Yafei Chen , Nathan Bivens , Hong An , Brian Mooney , Thao Nguyen , Lyndon Coghill , Jennifer Horkman , Lois Haupt , Melissa Evans , Rebecca Campbell , Wendell Davis
{"title":"介绍Sinclair Nanopig™模型:用于(生物)药物安全性评估的初步基因组学,蛋白质组学和肝脏CYP450表征","authors":"Yafei Chen , Nathan Bivens , Hong An , Brian Mooney , Thao Nguyen , Lyndon Coghill , Jennifer Horkman , Lois Haupt , Melissa Evans , Rebecca Campbell , Wendell Davis","doi":"10.1016/j.vascn.2025.108394","DOIUrl":null,"url":null,"abstract":"<div><div>The Nanopig™ model is an emerging non-rodent platform for (bio)pharmaceutical safety assessment, with potential advantages for translational research. Here, we report initial characterization results using whole genome sequencing (WGS) and tissue-based proteomics, focusing on drug metabolism and immune system relevance. WGS produced a high-quality Nanopig™ genome assembly (2.8–2.9 Gb), with >98 % alignment to the Duroc pig reference genome, and identified key metabolic and immune-related genes, including 47 cytochrome P450 (CYP450) genes with high homology to human CYP450 families. Proteomic profiling of 15 pharmaceutically relevant tissues revealed human orthologous drug metabolism enzymes and transporters (DMETs), as well as immune-related proteins, indicating similarities to human CYP450 enzyme abundance and tissue distribution. Functional evaluation of hepatic CYP450 activity yielded kinetic parameters (K<sub>m</sub>, V<sub>max</sub>) in the range observed in humans and beagle dogs. These early findings represent a foundational multi-omics dataset for the Nanopig™, suggesting its future use as a translational model in preclinical safety assessment. This work provides an early framework for species selection strategies and model optimization, with the long-term goal of reducing reliance on traditional non-rodent species in drug development.</div></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":"136 ","pages":"Article 108394"},"PeriodicalIF":1.8000,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Introducing the Sinclair Nanopig™ model: Preliminary genomic, proteomic, and hepatic CYP450 characterization for (bio)pharmaceutical safety assessment\",\"authors\":\"Yafei Chen , Nathan Bivens , Hong An , Brian Mooney , Thao Nguyen , Lyndon Coghill , Jennifer Horkman , Lois Haupt , Melissa Evans , Rebecca Campbell , Wendell Davis\",\"doi\":\"10.1016/j.vascn.2025.108394\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>The Nanopig™ model is an emerging non-rodent platform for (bio)pharmaceutical safety assessment, with potential advantages for translational research. Here, we report initial characterization results using whole genome sequencing (WGS) and tissue-based proteomics, focusing on drug metabolism and immune system relevance. WGS produced a high-quality Nanopig™ genome assembly (2.8–2.9 Gb), with >98 % alignment to the Duroc pig reference genome, and identified key metabolic and immune-related genes, including 47 cytochrome P450 (CYP450) genes with high homology to human CYP450 families. Proteomic profiling of 15 pharmaceutically relevant tissues revealed human orthologous drug metabolism enzymes and transporters (DMETs), as well as immune-related proteins, indicating similarities to human CYP450 enzyme abundance and tissue distribution. Functional evaluation of hepatic CYP450 activity yielded kinetic parameters (K<sub>m</sub>, V<sub>max</sub>) in the range observed in humans and beagle dogs. These early findings represent a foundational multi-omics dataset for the Nanopig™, suggesting its future use as a translational model in preclinical safety assessment. This work provides an early framework for species selection strategies and model optimization, with the long-term goal of reducing reliance on traditional non-rodent species in drug development.</div></div>\",\"PeriodicalId\":16767,\"journal\":{\"name\":\"Journal of pharmacological and toxicological methods\",\"volume\":\"136 \",\"pages\":\"Article 108394\"},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2025-09-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of pharmacological and toxicological methods\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1056871925008147\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of pharmacological and toxicological methods","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1056871925008147","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Introducing the Sinclair Nanopig™ model: Preliminary genomic, proteomic, and hepatic CYP450 characterization for (bio)pharmaceutical safety assessment
The Nanopig™ model is an emerging non-rodent platform for (bio)pharmaceutical safety assessment, with potential advantages for translational research. Here, we report initial characterization results using whole genome sequencing (WGS) and tissue-based proteomics, focusing on drug metabolism and immune system relevance. WGS produced a high-quality Nanopig™ genome assembly (2.8–2.9 Gb), with >98 % alignment to the Duroc pig reference genome, and identified key metabolic and immune-related genes, including 47 cytochrome P450 (CYP450) genes with high homology to human CYP450 families. Proteomic profiling of 15 pharmaceutically relevant tissues revealed human orthologous drug metabolism enzymes and transporters (DMETs), as well as immune-related proteins, indicating similarities to human CYP450 enzyme abundance and tissue distribution. Functional evaluation of hepatic CYP450 activity yielded kinetic parameters (Km, Vmax) in the range observed in humans and beagle dogs. These early findings represent a foundational multi-omics dataset for the Nanopig™, suggesting its future use as a translational model in preclinical safety assessment. This work provides an early framework for species selection strategies and model optimization, with the long-term goal of reducing reliance on traditional non-rodent species in drug development.
期刊介绍:
Journal of Pharmacological and Toxicological Methods publishes original articles on current methods of investigation used in pharmacology and toxicology. Pharmacology and toxicology are defined in the broadest sense, referring to actions of drugs and chemicals on all living systems. With its international editorial board and noted contributors, Journal of Pharmacological and Toxicological Methods is the leading journal devoted exclusively to experimental procedures used by pharmacologists and toxicologists.