Title:
GENETICALLY MODIFIED CELL LINES FOR METABOLIC STUDIES
Document Type and Number:
WIPO Patent Application WO/2018/151825
Kind Code:
A3
Abstract:
A cell line includes a genetic modification at a genetic locus that affects metabolism of a drug in a manner similar to a human subject having a genotype that affects metabolism of the drug. A method for making such a cell line generally includes identifying a locus and allelic variants at the locus in a human that affect metabolism of the drug, providing a parental cell line that comprises the locus that affects metabolism of the drug in the human subject, and introducing a genetic modification into the parental cell at the locus, thereby forming a variant cell line comprising an allelic variant at the locus having the genetic modification.
Inventors:
DORR CASEY (US)
ISRANI AJAY (US)
ISRANI AJAY (US)
Application Number:
PCT/US2018/000037
Publication Date:
October 11, 2018
Filing Date:
February 16, 2018
Export Citation:
Assignee:
MINNEAPOLIS MEDICAL RES FOUNDATION (US)
DORR CASEY R (US)
ISRANI AJAY K (US)
DORR CASEY R (US)
ISRANI AJAY K (US)
International Classes:
C40B30/04; C12N15/01; C12N15/52; C12Q1/68; C12Q1/6827; C40B30/06; G01N33/15; G06F19/18
Domestic Patent References:
| WO2012092379A2 | 2012-07-05 | |||
| WO2015081115A1 | 2015-06-04 |
Foreign References:
| US20100311606A1 | 2010-12-09 |
Other References:
PASSEY, C ET AL.: "Dosing equation for tacrolimus using genetic variants and clinical factors", BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, vol. 72, no. 6, December 2011 (2011-12-01), pages 948 - 957, XP055554045
KUEHL, P ET AL.: "Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression", NATURE, vol. 27, no. 4, April 2001 (2001-04-01), pages 383 - 391, XP008040441
GELLNER, K ET AL.: "Genomic organization of the human CYP3A locus: identification of a new, inducible CYP3A gene", PHARMACOGENETICS, vol. 11, no. 2, 1 March 2001 (2001-03-01), pages 111 - 121, XP009005485
DORR, CR ET AL.: "CRISPR/Cas9 genetic modification of CYP3A5 *3 in HuH-7 human 1 hepatocyte cell line leads to cell lines with increased midazolam and tacrolimus metabolism", 7 DRUG METABOLISM & DISPOSITION, vol. 45, no. 8, August 2017 (2017-08-01), pages 957 - 965, XP055554049
LU ET AL.: "CRISPR knockout rat cytochrome P450 3A1/2 model for advancing drug 1 metabolism and pharmacokinetics research", SCIENTIFIC REPORTS, vol. 7, no. 42922, 20 February 2017 (2017-02-20), XP055554052
KUEHL, P ET AL.: "Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression", NATURE, vol. 27, no. 4, April 2001 (2001-04-01), pages 383 - 391, XP008040441
GELLNER, K ET AL.: "Genomic organization of the human CYP3A locus: identification of a new, inducible CYP3A gene", PHARMACOGENETICS, vol. 11, no. 2, 1 March 2001 (2001-03-01), pages 111 - 121, XP009005485
DORR, CR ET AL.: "CRISPR/Cas9 genetic modification of CYP3A5 *3 in HuH-7 human 1 hepatocyte cell line leads to cell lines with increased midazolam and tacrolimus metabolism", 7 DRUG METABOLISM & DISPOSITION, vol. 45, no. 8, August 2017 (2017-08-01), pages 957 - 965, XP055554049
LU ET AL.: "CRISPR knockout rat cytochrome P450 3A1/2 model for advancing drug 1 metabolism and pharmacokinetics research", SCIENTIFIC REPORTS, vol. 7, no. 42922, 20 February 2017 (2017-02-20), XP055554052
Attorney, Agent or Firm:
GRAM, Christopher D. (US)
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