Successful cases of transgenic pig models occur in the clinical field of metabolic diseases, neurodegenerative diseases, and genetic diseases. In addition, the choice of pig breed influences the effort and efficiency of reproduction, and the mini pig has relative obvious advantages in pig model production. Indeed, pig models in these diseases provide great value in studies of their causes and treatments, especially at the genetic level. This review briefly outlines the method used to create transgenic pigs and species of producing transgenic pigs and provides an overview of their applications on different diseases and limitations for present pig model developments.

siRNA-mediated reduction of a circulating protein in swine using lipid nanoparticles

“… 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 Breeding transgenic swine mirrors the genetic knockout models utilized extensively in small animal species, but this process is time consuming, costly, and technically challenging. 13 , 51 , 52 , 53 , 54 Systemically delivered LNPs naturally target the liver, which produces 85%–90% of the total circulating blood protein volume 55 and thus contains numerous protein targets important in human health and disease. Here, we demonstrated a cost-friendly, convenient, and high-fidelity approach for in vivo genetic manipulation of swine, using plasminogen as a representative circulating protein.…”

Development and evaluation of an autism pig model

“…Future research employing transgenic pig models, especially those carrying mutations in high-risk genes of ASD, like SHANK3, FMR1, or NLGN3, could shed light on the disorder's molecular pathways and neural circuitry alterations. As transgenic techniques in pigs continue to advance 30 , these models will become more feasible and invaluable for testing the effectiveness of therapies aimed at these speci c genetic abnormalities.…”

Drug Screening and Validation Targeting TDP-43 Proteinopathy for Amyotrophic Lateral Sclerosis

“…The physiological structure and physiological function of large animals are more similar to humans, so they have higher reliability and accuracy in some disease simulations and drug testing [153]. Moreover, considering the physiological and metabolic reactions in pharmacokinetics, the body size and metabolic system of animals are closer to humans, so the drug development data obtained from them are more reliable [154]. At the same time, compared with human clinical experiments, extensive animal experiments can be carried out in a controlled environment, including diet, exercise, and environmental factors.…”