臓器特異的リキッドバイオプシーを用いたエピジェネティクス解析による薬物動態関連遺伝子の機能予測

抄録

Drug metabolizing enzymes and transporters are increasingly recognized as key determinants of the inter-individual variability in the pharmacokinetic outcomes of clinically important drugs. In order to facilitate subject phenotyping, various endogenous compounds in plasma have been pursued as drug metabolizing enzyme and transporter biomarkers. Compared with biomarkers, however, the topic of liquid biopsy has received little attention within the pharmacokinetic community. Liquid biopsy refers to the sampling and molecular analysis of biofluids such as cells, exosomes, and nucleic acids that originated from a solid organ and entered the bloodstream. ​Recently, we established a method for organ-specific isolation of the exosomes and cells from blood. In this presentation, we report on the analysis of intestine-derived exosomes and liver-derived cells as the separation of organ-specific biofluids. Intestine-derived exosomes were obtained by immunoprecipitation with glycoprotein A33, an intestine-specific membrane antigen. We analyzed the function of the drug transporter breast cancer resistance protein by the clinical study using intestine-derived exosomes. Liver-derived cells were isolated from peripheral blood mononuclear cells by immunoprecipitation with asialoglycoprotein receptor, a liver-specific membrane antigen. Based on the analysis of DNA extracted from liver-derived cells, a clinical study was conducted to analyze the function of the metabolic enzyme cytochrome P450 3A4 in the liver. An important advantage of liquid biopsy is that the ability to obtain exosomes and cells from blood makes it easier to obtain the consent of the subjects and to conduct clinical studies.