Applications of Functional Genomics for Drug Discovery

被引：8

作者：

Kabadi, Ami M. ^{[1
]}

McDonnell, Eoin ^{[1
]}

Frank, Christopher L. ^{[1
]}

Drowley, Lauren ^{[2
]}

机构：

[1] Element Genom, Durham, NC USA

[2] UCB Biosci, 701 W Main St, Durham, NC 27701 USA

来源：

SLAS DISCOVERY | 2020年 / 25卷 / 08期

关键词：

gene editing; RNAi; shRNA; CRISPR; epigenetics; genomics; cell-based assays; WIDE CRISPR SCREEN; CONTROLLING GENE-EXPRESSION; SHORT-INTERFERING RNAS; ONE-STEP GENERATION; TRANSCRIPTIONAL REPRESSION; HOMOLOGOUS RECOMBINATION; THERAPEUTIC TARGETS; FUNCTION MUTATIONS; ENDOGENOUS GENES; DNA METHYLATION;

D O I：

10.1177/2472555220902092

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Many diseases, such as diabetes, autoimmune diseases, cancer, and neurological disorders, are caused by a dysregulation of a complex interplay of genes. Genome-wide association studies have identified thousands of disease-linked polymorphisms in the human population. However, detailing the causative gene expression or functional changes underlying those associations has been elusive in many cases. Functional genomics is an emerging field of research that aims to deconvolute the link between genotype and phenotype by making use of large -omic data sets and next-generation gene and epigenome editing tools to perturb genes of interest. Here we review how functional genomic tools can be used to better understand the biological interplay between genes, improve disease modeling, and identify novel drug targets. Incorporation of functional genomic capabilities into conventional drug development pipelines is predicted to expedite the development of first-in-class therapeutics.

引用

页码：823 / 842

页数：20

共 179 条

[1] Step-Wise Chondrogenesis of Human Induced Pluripotent Stem Cells and Purification Via a Reporter Allele Generated by CRISPR-Cas9 Genome Editing [J].

Adkar, Shaunak S. ;

Wu, Chia-Lung ;

Willard, Vincent P. ;

Dicks, Amanda ;

Ettyreddy, Adarsh ;

Steward, Nancy ;

Bhutani, Nidhi ;

Gersbach, Charles A. ;

Guilak, Farshid .

STEM CELLS, 2019, 37 (01) :65-76

[2] Genetic effects on gene expression across human tissues [J].

Aguet, Francois ;

Brown, Andrew A. ;

Castel, Stephane E. ;

Davis, Joe R. ;

He, Yuan ;

Jo, Brian ;

Mohammadi, Pejman ;

Park, Yoson ;

Parsana, Princy ;

Segre, Ayellet V. ;

Strober, Benjamin J. ;

Zappala, Zachary ;

Cummings, Beryl B. ;

Gelfand, Ellen T. ;

Hadley, Kane ;

Huang, Katherine H. ;

Lek, Monkol ;

Li, Xiao ;

Nedzel, Jared L. ;

Nguyen, Duyen Y. ;

Noble, Michael S. ;

Sullivan, Timothy J. ;

Tukiainen, Taru ;

MacArthur, Daniel G. ;

Getz, Gad ;

Management, Nih Program ;

Addington, Anjene ;

Guan, Ping ;

Koester, Susan ;

Little, A. Roger ;

Lockhart, Nicole C. ;

Moore, Helen M. ;

Rao, Abhi ;

Struewing, Jeffery P. ;

Volpi, Simona ;

Collection, Biospecimen ;

Brigham, Lori E. ;

Hasz, Richard ;

Hunter, Marcus ;

Johns, Christopher ;

Johnson, Mark ;

Kopen, Gene ;

Leinweber, William F. ;

Lonsdale, John T. ;

McDonald, Alisa ;

Mestichelli, Bernadette ;

Myer, Kevin ;

Roe, Bryan ;

Salvatore, Michael ;

Shad, Saboor .

NATURE, 2017, 550 (7675) :204-+

[3] Genomic Copy Number Dictates a Gene-Independent Cell Response to CRISPR/Cas9 Targeting [J].

Aguirre, Andrew J. ;

Meyers, Robin M. ;

Weir, Barbara A. ;

Vazquez, Francisca ;

Zhang, Cheng-Zhong ;

Ben-David, Uri ;

Cook, April ;

Ha, Gavin ;

Harrington, William F. ;

Doshi, Mihir B. ;

Kost-Alimova, Maria ;

Gill, Stanley ;

Xu, Han ;

Ali, Levi D. ;

Jiang, Guozhi ;

Pantel, Sasha ;

Lee, Yenarae ;

Goodale, Amy ;

Cherniack, Andrew D. ;

Oh, Coyin ;

Kryukov, Gregory ;

Cowley, Glenn S. ;

Garraway, Levi A. ;

Stegmaier, Kimberly ;

Roberts, Charles W. ;

Golub, Todd R. ;

Meyerson, Matthew ;

Root, David E. ;

Tsherniak, Aviad ;

Hahn, William C. .

CANCER DISCOVERY, 2016, 6 (08) :914-929

[4] A global reference for human genetic variation [J].

Altshuler, David M. ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Donnelly, Peter ;

Eichler, Evan E. ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Green, Eric D. ;

Hurles, Matthew E. ;

Knoppers, Bartha M. ;

Korbel, Jan O. ;

Lander, Eric S. ;

Lee, Charles ;

Lehrach, Hans ;

Mardis, Elaine R. ;

Marth, Gabor T. ;

McVean, Gil A. ;

Nickerson, Deborah A. ;

Wang, Jun ;

Wilson, Richard K. ;

Boerwinkle, Eric ;

Doddapaneni, Harsha ;

Han, Yi ;

Korchina, Viktoriya ;

Kovar, Christie ;

Lee, Sandra ;

Muzny, Donna ;

Reid, Jeffrey G. ;

Zhu, Yiming ;

Chang, Yuqi ;

Feng, Qiang ;

Fang, Xiaodong ;

Guo, Xiaosen ;

Jian, Min ;

Jiang, Hui ;

Jin, Xin ;

Lan, Tianming ;

Li, Guoqing ;

Li, Jingxiang ;

Li, Yingrui ;

Liu, Shengmao ;

Liu, Xiao ;

Lu, Yao ;

Ma, Xuedi ;

Tang, Meifang ;

Wang, Bo .

NATURE, 2015, 526 (7571) :68-+

[5] A Landscape of Therapeutic Cooperativity in KRAS Mutant Cancers Reveals Principles for Controlling Tumor Evolution [J].

Anderson, Grace R. ;

Winter, Peter S. ;

Lin, Kevin H. ;

Nussbaum, Daniel P. ;

Cakir, Merve ;

Stein, Elizabeth M. ;

Soderquist, Ryan S. ;

Crawford, Lorin ;

Leeds, Jim C. ;

Newcomb, Rachel ;

Stepp, Priya ;

Yip, Catherine ;

Wardell, Suzanne E. ;

Tingley, Jennifer P. ;

Ali, Moiez ;

Xu, Mengmeng ;

Ryan, Meagan ;

McCall, Shannon J. ;

McRee, Autumn J. ;

Counter, Christopher M. ;

Der, Channing J. ;

Wood, Kris C. .

CELL REPORTS, 2017, 20 (04) :999-1015

[6] FACS-Assisted CRISPR-Cas9 Genome Editing Facilitates Parkinson's Disease Modeling [J].

Arias-Fuenzalida, Jonathan ;

Jarazo, Javier ;

Qing, Xiaobing ;

Walter, Jonas ;

Gomez-Giro, Gemma ;

Nickels, Sarah Louise ;

Zaehres, Holm ;

Schoeler, Hans Robert ;

Schwamborn, Jens Christian .

STEM CELL REPORTS, 2017, 9 (05) :1423-1431

[7]

Ayer DE, 1996, MOL CELL BIOL, V16, P5772

[8]

Bailey MH, 2018, CELL, V173, P371, DOI [10.1016/j.cell.2018.02.060, 10.1016/j.cell.2018.07.034]

[9] Conditionally Stabilized dCas9 Activator for Controlling Gene Expression in Human Cell Reprogramming and Differentiation [J].

Balboa, Diego ;

Weltner, Jere ;

Eurola, Solja ;

Trokovic, Ras ;

Wartiovaara, Kirmo ;

Otonkoski, Timo .

STEM CELL REPORTS, 2015, 5 (03) :448-459

[10] THE 65-KDA SUBUNIT OF HUMAN NF-KAPPA-B FUNCTIONS AS A POTENT TRANSCRIPTIONAL ACTIVATOR AND A TARGET FOR V-REL-MEDIATED REPRESSION [J].

BALLARD, DW ;

DIXON, EP ;

PEFFER, NJ ;

BOGERD, H ;

DOERRE, S ;

STEIN, B ;

GREENE, WC .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (05) :1875-1879

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