Establishment of SLC15A1/PEPT1-Knockout Human-Induced Pluripotent Stem Cell Line for Intestinal Drug Absorption Studies.
CRISPR-Cas9
PEPT1
SLC15A1
drug absorption
drug transporter
genome editing
human iPS cells
intestinal epithelial-like cells
Journal
Molecular therapy. Methods & clinical development
ISSN: 2329-0501
Titre abrégé: Mol Ther Methods Clin Dev
Pays: United States
ID NLM: 101624857
Informations de publication
Date de publication:
12 Jun 2020
12 Jun 2020
Historique:
received:
26
06
2019
accepted:
11
11
2019
entrez:
1
1
2020
pubmed:
1
1
2020
medline:
1
1
2020
Statut:
epublish
Résumé
Because many peptide and peptide-mimetic drugs are substrates of peptide transporter 1, it is important to evaluate the peptide transporter 1-mediated intestinal absorption of drug candidates in the early phase of drug development. Although intestinal cell lines treated with inhibitors of peptide transporter 1 are widely used to examine whether drug candidates are substrates for peptide transporter 1, these inhibitors are not sufficiently specific for peptide transporter 1. In this study, to generate a more precise evaluation model, we established peptide transporter 1-knockout induced pluripotent stem cells (iPSCs) by using a CRISPR-Cas9 system and differentiated the cells into intestinal epithelial-like cells. The permeability value and uptake capacity of glycylsarcosine (substrate of peptide transporter 1) in peptide transporter 1-knockout intestinal epithelial-like cells were significantly lower than those in wild-type intestinal epithelial-like cells, suggesting that peptide transporter 1 was successfully depleted in the epithelial cells. Taken together, our model can be useful in the development of peptide and peptide-mimetic drugs.
Identifiants
pubmed: 31890740
doi: 10.1016/j.omtm.2019.11.008
pii: S2329-0501(19)30133-0
pmc: PMC6926248
doi:
Types de publication
Journal Article
Langues
eng
Pagination
49-57Informations de copyright
© 2019 The Author(s).
Références
Nature. 2016 May 5;533(7601):125-9
pubmed: 27120160
Drug Metab Dispos. 2012 Jul;40(7):1328-35
pubmed: 22490229
Proc Natl Acad Sci U S A. 2014 Nov 25;111(47):16772-7
pubmed: 25385620
Am J Physiol Gastrointest Liver Physiol. 2015 Feb 1;308(3):G188-97
pubmed: 25394661
Am J Physiol Gastrointest Liver Physiol. 2001 Sep;281(3):G697-704
pubmed: 11518682
Drug Metab Dispos. 2002 May;30(5):541-7
pubmed: 11950785
Mol Pharm. 2008 Nov-Dec;5(6):1122-30
pubmed: 19434858
J Pharm Sci. 2002 Mar;91(3):669-79
pubmed: 11920752
Biochem Biophys Res Commun. 1996 Mar 27;220(3):848-52
pubmed: 8607854
Pharm Res. 1998 Aug;15(8):1154-9
pubmed: 9706043
Molecules. 2008 Feb 18;13(2):412-31
pubmed: 18305428
Nucleic Acids Res. 2017 May 19;45(9):5198-5207
pubmed: 28334759
Am J Physiol. 1985 Aug;249(2 Pt 1):G153-60
pubmed: 2992286
Drug Metab Pharmacokinet. 2014;29(1):44-51
pubmed: 23822979
Pharmacol Toxicol. 2002 Jun;90(6):285-96
pubmed: 12403049
J Pharmacol Exp Ther. 1992 Feb;260(2):482-6
pubmed: 1738097
Biomaterials. 2018 Apr;161:24-32
pubmed: 29421559
J Pharm Sci. 1998 Nov;87(11):1286-91
pubmed: 9811478
Biochem Pharmacol. 2016 May 1;107:81-90
pubmed: 26979860
Drug Metab Dispos. 2013 Jan;41(1):40-9
pubmed: 23011759
Nature. 2017 Nov 23;551(7681):464-471
pubmed: 29160308
Cell Mol Gastroenterol Hepatol. 2019;8(3):513-526
pubmed: 31228606
J Pharmacol Exp Ther. 2006 Feb;316(2):636-46
pubmed: 16258023
Chem Biodivers. 2009 Nov;6(11):2092-100
pubmed: 19937843
Sci Rep. 2015 Nov 12;5:16479
pubmed: 26559489
Pharm Res. 2006 Jun;23(6):1209-16
pubmed: 16729224
Nature. 2016 Apr 20;533(7603):420-4
pubmed: 27096365
Science. 2016 Sep 16;353(6305):
pubmed: 27492474
Drug Metab Dispos. 2015 Apr;43(4):603-10
pubmed: 25650381
Drug Metab Dispos. 2019 Jun;47(6):632-638
pubmed: 30962288
Front Pharmacol. 2013 Jul 08;4:79
pubmed: 23847534
Stem Cells. 2013 Jun;31(6):1086-96
pubmed: 23378042
Biol Pharm Bull. 2018;41(5):697-706
pubmed: 29709907
Drug Metab Dispos. 2009 Jul;37(7):1404-10
pubmed: 19389857
AAPS PharmSci. 2001;3(1):E9
pubmed: 11741260
Stem Cell Reports. 2018 Dec 11;11(6):1539-1550
pubmed: 30472010
Eur J Med Chem. 2018 Aug 5;156:180-189
pubmed: 30006163
J Pharmacol Exp Ther. 2004 Nov;311(2):659-67
pubmed: 15226381
J Pharmacol Exp Ther. 2004 Aug;310(2):437-45
pubmed: 15075386