Next Generation Precision Medicine: CRISPR-mediated Genome Editing for the Treatment of Neurodegenerative Disorders

被引：21

作者：

Raikwar, Sudhanshu P. ^{[1
,2
]}

Kikkeri, Nidhi S. ^{[1
]}

Sakuru, Ragha ^{[1
]}

Saeed, Daniyal ^{[1
]}

Zahoor, Haris ^{[1
]}

Premkumar, Keerthivaas ^{[1
]}

Mentor, Shireen ^{[1
,3
]}

Thangavel, Ramasamy ^{[1
,2
]}

Dubova, Iuliia ^{[1
,2
]}

Ahmed, Mohammad Ejaz ^{[1
,2
]}

Selvakumar, Govindhasamy P. ^{[1
,2
]}

Kempuraj, Duraisamy ^{[1
,2
]}

Zaheer, Smita ^{[1
]}

Iyer, Shankar S. ^{[1
,2
]}

Zaheer, Asgar ^{[1
,2
]}

机构：

[1] Univ Missouri, Ctr Translat Neurosci, Sch Med, Dept Neurol, M741A Med Sci Bldg,1 Hosp Dr, Columbia, MO 65211 USA

[2] Harry S Truman Mem Vet Hosp, US Dept Vet Affairs, Columbia, MO 65201 USA

[3] Univ Western Cape, Dept Med Biosci, ZA-7535 Bellville, South Africa

来源：

JOURNAL OF NEUROIMMUNE PHARMACOLOGY | 2019年 / 14卷 / 04期

基金：

美国国家卫生研究院;

关键词：

Alzheimer's disease; Amyotrophic lateral sclerosis; CRISPR; Frontotemporal dementia; genome editing; Huntington's disease; neuroinflammation; neurodegeneration; Parkinson's disease; GLIA MATURATION FACTOR; CONTROL CELL-LINE; IN-UTERO ELECTROPORATION; AMYLOID-BETA DEPOSITION; IPSC-DERIVED NEURONS; ALZHEIMERS-DISEASE; FRONTOTEMPORAL DEMENTIA; GAMMA-SECRETASE; GENE-EXPRESSION; MOUSE MODELS;

D O I：

10.1007/s11481-019-09849-y

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Despite significant advancements in the field of molecular neurobiology especially neuroinflammation and neurodegeneration, the highly complex molecular mechanisms underlying neurodegenerative diseases remain elusive. As a result, the development of the next generation neurotherapeutics has experienced a considerable lag phase. Recent advancements in the field of genome editing offer a new template for dissecting the precise molecular pathways underlying the complex neurodegenerative disorders. We believe that the innovative genome and transcriptome editing strategies offer an excellent opportunity to decipher novel therapeutic targets, develop novel neurodegenerative disease models, develop neuroimaging modalities, develop next-generation diagnostics as well as develop patient-specific precision-targeted personalized therapies to effectively treat neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, Frontotemporal dementia etc. Here, we review the latest developments in the field of CRISPR-mediated genome editing and provide unbiased futuristic insights regarding its translational potential to improve the treatment outcomes andminimize financial burden. However, despite significant advancements, we would caution the scientific community that since the CRISPR field is still evolving, currently we do not know the full spectrum of CRISPR-mediated side effects. In the wake of the recent news regarding CRISPR-edited human babies being born in China, we urge the scientific community to maintain high scientific and ethical standards and utilize CRISPR for developing in vitro disease in a dish model, in vivo testing in nonhuman primates and lower vertebrates and for the development of neurotherapeutics for the currently incurable neurodegenerative disorders.

引用

页码：608 / 641

页数：34

共 318 条

[1] RNA targeting with CRISPR-Cas13 [J].

Abudayyeh, Omar O. ;

Gootenberg, Jonathan S. ;

Essletzbichler, Patrick ;

Han, Shuo ;

Joung, Julia ;

Belanto, Joseph J. ;

Verdine, Vanessa ;

Cox, David B. T. ;

Kellner, Max J. ;

Regev, Aviv ;

Lander, Eric S. ;

Voytas, Daniel F. ;

Ting, Alice Y. ;

Zhang, Feng .

NATURE, 2017, 550 (7675) :280-+

[2] C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector [J].

Abudayyeh, Omar O. ;

Gootenberg, Jonathan S. ;

Konermann, Silvana ;

Joung, Julia ;

Slaymaker, Ian M. ;

Cox, David B. T. ;

Shmakov, Sergey ;

Makarova, Kira S. ;

Semenova, Ekaterina ;

Minakhin, Leonid ;

Severinov, Konstantin ;

Regev, Aviv ;

Lander, Eric S. ;

Koonin, Eugene V. ;

Zhang, Feng .

SCIENCE, 2016, 353 (6299)

[3] Formin 2 links neuropsychiatric phenotypes at young age to an increased risk for dementia [J].

Agis-Balboa, Roberto Carlos ;

Pinheiro, Paulo S. ;

Rebola, Nelson ;

Kerimoglu, Cemil ;

Benito, Eva ;

Gertig, Michael ;

Bahari-Javan, Sanaz ;

Jain, Gaurav ;

Burkhardt, Susanne ;

Delalle, Ivana ;

Jatzko, Alexander ;

Dettenhofer, Markus ;

Zunszain, Patricia A. ;

Schmitt, Andrea ;

Falkai, Peter ;

Pape, Julius C. ;

Binder, Elisabeth B. ;

Mulle, Christophe ;

Fischer, Andre ;

Sananbenesi, Farahnaz .

EMBO JOURNAL, 2017, 36 (19) :2815-2828

[4] Co-Localization of Glia Maturation Factor with NLRP3 Inflammasome and Autophagosome Markers in Human Alzheimer's Disease Brain [J].

Ahmed, Mohammad Ejaz ;

Iyer, Shankar ;

Thangavel, Ramasamy ;

Kempuraj, Duraisamy ;

Selvakumar, Govindhasamy Pushpavathi ;

Raikwar, Sudhanshu P. ;

Zaheer, Smita ;

Zaheer, Asgar .

JOURNAL OF ALZHEIMERS DISEASE, 2017, 60 (03) :1143-1160

[5] Diabetes mellitus and Alzheimer's disease: shared pathology and treatment? [J].

Akter, Kawser ;

Lanza, Emily A. ;

Martin, Stephen A. ;

Myronyuk, Natalie ;

Rua, Melanie ;

Raffa, Robert B. .

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2011, 71 (03) :365-376

[6] Predicting the mutations generated by repair of Cas9-induced double-strand breaks [J].

Allen, Felicity ;

Crepaldi, Luca ;

Alsinet, Clara ;

Strong, Alexander J. ;

Kleshchevnikov, Vitalii ;

De Angeli, Pietro ;

Palenikova, Petra ;

Khodak, Anton ;

Kiselev, Vladimir ;

Kosicki, Michael ;

Bassett, Andrew R. ;

Harding, Heather ;

Galanty, Yaron ;

Munoz-Martinez, Francisco ;

Metzakopian, Emmanouil ;

Jackson, Stephen P. ;

Parts, Leopold .

NATURE BIOTECHNOLOGY, 2019, 37 (01) :64-+

[7] Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells exhibit impaired neurodifferentiation [J].

Allende, Maria L. ;

Cook, Emily K. ;

Larman, Bridget C. ;

Nugent, Adrienne ;

Brady, Jacqueline M. ;

Golebiowski, Diane ;

Sena-Esteves, Miguel ;

Tifft, Cynthia J. ;

Proia, Richard L. .

JOURNAL OF LIPID RESEARCH, 2018, 59 (03) :550-563

[8] ALS-linked FUS mutations confer loss and gain of function in the nucleus by promoting excessive formation of dysfunctional paraspeckles [J].

An, Haiyan ;

Skelt, Lucy ;

Notaro, Antonietta ;

Highley, J. Robin ;

Fox, Archa H. ;

La Bella, Vincenzo ;

Buchman, Vladimir L. ;

Shelkovnikova, Tatyana A. .

ACTA NEUROPATHOLOGICA COMMUNICATIONS, 2019, 7

[9]

[Anonymous], CURR PROTOC NEUROSCI

[10] 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

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