Ⅰ. Title
Prediction of absorption of orally applicable peptide/protein drug candidates fused with macromolecule transduction domain (MTD) using 2D human small intestinal epithelium model
Ⅱ. Purpose and necessity of research
Goal
Development of drug absorption prediction technology for orally administered protein/peptide drug candidates fused with MTD using a two-dimensional functional human intestine epithelial cell model
The need for research
A two-dimensional functional intestinal epithelial cell model and evaluation test method have been required to solve the company's demanded technology due to the absence of a proper cell model and evaluation test method that can evaluate the absorption rate of orally administered protein/peptide drugs in the small intestine .
Ⅲ. Content and scope of R&D
○ Generation and characterization of a two-dimensional human intestinal epithelial cell model for evaluation of the absorption rate of orally administered protein/peptide drugs
○ Gene expression analysis: Gene expression of small intestine specific marker and tight junction marker genes
○ Barrier integrity evaluation: TEER measurement
○ Permeability assay to measure protein/peptide drug absorption and sample harvest for absorption rate analysis
Ⅳ. Results
Result
A. Generation and characterization of a two-dimensional human intestinal epithelial cell model for evaluation of the absorption rate of orally administered protein/peptide drugs
○ Generation the two-dimensional human intestinal epithelial progenitor cell differentiation from human pluripotent stem cells by stepwise directed differentiation methods
○ Establishment of mass-production technology through passaging and freezing/thawingof two-dimensional human intestinal epithelial progenitor cells
○ Optimization of functional intestinal epithelial cell differentiation using air liquid interface (AL)I culture technology
B. Gene expression analysis
○ Analyze the expression of small intestine-specific expression markers and tight junction marker genes
○ Analysis of gene expression of specific functional transporters and drug metabolism-related enzymes in a small intestine epithelial model
C. Barrier integrity evaluation
○ Optimizing Transwell culture system to perform permeability assay to measure protein/peptide drug absorption a
○ Cell surface structure analysis using SEM for phenotypic observation of intestinal epithelial model and membrane integrity evaluation through TEER measurement
D. Absorption evaluation and sample harvest for absorption rate analysis
○ Permeability assay to measure protein/peptide drug absorption
○ Sample harvest for absorption rate analysis (819 case)
Ⅴ. Utilization plan of R&D results
○ Evaluation of absorption and metabolism of protein/peptide drug based on human normal intestinal epithelial cell model
○ Increase the efficiency of new protein/peptide drug development; It can be possible to accurately predict the absorption of protein/peptide drug candidates in the preclinical stage, thus increasing the success rate of innovative new protein/peptide drug development
○ Securing competitiveness in peptide/protein pharmaceuticals; By grafting high-functional intestinal epithelial cell model and macromolecular intracellular transport technology, we take technological advantage as a source technology for peptide/protein drug development
