CRISPR/Cas9-Mediated Gene Editing in Porcine Models for Medical Research.

Pigs have been extensively used as the research models for human disease pathogenesis and gene therapy. They are also the optimal source of cells, tissues, and organs for xenotransplantation due to anatomical and physiological similarities to humans. Several breakthroughs in gene-editing technologies, including the advent of clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated 9 (Cas9), have greatly improved the efficiency of genetic manipulation and significantly broadened the application of gene-edited large animal models. In this review, we have not only outlined the important applications of the CRISPR/Cas9 system in pigs as a means to study human diseases but also discussed the potential challenges of the use of CRISPR/Cas9 in large animals.

[Research progress of producing genetically modified pigs by CRISPR/Cas9 in the medical field].

As pigs are similar to humans in anatomy, physiology and pathology, nutrition metabolism and disease characteristics, genetically modified pigs are already used for the studies of disease mechanism, pathology and toxicology and the evaluation of drugs. But the production of large modified animals is difficult, cumbersome, time-consuming and costly. With the breakthrough of gene editing technology, clustered regularly interspersed short palindromic repeat (CRISPR)/CRISPR-associated 9( Cas9)(CRISPR/Cas9) technology has greatly improved the mutation efficiency, reduced the cost and simplified the steps, and promoted the widespread application of genetically modified pigs. In this paper, the production methods of genetically modified pigs and the research progress of genetically modified pigs by CRISPR/Cas9 in the medical field were reviewed.

Chronic Pulmonary Artery Embolization Models in Large Animals.

A wide range of approaches have been described to develop animal models of pulmonary vascular disease (PVD). Clinical heterogeneity in patients with pulmonary hypertension (PH) has prompted development of different techniques to create PH models in several animal species with the objective to recapitulate specific PH/PVD phenotypes. Chronic thromboembolic PH (CTEPH) is a clinically important phenotype of PH with a documented prevalence of 0.4-9.1% in patients with history of pulmonary embolism. A well-established large animal model of CTEPH is thus necessary for studying this disease in preclinical research. Different experimental protocols with inconsistent outcomes have been reported in the literature.We have focused on characterizing PH large animal models in a common framework; pulmonary hemodynamics, right ventricular (RV) function, and histological characterization of PVD. This research framework allows optimal evaluation of novel diagnostic tools, as well as new therapeutic strategies. The purpose of this protocol is to describe approaches to create experimental CTEPH models using recurrent pulmonary embolizations of dextran microspheres in swine. The key features of this experimental modeling approach are (1) nonsurgical, fully percutaneous techniques, (2) a minimum of four embolization procedures, with 1-2 month time period, (3) mild to moderate PH hemodynamics (mean PA pressure increase ~20-60%), (4) severe pulmonary vascular remodeling, (5) mild RV remodeling, and (6) a high reproducibility and low mortality (<10%).

Research progress of producing genetically modified pigs by CRISPR/Cas9 in the medical field / 生物医学工程学杂志

As pigs are similar to humans in anatomy, physiology and pathology, nutrition metabolism and disease characteristics, genetically modified pigs are already used for the studies of disease mechanism, pathology and toxicology and the evaluation of drugs. But the production of large modified animals is difficult, cumbersome, time-consuming and costly. With the breakthrough of gene editing technology, clustered regularly interspersed short palindromic repeat (CRISPR)/CRISPR-associated 9( Cas9)(CRISPR/Cas9) technology has greatly improved the mutation efficiency, reduced the cost and simplified the steps, and promoted the widespread application of genetically modified pigs. In this paper, the production methods of genetically modified pigs and the research progress of genetically modified pigs by CRISPR/Cas9 in the medical field were reviewed.