ICT2025 - lUTOX 17th International Congress of Toxicology

Date	Time	Local Time	Room	Forum	Session	Role	Topic
2025-10-17	14:20-14:30	2025-10-17,14:20-14:30	Room A - Guojin Hall	Symposium Program （Session）	Young Scientist Lecture 03：Artificial Intelligence Toxicology and New Technologies and Methods	Speaker	Constructing a Model for Evaluating Pulmonary Toxicity of Environmental Pollutants Using Gene Editing Technology Abstract: Chronic obstructive pulmonary disease (COPD) is a severe respiratory disorder that significantly impairs lung function and ranks as the third leading cause of death globally. The primary causes of COPD include prolonged exposure to cigarette smoke and pollutants, as well as genetic factors such as α-1 antitrypsin deficiency. Encoded by the SERPINA1 gene, α-1 antitrypsin is a protective protein that shields lung tissue from inflammatory damage. Epidemiological studies indicate that individuals with pre-existing conditions are more vulnerable to environmental pollutants; however, effective models for investigating the susceptibility mechanisms of COPD patients to environmental pollutants remain lacking. This study established a SERPINA1-knockout human pluripotent stem cell line to differentiate human alveolar type II epithelial cells, thereby simulating the pulmonary physiological state of COPD patients. We employed CRISPR-Cas9 technology to construct a SERPINA1-knockout human pluripotent stem cell line. Dual-site cleavage targeting the first exon of the gene induced fragment deletion and frameshift mutations to disrupt gene function. Sequencing results confirmed fragment deletion in the target gene, accompanied by frameshift mutations that generated premature termination codons, leading to truncated mRNA translation. The established SERPINA1-knockout cell lines have been utilized for differentiating human alveolar type II epithelial cells and constructing a COPD-specific disease model. This model is specifically designed for pulmonary toxicity screening of environmental pollutants, particularly for identifying substances posing high risks to COPD patients. It enables exploration of cellular responses to various environmental pollutants and integrates omics and molecular biology approaches to elucidate the impact of environmental factors on genetically susceptible individuals. The development of this COPD-specific model will provide a physiologically relevant platform for assessing environmental exposures in patient populations.

Abstract: Chronic obstructive pulmonary disease (COPD) is a severe respiratory disorder that significantly impairs lung function and ranks as the third leading cause of death globally. The primary causes of COPD include prolonged exposure to cigarette smoke and pollutants, as well as genetic factors such as α-1 antitrypsin deficiency. Encoded by the SERPINA1 gene, α-1 antitrypsin is a protective protein that shields lung tissue from inflammatory damage. Epidemiological studies indicate that individuals with pre-existing conditions are more vulnerable to environmental pollutants; however, effective models for investigating the susceptibility mechanisms of COPD patients to environmental pollutants remain lacking. This study established a SERPINA1-knockout human pluripotent stem cell line to differentiate human alveolar type II epithelial cells, thereby simulating the pulmonary physiological state of COPD patients.

We employed CRISPR-Cas9 technology to construct a SERPINA1-knockout human pluripotent stem cell line. Dual-site cleavage targeting the first exon of the gene induced fragment deletion and frameshift mutations to disrupt gene function. Sequencing results confirmed fragment deletion in the target gene, accompanied by frameshift mutations that generated premature termination codons, leading to truncated mRNA translation. The established SERPINA1-knockout cell lines have been utilized for differentiating human alveolar type II epithelial cells and constructing a COPD-specific disease model. This model is specifically designed for pulmonary toxicity screening of environmental pollutants, particularly for identifying substances posing high risks to COPD patients. It enables exploration of cellular responses to various environmental pollutants and integrates omics and molecular biology approaches to elucidate the impact of environmental factors on genetically susceptible individuals. The development of this COPD-specific model will provide a physiologically relevant platform for assessing environmental exposures in patient populations.