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Aging and disease
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The Impact of CRISPR-Cas9 on Age-related Disorders: From Pathology to Therapy
Allen Caobi1, Rajib Kumar Dutta1, Luis D. Garbinski3, Maria Esteban-Lopez2, Yasemin Ceyhan2, Mickensone Andre1, Marko Manevski1, Chet Raj Ojha1, Jessica Lapierre1, Sneham Tiwari1, Tiyash Parira1, Nazira El-Hage1
1Departments of Immunology and Nano-medicine,
2Human and Molecular Genetics and
3Cell Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, USA.
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With advances in medical technology, the number of people over the age of 60 is on the rise, and thus, increasing the prevalence of age-related pathologies within the aging population. Neurodegenerative disorders, cancers, metabolic and inflammatory diseases are some of the most prevalent age-related pathologies affecting the growing population. It is imperative that a new treatment to combat these pathologies be developed. Although, still in its infancy, the CRISPR-Cas9 system has become a potent gene-editing tool capable of correcting gene-mediated age-related pathology, and therefore ameliorating or eliminating disease symptoms. Deleting target genes using the CRISPR-Cas9 system or correcting for gene mutations may ameliorate many different neurodegenerative disorders detected in the aging population. Cancer cells targeted by the CRISPR-Cas9 system may result in an increased sensitivity to chemotherapeutics, lower proliferation, and higher cancer cell death. Finally, reducing gene targeting inflammatory molecules production through microRNA knockout holds promise as a therapeutic strategy for both arthritis and inflammation. Here we present a review based on how the expanding world of genome editing can be applied to disorders and diseases affecting the aging population.

Keywords gene-editing      aging      CRISPR-Cas9      neurodegeneration      cancer      alternative medicine     
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These authors contributed equally to this work.

Just Accepted Date: 11 October 2019  
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Allen Caobi
Rajib Kumar Dutta
Luis D. Garbinski
Maria Esteban-Lopez
Yasemin Ceyhan
Mickensone Andre
Marko Manevski
Chet Raj Ojha
Jessica Lapierre
Sneham Tiwari
Tiyash Parira
Nazira El-Hage
Cite this article:   
Allen Caobi,Rajib Kumar Dutta,Luis D. Garbinski, et al. The Impact of CRISPR-Cas9 on Age-related Disorders: From Pathology to Therapy[J]. Aging and disease, 10.14336/AD.2019.0927
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Figure 1.  Prevalence of age-associated disorders that can be targeted by the CRISPR-Cas9 technology. Schematic diagram of the health burden associated with increased life expectancy in men (depicted in blue color) and women (depicted in pink color). Neurodegenerative disorders, cancer, metabolic and inflammatory diseases are among the most prevalent age-related pathologies affecting the growing population.
DisordersTarget SitesModelAdvantagesDisadvantagesRefs
Amyotrophic Lateral Sclerosis (ALS)SOD1 and FUSHuman ALS patient fibroblastCorrects the mutation A272C in SOD1 and G1566A in FUS.Not clear if treatment after disease onset would be effective.
Reduces the expression of both wild type and mutant gene.
tardbp and fusZebrafishCorrection of missense mutations in these ALS-associated genes.N/A*(55)

Alzheimer’s Disease (AD)
Mutation in Amyloid Precursor Protein (APP)HumanDisrupts expression of mutant APP.Shortening the gRNA could lead to decreased on-target efficacy(66; 75)
PSEN2Basal forebrain cholinergic neuronsCorrection of the N141I mutation resulted in normalization of observed Aβ42/40 increase.N/A*(73)
PSEN2HumanAbolishes the electrophysiological deficit and restores the number of spikes and spike height.N/A*(73)
PSEN1Human(c.236 T > C) mutation correction.N/A*(71)
PSEN1Human(c.449C > T) mutation correction of the PSEN1 gene.N/A*(72)
APOE4HumanConverts APOE4 to APOE2 or E3.
Effective in neutralizing the risk of AD.

Parkinson’s Disease (PD)
LRRK2HumanCorrects the p.G2019S mutation in LRRK2 and neurite complexity.
Retained pluripotency of hiPSCs after gene editing.
SNCAHuman cell lineCorrects mutation in SNCA gene.N/A*(103)
Colorectal Cancer
PAR3LHuman CaCO-2 CellsKO results in reduced proliferation and induction of apoptosis of CRC cell line.Study was limited to CRC cell lines, no primary cells used.(38)
TP53Human colon adenocarcinoma-derived cell linesCorrection of mutations of TP53 at exon 3 and exon 10 may alter the malignant potential of these cells.Not tested on all of the genomic mutations and clinical varieties of TP53.(131)
APCHuman and mouse organoidsColonoscopy-guided mucosal injection used to deliver CRISPR-engineered organoids.
Facilitates studying adenoma-carcinoma-metastasis progression.
Colonoscopy and specific surgical equipment are required.(139)
KRASHuman cell linessgRNA library targeting protein-coding genes in KRAS-mutant CRC cell lines used to identify genes associated with reduced tumor growth.N/A*(36)

Prostate Cancer
PD-1Phase I clinical trialPD-1 knockdown of T cells in castration-resistant prostate cancer.Confirmation of successful knockdown and a significant change in disease phenotype cannot yet be made, as the clinical trial is ongoing.(152)
GPRC6A Human cell lineReduces primary tumor growth.N/A*(148)
Androgen receptor (AR) geneHuman Cell lineRestrains growth of androgen-dependent prostate cancer and potential therapeutic strategy for prostate cancer treatment.Limited to androgen-dependent prostate cancer not androgen-independent prostate cancer.(146)
Transcription factor NANOG andpseudogene NANOGP8Human cell lineAttenuates malignant potential and migration capability.Knockout of both NANOG1 and NANOGP8 genes is lethal.(150)

Breast Cancer
HER2Human cell lineInhibits cell growth and tumorgenicity.Effects downstream MAPK/ERK and PI3K/AKT signaling cascades, in non-cancer cells.(163)
PtenMouse modelPten silencing by lentiviral delivery results in development of invasive lobular breast cancer.Lentiviral delivery causes immune response.(161)
CDK8/19Human cell lineSuppress estrogen-induced gene expression in breast cancer.N/A*(169)
Ubr5MiceImpairs tumor growth and metastasis.N/A*(170)
MIEN1Human epithelial breast cancerDeletions of MIEN1 gene lead to the abrogation of breast cancer.N/A*(171)
Ovarian CancerDNMT1Human ovarian cancer cell line (SKOV-3) and miceInhibition of tumor growthN/A*(175; 176)
MTH1A subcutaneous xenograft tumor model of SKOV3 cells in BALB/c nude miceApoptosis and genetic damage of cancerous cells resulting in tumor growth inhibition.N/A*(177)
miR-21Human ovarian cancer cell lines (SKOV-3 & OVCAR3)Inhibition of the epithelial-to-mesenchymal transition (EMT) in ovarian cancer cells.N/A*(178)
PARP-1SKOV-3 cell line and a SKOV-3 xenograft BALB/C mice modelIncreased cancer cell deathN/A*(179)
Rheumatoid arthritisFOXP3-associated genesHuman Regulatory T-cell (Treg)Augmentation of the suppressive ability of Tregs via increased Treg stability.
Insertion of chimeric antigen receptor (CAR) gene increased potency in cancer therapy.
Lung infectionMUC18
Human primary airway epithelial cells (AECs)Reduced IL-8 (proinflammatory chemokine) responses.Mixed population of edited cells and phenotypic changes unrelated to the gene knockout.(12)
Table 1  Therapeutic applications of CRISPR-Cas9 system in age-related disorders.
Table 1  includes a list of diseases related to the aging population that the CRISPR technology has been used for. Included in the list are the target sites, models, advantages and obstacles of using CRISPR-Cas9 technology.
Figure 2.  CRISPR-Cas9 system and age-related disorder target genes. Schematic representation of the CRISPR-Cas9 mediated genome editing and potential target genes associated with ALS, AD, PD, HD, cancers and inflammatory disorders. The functional gene may be inserted (green box), the mutated gene may be replaced with a wild-type gene (yellow box) or be removed altogether (red box).
[1] Johnson IP (2015). Age-related neurodegenerative disease research needs aging models. Front Aging Neurosci, 7:168.
[2] Wyss-Coray T (2016). Ageing, neurodegeneration and brain rejuvenation. Nature, 539:180-186.
[3] Pray LA, Institute of Medicine (U.S.). Planning Committee for Food Supply and Aging Populations., National Academies Press (U.S.). 2010. Providing healthy and safe foods as we age : workshop summary. Washington, D.C.: National Academies Press. ix, 181 p. pp.
[4] McGeer PL, McGeer EG (2002). Inflammatory processes in amyotrophic lateral sclerosis. Muscle & Nerve, 26:459-470.
[5] McGeer PL, McGeer EG (2004). Inflammation and neurodegeneration in Parkinson's disease. Parkinsonism & Related Disorders, 10:S3-S7.
[6] McGeer EG, McGeer PL (2003). Inflammatory processes in Alzheimer's disease. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 27:741-749.
[7] Smith BD, Smith GL, Hurria A, Hortobagyi GN, Buchholz TA (2009). Future of Cancer Incidence in the United States: Burdens Upon an Aging, Changing Nation. Journal of Clinical Oncology, 27:2758-2765.
[8] de la Fuente-Nunez C, Lu TK (2017). CRISPR-Cas9 technology: applications in genome engineering, development of sequence-specific antimicrobials, and future prospects. Integr Biol (Camb), 9:109-122.
[9] Hsu PD, Lander ES, Zhang F (2014). Development and applications of CRISPR-Cas9 for genome engineering. Cell, 157:1262-1278.
[10] Berns K, Hijmans EM, Mullenders J, Brummelkamp TR, Velds A, Heimerikx M, et al. (2004). A large-scale RNAi screen in human cells identifies new components of the p53 pathway. Nature, 428:431-437.
[11] Jackson AL, Burchard J, Schelter J, Chau BN, Cleary M, Lim L, et al. (2006). Widespread siRNA "off-target" transcript silencing mediated by seed region sequence complementarity. RNA, 12:1179-1187.
[12] Chu HW, Rios C, Huang C, Wesolowska-Andersen A, Burchard EG, O'Connor BP, et al. (2015). CRISPR-Cas9-mediated gene knockout in primary human airway epithelial cells reveals a proinflammatory role for MUC18. Gene Ther, 22:822-829.
[13] Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E (2012). A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science, 337:816-821.
[14] Li Q, Qin Z, Wang Q, Xu T, Yang Y, He Z (2019). Applications of Genome Editing Technology in Animal Disease Modeling and Gene Therapy. Computational and structural biotechnology journal, 17:689-698.
[15] Lino CA, Harper JC, Carney JP, Timlin JA (2018). Delivering CRISPR: a review of the challenges and approaches. Drug Deliv, 25:1234-1257.
[16] Fan P, He Z-Y, Xu T, Phan K, Chen GG, Wei Y-Q (2018). Exposing cancer with CRISPR-Cas9: from genetic identification to clinical therapy. Translational Cancer Research, 7:817-827.
[17] Barrangou R, Marraffini LA (2014). CRISPR-Cas systems: Prokaryotes upgrade to adaptive immunity. Mol Cell, 54:234-244.
[18] Doudna JA, Charpentier E (2014). Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science, 346:1258096.
[19] He ZY, Men K, Qin Z, Yang Y, Xu T, Wei YQ (2017). Non-viral and viral delivery systems for CRISPR-Cas9 technology in the biomedical field. Sci China Life Sci, 60:458-467.
[20] Rath D, Amlinger L, Rath A, Lundgren M (2015). The CRISPR-Cas immune system: biology, mechanisms and applications. Biochimie, 117:119-128.
[21] Shalem O, Sanjana NE, Zhang F (2015). High-throughput functional genomics using CRISPR-Cas9. Nat Rev Genet, 16:299-311.
[22] Peng R, Lin G, Li J (2016). Potential pitfalls of CRISPR/Cas9-mediated genome editing. FEBS J, 283:1218-1231.
[23] Hille F, Charpentier E (2016). CRISPR-Cas: biology, mechanisms and relevance. Philos Trans R Soc Lond B Biol Sci, 371.
[24] Tsai SQ, Joung JK (2016). Defining and improving the genome-wide specificities of CRISPR-Cas9 nucleases. Nat Rev Genet, 17:300-312.
[25] Mir A, Edraki A, Lee J, Sontheimer EJ (2018). Type II-C CRISPR-Cas9 Biology, Mechanism, and Application. ACS Chem Biol, 13:357-365.
[26] Jiang F, Liu JJ, Osuna BA, Xu M, Berry JD, Rauch BJ, et al. (2019). Temperature-Responsive Competitive Inhibition of CRISPR-Cas9. Mol Cell, 73:601-610 e605.
[27] Jiang F, Doudna JA (2017). CRISPR-Cas9 Structures and Mechanisms. Annu Rev Biophys, 46:505-529.
[28] Nishimasu H, Ran FA, Hsu PD, Konermann S, Shehata SI, Dohmae N, et al. (2014). Crystal structure of Cas9 in complex with guide RNA and target DNA. Cell, 156:935-949.
[29] Deltcheva E, Chylinski K, Sharma CM, Gonzales K, Chao Y, Pirzada ZA, et al. (2011). CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III. Nature, 471:602-607.
[30] Davis L, Maizels N (2014). Homology-directed repair of DNA nicks via pathways distinct from canonical double-strand break repair. Proc Natl Acad Sci U S A, 111:E924-932.
[31] Gilbert LA, Horlbeck MA, Adamson B, Villalta JE, Chen Y, Whitehead EH, et al. (2014). Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation. Cell, 159:647-661.
[32] Gilbert LA, Larson MH, Morsut L, Liu Z, Brar GA, Torres SE, et al. (2013). CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell, 154:442-451.
[33] Cong L, Ran FA, Cox D, Lin SL, Barretto R, Habib N, et al. (2013). Multiplex Genome Engineering Using CRISPR/Cas Systems. Science, 339:819-823.
[34] Mali P, Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE, et al. (2013). RNA-guided human genome engineering via Cas9. Science, 339:823-826.
[35] Hart T, Chandrashekhar M, Aregger M, Steinhart Z, Brown KR, MacLeod G, et al. (2015). High-Resolution CRISPR Screens Reveal Fitness Genes and Genotype-Specific Cancer Liabilities. Cell, 163:1515-1526.
[36] Yau EH, Kummetha IR, Lichinchi G, Tang R, Zhang Y, Rana TM (2017). Genome-Wide CRISPR Screen for Essential Cell Growth Mediators in Mutant KRAS Colorectal Cancers. Cancer Res, 77:6330-6339.
[37] Wanzel M, Vischedyk JB, Gittler MP, Gremke N, Seiz JR, Hefter M, et al. (2016). CRISPR-Cas9-based target validation for p53-reactivating model compounds. Nat Chem Biol, 12:22-28.
[38] Li T, Liu D, Lei X, Jiang Q (2017). Par3L enhances colorectal cancer cell survival by inhibiting Lkb1/AMPK signaling pathway. Biochem Biophys Res Commun, 482:1037-1041.
[39] Drost J, van Boxtel R, Blokzijl F, Mizutani T, Sasaki N, Sasselli V, et al. (2017). Use of CRISPR-modified human stem cell organoids to study the origin of mutational signatures in cancer. Science, 358:234-+.
[40] Kuipers EJ, Grady WM, Lieberman D, Seufferlein T, Sung JJ, Boelens PG, et al. (2015). Colorectal cancer. Nat Rev Dis Primers, 1:15065.
[41] Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F (2013). Genome engineering using the CRISPR-Cas9 system. Nature Protocols, 8:2281-2308.
[42] De Ravin SS, Li L, Wu X, Choi U, Allen C, Koontz S, et al. (2017). CRISPR-Cas9 gene repair of hematopoietic stem cells from patients with X-linked chronic granulomatous disease. Sci Transl Med, 9.
[43] Wu YX, Liang D, Wang YH, Bai MZ, Tang W, Bao SM, et al. (2013). Correction of a Genetic Disease in Mouse via Use of CRISPR-Cas9. Cell Stem Cell, 13:659-662.
[44] Fries JF (2005). The compression of morbidity (Reprinted from the Milbank Memorial Fund Quarterly, vol 61, pg 397-419, 1983). Milbank Quarterly, 83:801-823.
[45] Rodriguez M, Rodriguez-Sabate C, Morales I, Sanchez A, Sabate M (2015). Parkinson's disease as a result of aging. Aging Cell, 14:293-308.
[46] Kramer NJ, Haney MS, Morgens DW, Jovicic A, Couthouis J, Li A, et al. (2018). CRISPR-Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity. Nature Genetics, 50:603-+.
[47] Peters OM, Ghasemi M, Brown RH, Jr. (2015). Emerging mechanisms of molecular pathology in ALS. J Clin Invest, 125:1767-1779.
[48] van Es MA, Hardiman O, Chio A, Al-Chalabi A, Pasterkamp RJ, Veldink JH, et al. (2017). Amyotrophic lateral sclerosis. Lancet, 390:2084-2098.
[49] Broeckhoven KSaCV.2010. CHAPTER 56 - Frontotemporal Dementia. In Brocklehurst's Textbook of Geriatric Medicine and Gerontology. K.R. Howard M. Fillit, and Kenneth Woodhouse, editor: Elsevier. 5.
[50] Yi DS, Bertoux M, Mioshi E, Hodges JR, Hornberger M (2013). Fronto-striatal atrophy correlates of neuropsychiatric dysfunction in frontotemporal dementia (FTD) and Alzheimer's disease (AD). Dement Neuropsychol, 7:75-82.
[51] Wang L, Yi F, Fu L, Yang J, Wang S, Wang Z, et al. (2017). CRISPR/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis patient iPSCs. Protein Cell, 8:365-378.
[52] Kennedy Z, Xue W, Brown R (2017). Postnatal CRISPR-mediated genome editing prolongs survival in a mouse model of amyotrophic lateral sclerosis (S3.003). Neurology, 88:S3.003.
[53] Kruminis-Kaszkiel E, Juranek J, Maksymowicz W, Wojtkiewicz J (2018). CRISPR/Cas9 Technology as an Emerging Tool for Targeting Amyotrophic Lateral Sclerosis (ALS). International Journal of Molecular Sciences, 19.
[54] Tu Z, Yang W, Yan S, Guo X, Li XJ (2015). CRISPR/Cas9: a powerful genetic engineering tool for establishing large animal models of neurodegenerative diseases. Mol Neurodegener, 10:35.
[55] Armstrong GAB, Liao MJ, You ZP, Lissouba A, Chen BE, Drapeau P (2016). Homology Directed Knockin of Point Mutations in the Zebrafish tardbp and fus Genes in ALS Using the CRISPR/Cas9 System. Plos One, 11.
[56] Lin HQ, Hu HJ, Duan WS, Liu YL, Tan GJ, Li ZY, et al. (2018). Intramuscular Delivery of scAAV9-hIGF1 Prolongs Survival in the hSOD1(G93A) ALS Mouse Model via Upregulation of D-Amino Acid Oxidase. Molecular Neurobiology, 55:682-695.
[57] Heidenreich M, Zhang F (2016). Applications of CRISPR-Cas systems in neuroscience. Nature Reviews Neuroscience, 17:36-44.
[58] Heneka MT, O'Banion MK (2007). Inflammatory processes in Alzheimer's disease. Journal of Neuroimmunology, 184:69-91.
[59] Selkoe DJ.2015. Chapter 67 - Alzheimer Disease. In Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease. R.N.R.a.J.M. Pascual, editor: Elsevier. 753-768.
[60] Guzior N, Wieckowska A, Panek D, Malawska B (2015). Recent Development of Multifunctional Agents as Potential Drug Candidates for the Treatment of Alzheimer's Disease. Current Medicinal Chemistry, 22:373-404.
[61] Folch J, Petrov D, Ettcheto M, Abad S, Sanchez-Lopez E, Garcia ML, et al. (2016). Current Research Therapeutic Strategies for Alzheimer's Disease Treatment. Neural Plasticity.
[62] Alzheimer's A (2015). 2015 Alzheimer's disease facts and figures. Alzheimers Dement, 11:332-384.
[63] Prince M Comas-Herrera A., Knapp M., Guerchet M., andKaragiannidou M.2016. World Alzheimer Report 2016: Improving healthcare for people living with dementia coverage, Quality and costs now and in the future. London: Global Observatory for Ageing and Dementia Care and the PSSRU at the London School of Economics and Political Sciences.
[64] Kerchner GAaW-C, T.2016. The Role of Aging in Alzheimer’s Disease. In Advances in Geroscience: Springer.
[65] Bird TD.1993. Early-Onset Familial Alzheimer Disease. In GeneReviews((R)). M.P. Adam, H.H. Ardinger, R.A. Pagon, S.E. Wallace, L.J.H. Bean, K. Stephens, and A. Amemiya, editors. Seattle (WA).
[66] Das U, Scott DA, Ganguly A, Koo EH, Tang Y, Roy S (2013). Activity-induced convergence of APP and BACE-1 in acidic microdomains via an endocytosis-dependent pathway. Neuron, 79:447-460.
[67] Isik AT (2010). Late onset Alzheimer's disease in older people. Clin Interv Aging, 5:307-311.
[68] Rohn TT, Kim N, Isho NF, Mack JM (2018). The Potential of CRISPR/Cas9 Gene Editing as a Treatment Strategy for Alzheimer's Disease. J Alzheimers Dis Parkinsonism, 8.
[69] Cummings JL, Morstorf T, Zhong K (2014). Alzheimer's disease drug-development pipeline: few candidates, frequent failures. Alzheimers Research & Therapy, 6.
[70] Jo A, Ham S, Lee GH, Lee YI, Kim S, Lee YS, et al. (2015). Efficient Mitochondrial Genome Editing by CRISPR/Cas9. Biomed Res Int, 2015:305716.
[71] Pires C, Schmid B, Petraeus C, Poon A, Nimsanor N, Nielsen TT, et al. (2016). Generation of a gene-corrected isogenic control cell line from an Alzheimer's disease patient iPSC line carrying a A79V mutation in PSEN1. Stem Cell Res, 17:285-288.
[72] Poon A, Schmid B, Pires C, Nielsen TT, Hjermind LE, Nielsen JE, et al. (2016). Generation of a gene-corrected isogenic control hiPSC line derived from a familial Alzheimer's disease patient carrying a L150P mutation in presenilin 1. Stem Cell Res, 17:466-469.
[73] Ortiz-Virumbrales M, Moreno CL, Kruglikov I, Marazuela P, Sproul A, Jacob S, et al. (2017). CRISPR/Cas9-Correctable mutation-related molecular and physiological phenotypes in iPSC-derived Alzheimer's PSEN2 (N141I) neurons. Acta Neuropathol Commun, 5:77.
[74] Offen D, Rabinowitz R, Michaelson D, Ben-Zur T (2018). Towards Gene-Editing Treatment for Alzheimer's Disease: Apoe4 Allele-Specific Knockout Using a Crispr Cas9 Variant. Cytotherapy, 20:S18-S18.
[75] Gyorgy B, Ingelsson M, Loov C, Takeda S, Lannfelt L, Hyman BT, et al. (2016). CRISPR-Cas9 Mediated Gene Editing in a Monogenic Form of Alzheimer's Disease. Molecular Therapy, 24:S226-S227.
[76] Gyorgy B, Loov C, Zaborowski MP, Takeda S, Kleinstiver BP, Commins C, et al. (2018). CRISPR/Cas9 Mediated Disruption of the Swedish APP Allele as a Therapeutic Approach for Early-Onset Alzheimer's Disease. Molecular Therapy-Nucleic Acids, 11:429-440.
[77] Murlidharan G, Sakamoto K, Rao L, Corriher T, Wang D, Gao G, et al. (2016). CNS-restricted Transduction and CRISPR/Cas9-mediated Gene Deletion with an Engineered AAV Vector. Mol Ther Nucleic Acids, 5:e338.
[78] Abdullah R, Basak I, Patil KS, Alves G, Larsen JP, Moller SG (2015). Parkinson's disease and age: The obvious but largely unexplored link. Exp Gerontol, 68:33-38.
[79] Winklhofer KF, Haass C (2010). Mitochondrial dysfunction in Parkinson's disease. Biochim Biophys Acta, 1802:29-44.
[80] Hardy J, Lewis P, Revesz T, Lees A, Paisan-Ruiz C (2009). The genetics of Parkinson's syndromes: a critical review. Curr Opin Genet Dev, 19:254-265.
[81] Hindle JV (2010). Ageing, neurodegeneration and Parkinson's disease. Age Ageing, 39:156-161.
[82] Van Den Eeden SK, Tanner CM, Bernstein AL, Fross RD, Leimpeter A, Bloch DA, et al. (2003). Incidence of Parkinson's disease: Variation by age, gender, and Race/Ethnicity. American Journal of Epidemiology, 157:1015-1022.
[83] (NINDS) NIoNDaS.2018. Parkinson’s Disease. In NIH Fact Sheets: National Institutes of Health.
[84] Tysnes O-B, Storstein A (2017). Epidemiology of Parkinson’s disease. Journal of Neural Transmission, 124:901-905.
[85] DeMaagd G, Philip A (2015). Parkinson's Disease and Its Management: Part 1: Disease Entity, Risk Factors, Pathophysiology, Clinical Presentation, and Diagnosis. P & T : a peer-reviewed journal for formulary management, 40:504-532.
[86] Yang WL, Tu ZC, Sun Q, Li XJ (2016). CRISPR/Cas9: Implications for Modeling and Therapy of Neurodegenerative Diseases. Frontiers in Molecular Neuroscience, 9.
[87] Klein C, Westenberger A (2012). Genetics of Parkinson's disease. Cold Spring Harbor perspectives in medicine, 2:a008888-a008888.
[88] Moon HE, Paek SH (2015). Mitochondrial Dysfunction in Parkinson's Disease. Exp Neurobiol, 24:103-116.
[89] Bose A, Beal MF (2016). Mitochondrial dysfunction in Parkinson's disease. J Neurochem, 139 Suppl 1:216-231.
[90] Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, et al. (1998). Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature, 392:605-608.
[91] Potting C, Crochemore C, Moretti F, Nigsch F, Schmidt I, Manneville C, et al. (2018). Genome-wide CRISPR screen for PARKIN regulators reveals transcriptional repression as a determinant of mitophagy. Proceedings of the National Academy of Sciences of the United States of America, 115:E180-E189.
[92] Finkel T (2011). Telomeres and mitochondrial function. Circ Res, 108:903-904.
[93] Arnold AS, Egger A, Handschin C (2011). PGC-1alpha and myokines in the aging muscle - a mini-review. Gerontology, 57:37-43.
[94] Scheffold A, Holtman IR, Dieni S, Brouwer N, Katz SF, Jebaraj BM, et al. (2016). Telomere shortening leads to an acceleration of synucleinopathy and impaired microglia response in a genetic mouse model. Acta Neuropathol Commun, 4:87.
[95] Maiti P, Manna J, Dunbar GL (2017). Current understanding of the molecular mechanisms in Parkinson's disease: Targets for potential treatments. Transl Neurodegener, 6:28.
[96] Xi LH, Schmidt JC, Zaug AJ, Ascarrunz DR, Cech TR (2015). A novel two-step genome editing strategy with CRISPR-Cas9 provides new insights into telomerase action and TERT gene expression. Genome Biology, 16.
[97] Choudhury SR, Hudry E, Maguire CA, Sena-Esteves M, Breakefield XO, Grandi P (2017). Viral vectors for therapy of neurologic diseases. Neuropharmacology, 120:63-80.
[98] Kaplitt MG, Feigin A, Tang C, Fitzsimons HL, Mattis P, Lawlor PA, et al. (2007). Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: an open label, phase I trial. Lancet, 369:2097-2105.
[99] Christine CW, Starr PA, Larson PS, Eberling JL, Jagust WJ, Hawkins RA, et al. (2009). Safety and tolerability of putaminal AADC gene therapy for Parkinson disease. Neurology, 73:1662-1669.
[100] Gasmi M, Herzog CD, Brandon EP, Cunningham JJ, Ramirez GA, Ketchum ET, et al. (2007). Striatal delivery of neurturin by CERE-120, an AAV2 vector for the treatment of dopaminergic neuron degeneration in Parkinson's disease. Mol Ther, 15:62-68.
[101] Zharikov AD, Cannon JR, Tapias V, Bai Q, Horowitz MP, Shah V, et al. (2015). shRNA targeting alpha-synuclein prevents neurodegeneration in a Parkinson's disease model. J Clin Invest, 125:2721-2735.
[102] Qing X, Walter J, Jarazo J, Arias-Fuenzalida J, Hillje AL, Schwamborn JC (2017). CRISPR/Cas9 and piggyBac-mediated footprint-free LRRK2-G2019S knock-in reveals neuronal complexity phenotypes and alpha-Synuclein modulation in dopaminergic neurons. Stem Cell Res, 24:44-50.
[103] Arias-Fuenzalida J, Jarazo J, Qing X, Walter J, Gomez-Giro G, Nickels SL, et al. (2017). FACS-Assisted CRISPR-Cas9 Genome Editing Facilitates Parkinson's Disease Modeling. Stem Cell Reports, 9:1423-1431.
[104] Guerreiro R, Ross OA, Kun-Rodrigues C, Hernandez DG, Orme T, Eicher JD, et al. (2018). Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study. Lancet Neurol, 17:64-74.
[105] Walker Z, Possin KL, Boeve BF, Aarsland D (2015). Lewy body dementias. Lancet, 386:1683-1697.
[106] Wilson RS, Boyle PA, Yu L, Segawa E, Sytsma J, Bennett DA (2015). Conscientiousness, dementia related pathology, and trajectories of cognitive aging. Psychol Aging, 30:74-82.
[107] Kaneko H, Kakita A, Kasuga K, Nozaki H, Ishikawa A, Miyashita A, et al. (2007). Enhanced accumulation of phosphorylated alpha-synuclein and elevated beta-amyloid 42/40 ratio caused by expression of the presenilin-1 deltaT440 mutant associated with familial Lewy body disease and variant Alzheimer's disease. J Neurosci, 27:13092-13097.
[108] Hashimoto M, Rockenstein E, Mante M, Crews L, Bar-On P, Gage FH, et al. (2004). An antiaggregation gene therapy strategy for Lewy body disease utilizing beta-synuclein lentivirus in a transgenic model. Gene Ther, 11:1713-1723.
[109] Lewis J, Melrose H, Bumcrot D, Hope A, Zehr C, Lincoln S, et al. (2008). In vivo silencing of alpha-synuclein using naked siRNA. Mol Neurodegener, 3:19.
[110] McCormack AL, Mak SK, Henderson JM, Bumcrot D, Farrer MJ, Di Monte DA (2010). Alpha-synuclein suppression by targeted small interfering RNA in the primate substantia nigra. PLoS One, 5:e12122.
[111] Gusella JF, Wexler NS, Conneally PM, Naylor SL, Anderson MA, Tanzi RE, et al. (1983). A polymorphic DNA marker genetically linked to Huntington's disease. Nature, 306:234-238.
[112] Horvath S, Langfelder P, Kwak S, Aaronson J, Rosinski J, Vogt TF, et al. (2016). Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels. Aging (Albany NY), 8:1485-1512.
[113] Myers RH (2004). Huntington's disease genetics. NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics, 1:255-262.
[114] Aylward EH, Harrington DL, Mills JA, Nopoulos PC, Ross CA, Long JD, et al. (2013). Regional atrophy associated with cognitive and motor function in prodromal Huntington disease. J Huntingtons Dis, 2:477-489.
[115] Landles C, Bates GP (2004). Huntingtin and the molecular pathogenesis of Huntington's disease. Fourth in molecular medicine review series. EMBO Rep, 5:958-963.
[116] Rubinsztein DC, Marino G, Kroemer G (2011). Autophagy and aging. Cell, 146:682-695.
[117] Low P (2011). The role of ubiquitin-proteasome system in ageing. Gen Comp Endocrinol, 172:39-43.
[118] Ravikumar B, Vacher C, Berger Z, Davies JE, Luo S, Oroz LG, et al. (2004). Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet, 36:585-595.
[119] Bence NF, Sampat RM, Kopito RR (2001). Impairment of the ubiquitin-proteasome system by protein aggregation. Science, 292:1552-1555.
[120] Monteys AM, Ebanks SA, Keiser MS, Davidson BL (2017). CRISPR/Cas9 Editing of the Mutant Huntingtin Allele In Vitro and In Vivo. Mol Ther, 25:12-23.
[121] Yamamoto A, Lucas JJ, Hen R (2000). Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease. Cell, 101:57-66.
[122] Wild EJ, Tabrizi SJ (2017). Therapies targeting DNA and RNA in Huntington's disease. Lancet Neurol, 16:837-847.
[123] Ghosh R, Tabrizi SJ (2017). Gene suppression approaches to neurodegeneration. Alzheimer's research & therapy, 9:82-82.
[124] Hanahan D, Weinberg RA (2011). Hallmarks of cancer: the next generation. Cell, 144:646-674.
[125] Gustavsson B, Carlsson G, Machover D, Petrelli N, Roth A, Schmoll HJ, et al. (2015). A review of the evolution of systemic chemotherapy in the management of colorectal cancer. Clin Colorectal Cancer, 14:1-10.
[126] Miller JC, Tan S, Qiao G, Barlow KA, Wang J, Xia DF, et al. (2011). A TALE nuclease architecture for efficient genome editing. Nat Biotechnol, 29:143-148.
[127] Bibikova M, Beumer K, Trautman JK, Carroll D (2003). Enhancing gene targeting with designed zinc finger nucleases. Science, 300:764.
[128] Smithies O, Gregg RG, Boggs SS, Koralewski MA, Kucherlapati RS (1985). Insertion of DNA sequences into the human chromosomal beta-globin locus by homologous recombination. Nature, 317:230-234.
[129] Giaever G, Chu AM, Ni L, Connelly C, Riles L, Veronneau S, et al. (2002). Functional profiling of the Saccharomyces cerevisiae genome. Nature, 418:387-391.
[130] Tong AH, Lesage G, Bader GD, Ding H, Xu H, Xin X, et al. (2004). Global mapping of the yeast genetic interaction network. Science, 303:808-813.
[131] Watanabe S, Tsuchiya K, Nishimura R, Shirasaki T, Katsukura N, Hibiya S, et al. (2019). TP53 Mutation by CRISPR System Enhances the Malignant Potential of Colon Cancer. Mol Cancer Res.
[132] Yao W, King DA, Beckwith SL, Gowans GJ, Yen K, Zhou C, et al. (2016). The INO80 Complex Requires the Arp5-Ies6 Subcomplex for Chromatin Remodeling and Metabolic Regulation. Mol Cell Biol, 36:979-991.
[133] Huo Y, Macara IG (2014). The Par3-like polarity protein Par3L is essential for mammary stem cell maintenance. Nat Cell Biol, 16:529-537.
[134] Oliner JD, Kinzler KW, Meltzer PS, George DL, Vogelstein B (1992). Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature, 358:80-83.
[135] Pant V, Lozano G (2014). Limiting the power of p53 through the ubiquitin proteasome pathway. Genes & development, 28:1739-1751.
[136] Issaeva N, Bozko P, Enge M, Protopopova M, Verhoef LG, Masucci M, et al. (2004). Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors. Nat Med, 10:1321-1328.
[137] Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, et al. (2004). In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science, 303:844-848.
[138] Kussie PH, Gorina S, Marechal V, Elenbaas B, Moreau J, Levine AJ, et al. (1996). Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science, 274:948-953.
[139] Roper J, Tammela T, Akkad A, Almeqdadi M, Santos SB, Jacks T, et al. (2018). Colonoscopy-based colorectal cancer modeling in mice with CRISPR-Cas9 genome editing and organoid transplantation. Nat Protoc, 13:217-234.
[140] Jemal A, Center MM, DeSantis C, Ward EM (2010). Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev, 19:1893-1907.
[141] Mathers MJ, Degener S, Sperling H, Roth S (2017). Hematospermia-a Symptom With Many Possible Causes. Deutsches Arzteblatt international, 114:186-191.
[142] Chen F-Z, Zhao X-K (2013). Prostate cancer: current treatment and prevention strategies. Iranian Red Crescent medical journal, 15:279-284.
[143] Tan MH, Li J, Xu HE, Melcher K, Yong EL (2015). Androgen receptor: structure, role in prostate cancer and drug discovery. Acta Pharmacol Sin, 36:3-23.
[144] Davey RA, Grossmann M (2016). Androgen Receptor Structure, Function and Biology: From Bench to Bedside. Clin Biochem Rev, 37:3-15.
[145] Culig Z, Santer FR (2014). Androgen receptor signaling in prostate cancer. Cancer Metastasis Rev, 33:413-427.
[146] Wei C, Wang F, Liu W, Zhao W, Yang Y, Li K, et al. (2018). CRISPR/Cas9 targeting of the androgen receptor suppresses the growth of LNCaP human prostate cancer cells. Mol Med Rep, 17:2901-2906.
[147] Pi M, Quarles LD (2012). GPRC6A regulates prostate cancer progression. Prostate, 72:399-409.
[148] Ye R, Pi M, Cox JV, Nishimoto SK, Quarles LD (2017). CRISPR/Cas9 targeting of GPRC6A suppresses prostate cancer tumorigenesis in a human xenograft model. J Exp Clin Cancer Res, 36:90.
[149] Kregel S, Szmulewitz RZ, Vander Griend DJ (2014). The pluripotency factor Nanog is directly upregulated by the androgen receptor in prostate cancer cells. Prostate, 74:1530-1543.
[150] Kawamura N, Nimura K, Nagano H, Yamaguchi S, Nonomura N, Kaneda Y (2015). CRISPR/Cas9-mediated gene knockout of NANOG and NANOGP8 decreases the malignant potential of prostate cancer cells. Oncotarget, 6:22361-22374.
[151] Zenzmaier C, Sampson N, Plas E, Berger P (2013). Dickkopf-related protein 3 promotes pathogenic stromal remodeling in benign prostatic hyperplasia and prostate cancer. Prostate, 73:1441-1452.
[152] Yi L, Li J (2016). CRISPR-Cas9 therapeutics in cancer: promising strategies and present challenges. Biochim Biophys Acta, 1866:197-207.
[153] Kardooni H, Gonzalez-Gualda E, Stylianakis E, Saffaran S, Waxman J, Kypta RM (2018). CRISPR-Mediated Reactivation of DKK3 Expression Attenuates TGF-beta Signaling in Prostate Cancer. Cancers(Basel), 10.
[154] Sun Y-S, Zhao Z, Yang Z-N, Xu F, Lu H-J, Zhu Z-Y, et al. (2017). Risk Factors and Preventions of Breast Cancer. International journal of biological sciences, 13:1387-1397.
[155] 2017. Breast Cancer Facts & Figures2017-2018. Atlanta.
[156] Onitilo AA, Engel JM, Greenlee RT, Mukesh BN (2009). Breast cancer subtypes based on ER/PR and Her2 expression: comparison of clinicopathologic features and survival. Clin Med Res, 7:4-13.
[157] Prat A, Karginova O, Parker JS, Fan C, He X, Bixby L, et al. (2013). Characterization of cell lines derived from breast cancers and normal mammary tissues for the study of the intrinsic molecular subtypes. Breast Cancer Res Treat, 142:237-255.
[158] White MK, Khalili K (2016). CRISPR/Cas9 and cancer targets: future possibilities and present challenges. Oncotarget, 7:12305-12317.
[159] Yang H, Jaeger M, Walker A, Wei D, Leiker K, Weitao T (2018). Break Breast Cancer Addiction by CRISPR/Cas9 Genome Editing. J Cancer, 9:219-231.
[160] Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, et al. (2007). Patterns of somatic mutation in human cancer genomes. Nature, 446:153-158.
[161] Annunziato S, Kas SM, Nethe M, Yucel H, Del Bravo J, Pritchard C, et al. (2016). Modeling invasive lobular breast carcinoma by CRISPR/Cas9-mediated somatic genome editing of the mammary gland. Genes Dev, 30:1470-1480.
[162] Tosatto A, Sommaggio R, Kummerow C, Bentham RB, Blacker TS, Berecz T, et al. (2016). The mitochondrial calcium uniporter regulates breast cancer progression via HIF-1alpha. EMBO Mol Med, 8:569-585.
[163] Wang H, Sun W (2017). CRISPR-mediated targeting of HER2 inhibits cell proliferation through a dominant negative mutation. Cancer Lett, 385:137-143.
[164] Ell B, Kang Y (2013). Transcriptional control of cancer metastasis. Trends in cell biology, 23:603-611.
[165] Liu Y, Liu Y, Huang R, Song W, Wang J, Xiao Z, et al. (2019). Dependency of the Cancer-Specific Transcriptional Regulation Circuitry on the Promoter DNA Methylome. Cell Rep, 26:3461-3474 e3465.
[166] Maturi V, Moren A, Enroth S, Heldin CH, Moustakas A (2018). Genomewide binding of transcription factor Snail1 in triple-negative breast cancer cells. Mol Oncol, 12:1153-1174.
[167] Wang Y, Zhang T, Kwiatkowski N, Abraham BJ, Lee TI, Xie S, et al. (2015). CDK7-dependent transcriptional addiction in triple-negative breast cancer. Cell, 163:174-186.
[168] Ward E, Vareslija D, Charmsaz S, Fagan A, Browne AL, Cosgrove N, et al. (2018). Epigenome-wide SRC-1-Mediated Gene Silencing Represses Cellular Differentiation in Advanced Breast Cancer. Clin Cancer Res, 24:3692-3703.
[169] McDermott MS, Chumanevich AA, Lim CU, Liang J, Chen M, Altilia S, et al. (2017). Inhibition of CDK8 mediator kinase suppresses estrogen dependent transcription and the growth of estrogen receptor positive breast cancer. Oncotarget, 8:12558-12575.
[170] Liao L, Song M, Li X, Tang L, Zhang T, Zhang L, et al. (2017). E3 Ubiquitin Ligase UBR5 Drives the Growth and Metastasis of Triple-Negative Breast Cancer. Cancer Res, 77:2090-2101.
[171] Van Treuren T, Vishwanatha JK (2018). CRISPR deletion of MIEN1 in breast cancer cells. PLoS One, 13:e0204976.
[172] Choudhury SR, Cui Y, Lubecka K, Stefanska B, Irudayaraj J (2016). CRISPR-dCas9 mediated TET1 targeting for selective DNA demethylation at BRCA1 promoter. Oncotarget, 7:46545-46556.
[173] Reid BM, Permuth JB, Sellers TA (2017). Epidemiology of ovarian cancer: a review. Cancer biology & medicine, 14:9-32.
[174] Aunoble B, Sanches R, Didier E, Bignon YJ (2000). Major oncogenes and tumor suppressor genes involved in epithelial ovarian cancer (review). Int J Oncol, 16:567-576.
[175] He ZY, Zhang YG, Yang YH, Ma CC, Wang P, Du W, et al. (2018). In Vivo Ovarian Cancer Gene Therapy Using CRISPR-Cas9. Human Gene Therapy, 29:223-233.
[176] Yao S, He Z, Chen C (2015). CRISPR/Cas9-Mediated Genome Editing of Epigenetic Factors for Cancer Therapy. Hum Gene Ther, 26:463-471.
[177] Li L, Song L, Liu X, Yang X, Li X, He T, et al. (2019). Correction to Artificial Virus Delivers CRISPR-Cas9 System for Genome Editing of Cells in Mice. ACS Nano, 13:9693.
[178] Huo W, Zhao G, Yin J, Ouyang X, Wang Y, Yang C, et al. (2017). Lentiviral CRISPR/Cas9 vector mediated miR-21 gene editing inhibits the epithelial to mesenchymal transition in ovarian cancer cells. J Cancer, 8:57-64.
[179] Kim SM, Yang Y, Oh SJ, Hong Y, Seo M, Jang M (2017). Cancer-derived exosomes as a delivery platform of CRISPR/Cas9 confer cancer cell tropism-dependent targeting. Journal of Controlled Release, 266:8-16.
[180] Bharat A, Xie F, Baddley JW, Beukelman T, Chen L, Calabrese L, et al. (2012). Incidence and risk factors for progressive multifocal leukoencephalopathy among patients with selected rheumatic diseases. Arthritis care & research, 64:612-615.
[181] Safari F, Farajnia S, Arya M, Zarredar H, Nasrolahi A (2018). CRISPR and personalized Treg therapy: new insights into the treatment of rheumatoid arthritis. Immunopharmacol Immunotoxicol, 40:201-211.
[182] Radhakrishnan S, Otte J, Enam S, Del Valle L, Khalili K, Gordon J (2003). JC virus-induced changes in cellular gene expression in primary human astrocytes. J Virol, 77:10638-10644.
[183] van Schaardenburg D, Breedveld FC (1994). Elderly-onset rheumatoid arthritis. Semin Arthritis Rheum, 23:367-378.
[184] Soubrier M, Mathieu S, Payet S, Dubost JJ, Ristori JM (2010). Elderly-onset rheumatoid arthritis. Joint Bone Spine, 77:290-296.
[185] Wollebo HS, Bellizzi A, Kaminski R, Hu W, White MK, Khalili K (2015). CRISPR/Cas9 System as an Agent for Eliminating Polyomavirus JC Infection. PLoS One, 10:e0136046.
[186] Jing W, Zhang X, Sun W, Hou X, Yao Z, Zhu Y (2015). CRISPR/CAS9-Mediated Genome Editing of miRNA-155 Inhibits Proinflammatory Cytokine Production by RAW264.7 Cells. Biomed Res Int, 2015:326042.
[187] Salvaggio JE (1994). Inhaled particles and respiratory disease. J Allergy Clin Immunol, 94:304-309.
[188] Iwasaki A, Foxman EF, Molony RD (2017). Early local immune defences in the respiratory tract. Nat Rev Immunol, 17:7-20.
[189] Wang T, Wei JJ, Sabatini DM, Lander ES (2014). Genetic screens in human cells using the CRISPR-Cas9 system. Science, 343:80-84.
[190] Shalem O, Sanjana NE, Hartenian E, Shi X, Scott DA, Mikkelson T, et al. (2014). Genome-scale CRISPR-Cas9 knockout screening in human cells. Science, 343:84-87.
[191] van Diemen FR, Lebbink RJ (2017). CRISPR/Cas9, a powerful tool to target human herpesviruses. Cell Microbiol, 19.
[192] Lin Y, Wu J, Gu W, Huang Y, Tong Z, Huang L, et al. (2018). Exosome-Liposome Hybrid Nanoparticles Deliver CRISPR/Cas9 System in MSCs. Adv Sci (Weinh), 5:1700611.
[193] Tycko J, Myer VE, Hsu PD (2016). Methods for Optimizing CRISPR-Cas9 Genome Editing Specificity. Molecular cell, 63:355-370.
[194] Elaswad A, Khalil K, Ye Z, Liu Z, Liu S, Peatman E, et al. (2018). Effects of CRISPR/Cas9 dosage on TICAM1 and RBL gene mutation rate, embryonic development, hatchability and fry survival in channel catfish. Sci Rep, 8:16499.
[195] Long C, Amoasii L, Mireault AA, McAnally JR, Li H, Sanchez-Ortiz E, et al. (2016). Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy. Science, 351:400-403.
[196] Brunger JM, Zutshi A, Willard VP, Gersbach CA, Guilak F (2017). CRISPR/Cas9 Editing of Murine Induced Pluripotent Stem Cells for Engineering Inflammation-Resistant Tissues. Arthritis & rheumatology (Hoboken, N.J.), 69:1111-1121.
[197] Jao LE, Wente SR, Chen W (2013). Efficient multiplex biallelic zebrafish genome editing using a CRISPR nuclease system. Proc Natl Acad Sci U S A, 110:13904-13909.
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