CRISPR-Cas9: A method for establishing rat models of drug metabolism and pharmacokinetics

Autor: Yuanjin Zhang, Yuanqing Guo, Yeye Xu, Jie Liu, Jian Lu, Xin Wang
Jazyk: angličtina
Rok vydání: 2021
Předmět:
NCBI
National Center for Biotechnology Information
TALEN
transcriptional activators like effector nucleases
RNP
ribonucleoprotein
Review
Gene editing
SREBP-2
sterol regulatory element-binding protein 2
0302 clinical medicine
AAV
adeno-associated virus
Genome editing
DDI
drug–drug interaction
CRISPR
General Pharmacology
Toxicology and Pharmaceutics
0303 health sciences
HDR
homology directed repair
tracRNA
trans-activating crRNA
ADMET
absorption
distribution
metabolism
excretion and toxicity
HIV
human immunodeficiency virus
030220 oncology & carcinogenesis
CRISPR-Cas9
OATP1B
organic anion transporting polypeptides 1B
Rat model
CRISPR-Cas
clustered regularly interspaced short palindromic repeats-CRISPR-associated
pre-crRNA
pre-CRISPR RNA
Computational biology
RM1-950
03 medical and health sciences
Animal model
Pharmacokinetics
TALE
transcriptional activator-like effector
ZFN
zinc finger nucleases
DSB
double-strand break
PAM
protospacer-associated motif
Gene knockout
BSEP
bile salt export pump
030304 developmental biology
Drug metabolism
KO
knockout
Mechanism (biology)
sgRNA
single guide RNA
crRNAs
CRISPR RNAs
WT
wild-type
HBV
hepatitis B virus
T7E I
T7 endonuclease I
NHEJ
non-homologous end joining
SD
Sprague–Dawley
OTS
off-target site
DMPK
drug metabolism and pharmacokinetics
Therapeutics. Pharmacology
HPV
human papillomaviruses
Zdroj: Acta Pharmaceutica Sinica B, Vol 11, Iss 10, Pp 2973-2982 (2021)
Acta Pharmaceutica Sinica. B
ISSN: 2211-3835
Popis: The 2020 Nobel Prize in Chemistry recognized CRISPR-Cas9, a super-selective and precise gene editing tool. CRISPR-Cas9 has an obvious advantage in editing multiple genes in the same cell, and presents great potential in disease treatment and animal model construction. In recent years, CRISPR-Cas9 has been used to establish a series of rat models of drug metabolism and pharmacokinetics (DMPK), such as Cyp, Abcb1, Oatp1b2 gene knockout rats. These new rat models are not only widely used in the study of drug metabolism, chemical toxicity, and carcinogenicity, but also promote the study of DMPK related mechanism, and further strengthen the relationship between drug metabolism and pharmacology/toxicology. This review systematically introduces the advantages and disadvantages of CRISPR-Cas9, summarizes the methods of establishing DMPK rat models, discusses the main challenges in this field, and proposes strategies to overcome these problems.
Graphical abstract CRISPR-Cas9 has been applied to construct rat models of drug metabolism and pharmacokinetics (DMPK). These new models are used not only to study drug metabolism and transport, but also to explore the mechanism of DMPK.Image 1
Databáze: OpenAIRE
Externí odkaz: