CRISPR Gene Therapy: Applications, Limitations, and Implications for the Future

A series of recent discoveries harnessing the adaptive immune system of prokaryotes to perform targeted genome editing is having a transformative influence across the biological sciences. The discovery of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas)...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:Frontiers in oncology Ročník 10; s. 1387
Hlavní autoři: Uddin, Fathema, Rudin, Charles M., Sen, Triparna
Médium: Journal Article
Jazyk:angličtina
Vydáno: Switzerland Frontiers Media S.A 07.08.2020
Témata:
clinical trial
CRISPR/Cas9
ethics
gene therapy
homology-directed repair (HDR)
non-homologous end joining (NHEJ)
Oncology
clinical trial
gene therapy
homology-directed repair (HDR)
CRISPR/Cas9
ethics
non-homologous end joining (NHEJ)
ISSN:2234-943X, 2234-943X
On-line přístup:Získat plný text
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Abstract A series of recent discoveries harnessing the adaptive immune system of prokaryotes to perform targeted genome editing is having a transformative influence across the biological sciences. The discovery of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas) proteins has expanded the applications of genetic research in thousands of laboratories across the globe and is redefining our approach to gene therapy. Traditional gene therapy has raised some concerns, as its reliance on viral vector delivery of therapeutic transgenes can cause both insertional oncogenesis and immunogenic toxicity. While viral vectors remain a key delivery vehicle, CRISPR technology provides a relatively simple and efficient alternative for site-specific gene editing, obliviating some concerns raised by traditional gene therapy. Although it has apparent advantages, CRISPR/Cas9 brings its own set of limitations which must be addressed for safe and efficient clinical translation. This review focuses on the evolution of gene therapy and the role of CRISPR in shifting the gene therapy paradigm. We review the emerging data of recent gene therapy trials and consider the best strategy to move forward with this powerful but still relatively new technology.
AbstractList A series of recent discoveries harnessing the adaptive immune system of prokaryotes to perform targeted genome editing is having a transformative influence across the biological sciences. The discovery of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas) proteins has expanded the applications of genetic research in thousands of laboratories across the globe and is redefining our approach to gene therapy. Traditional gene therapy has raised some concerns, as its reliance on viral vector delivery of therapeutic transgenes can cause both insertional oncogenesis and immunogenic toxicity. While viral vectors remain a key delivery vehicle, CRISPR technology provides a relatively simple and efficient alternative for site-specific gene editing, obliviating some concerns raised by traditional gene therapy. Although it has apparent advantages, CRISPR/Cas9 brings its own set of limitations which must be addressed for safe and efficient clinical translation. This review focuses on the evolution of gene therapy and the role of CRISPR in shifting the gene therapy paradigm. We review the emerging data of recent gene therapy trials and consider the best strategy to move forward with this powerful but still relatively new technology.
A series of recent discoveries harnessing the adaptive immune system of prokaryotes to perform targeted genome editing is having a transformative influence across the biological sciences. The discovery of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas) proteins has expanded the applications of genetic research in thousands of laboratories across the globe and is redefining our approach to gene therapy. Traditional gene therapy has raised some concerns, as its reliance on viral vector delivery of therapeutic transgenes can cause both insertional oncogenesis and immunogenic toxicity. While viral vectors remain a key delivery vehicle, CRISPR technology provides a relatively simple and efficient alternative for site-specific gene editing, obliviating some concerns raised by traditional gene therapy. Although it has apparent advantages, CRISPR/Cas9 brings its own set of limitations which must be addressed for safe and efficient clinical translation. This review focuses on the evolution of gene therapy and the role of CRISPR in shifting the gene therapy paradigm. We review the emerging data of recent gene therapy trials and consider the best strategy to move forward with this powerful but still relatively new technology.A series of recent discoveries harnessing the adaptive immune system of prokaryotes to perform targeted genome editing is having a transformative influence across the biological sciences. The discovery of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas) proteins has expanded the applications of genetic research in thousands of laboratories across the globe and is redefining our approach to gene therapy. Traditional gene therapy has raised some concerns, as its reliance on viral vector delivery of therapeutic transgenes can cause both insertional oncogenesis and immunogenic toxicity. While viral vectors remain a key delivery vehicle, CRISPR technology provides a relatively simple and efficient alternative for site-specific gene editing, obliviating some concerns raised by traditional gene therapy. Although it has apparent advantages, CRISPR/Cas9 brings its own set of limitations which must be addressed for safe and efficient clinical translation. This review focuses on the evolution of gene therapy and the role of CRISPR in shifting the gene therapy paradigm. We review the emerging data of recent gene therapy trials and consider the best strategy to move forward with this powerful but still relatively new technology.
Author Sen, Triparna
Uddin, Fathema
Rudin, Charles M.
AuthorAffiliation 1 Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center , New York, NY , United States
2 Weill Cornell Medicine, Cornell University , New York, NY , United States
AuthorAffiliation_xml – name: 2 Weill Cornell Medicine, Cornell University , New York, NY , United States
– name: 1 Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center , New York, NY , United States
Author_xml – sequence: 1
  givenname: Fathema
  surname: Uddin
  fullname: Uddin, Fathema
– sequence: 2
  givenname: Charles M.
  surname: Rudin
  fullname: Rudin, Charles M.
– sequence: 3
  givenname: Triparna
  surname: Sen
  fullname: Sen, Triparna
BackLink https://www.ncbi.nlm.nih.gov/pubmed/32850447$$D View this record in MEDLINE/PubMed
BookMark eNp1kc9rFDEUx4NUbK09e5M5euhu8zszHoSy2LqwUKkVvIVs8tJNmZmMyYzQ_95sd1tbwVySl_f9fl7C9y066GMPCL0neM5Y3Zz52Ns5xRTPMWG1eoWOKGV81nD28-DZ-RCd5HyHy5ICE8zeoENGa4E5V0foanG9_P7turqEHqqbDSQz3H-qzoehDdaMIfb5tFqFLoyPheldtez-tisfUzVuoLqYxinBO_TamzbDyX4_Rj8uvtwsvs5WV5fLxflqZgUV40xJ3DhquMVCMMka7z04yplUa-IdcUY0RJoGKHWESYyJE1LWSoFx3Fow7Bgtd1wXzZ0eUuhMutfRBP1wEdOtNmkMtgUtHWCggI1QwAmxpm4Ky3nrwVsB68L6vGMN07oDZ6Efk2lfQF92-rDRt_G3VpwqSWUBfNwDUvw1QR51F7KFtjU9xCnr8jFVc45pU6Qfns96GvKYSBGc7QQ2xZwT-CcJwXobu97Grrex64fYi0P847D7uMpjQ_tf3x-HJ7Jb
CitedBy_id crossref_primary_10_1016_j_cell_2023_03_035
crossref_primary_10_1016_j_ijbiomac_2023_124582
crossref_primary_10_1097_GCO_0000000000001022
crossref_primary_10_7759_cureus_79372
crossref_primary_10_1016_j_ejphar_2024_177067
crossref_primary_10_1016_j_blre_2024_101185
crossref_primary_10_1089_crispr_2023_0078
crossref_primary_10_1007_s10142_024_01404_0
crossref_primary_10_1016_j_foohum_2025_100679
crossref_primary_10_1155_2022_1015996
crossref_primary_10_1007_s12672_022_00509_x
crossref_primary_10_1016_j_biochi_2021_12_012
crossref_primary_10_1080_14712598_2024_2405568
crossref_primary_10_3390_cells14120903
crossref_primary_10_1016_j_ejcb_2023_151299
crossref_primary_10_1016_j_biomaterials_2022_121876
crossref_primary_10_3390_brainsci11081081
crossref_primary_10_1016_j_mattod_2025_06_034
crossref_primary_10_2174_0113816128267417231127070901
crossref_primary_10_3389_fncel_2020_631802
crossref_primary_10_3389_fphar_2023_1245809
crossref_primary_10_1186_s12985_024_02286_1
crossref_primary_10_1016_j_omtn_2025_102691
crossref_primary_10_1073_pnas_2212255120
crossref_primary_10_3389_fpubh_2024_1382996
crossref_primary_10_3233_JND_221528
crossref_primary_10_3390_ijms24054341
crossref_primary_10_1016_j_foohum_2023_10_014
crossref_primary_10_3390_pathogens12010056
crossref_primary_10_1016_j_heliyon_2024_e34692
crossref_primary_10_1371_journal_pone_0289863
crossref_primary_10_3389_fgene_2024_1434002
crossref_primary_10_3390_ani13010087
crossref_primary_10_1186_s13014_022_02184_2
crossref_primary_10_1016_j_compbiomed_2022_106348
crossref_primary_10_3390_ijms26083645
crossref_primary_10_3390_nano13111782
crossref_primary_10_3390_biomedicines13071590
crossref_primary_10_1016_j_cels_2025_101299
crossref_primary_10_1080_1061186X_2025_2544786
crossref_primary_10_1038_s44318_024_00158_6
crossref_primary_10_1038_s41467_024_54463_z
crossref_primary_10_1111_fare_13097
crossref_primary_10_1016_j_drudis_2025_104453
crossref_primary_10_1038_s41591_022_02184_5
crossref_primary_10_1002_anie_202217089
crossref_primary_10_1097_ICO_0000000000002857
crossref_primary_10_3390_molecules27031114
crossref_primary_10_7759_cureus_35774
crossref_primary_10_1039_D2BM01005D
crossref_primary_10_3389_fchem_2023_1259435
crossref_primary_10_1016_j_jtha_2023_12_005
crossref_primary_10_3390_v16101641
crossref_primary_10_1007_s13346_024_01754_z
crossref_primary_10_1016_S1773_035X_23_00024_2
crossref_primary_10_1038_s41587_023_01679_x
crossref_primary_10_1093_nar_gkaf887
crossref_primary_10_1038_s41598_023_45964_w
crossref_primary_10_1016_j_hpj_2024_02_012
crossref_primary_10_3390_neuroglia6010009
crossref_primary_10_1007_s12010_023_04708_2
crossref_primary_10_1007_s12032_022_01930_6
crossref_primary_10_1016_j_ijbiomac_2024_131802
crossref_primary_10_1038_s41417_023_00597_z
crossref_primary_10_1089_crispr_2023_0048
crossref_primary_10_1016_j_biopha_2024_116275
crossref_primary_10_1007_s10142_024_01455_3
crossref_primary_10_3390_biomedicines12010238
crossref_primary_10_3390_ijms252212346
crossref_primary_10_3989_scimar_05327_066
crossref_primary_10_1017_pcm_2023_4
crossref_primary_10_3389_fgene_2021_733048
crossref_primary_10_1093_cei_uxae004
crossref_primary_10_1038_s42003_024_06848_5
crossref_primary_10_3389_fcvm_2021_783072
crossref_primary_10_3389_fimmu_2021_747357
crossref_primary_10_1038_s41598_022_11808_2
crossref_primary_10_1242_dmm_052300
crossref_primary_10_1016_j_ymthe_2023_02_009
crossref_primary_10_1038_s41467_024_49343_5
crossref_primary_10_1016_j_tins_2023_02_005
crossref_primary_10_3390_biologics4020010
crossref_primary_10_3389_fgeed_2022_937879
crossref_primary_10_3892_ijo_2025_5729
crossref_primary_10_35118_apjmbb_2025_033_3_07
crossref_primary_10_3390_cells14020131
crossref_primary_10_1007_s12602_025_10561_y
crossref_primary_10_1016_j_microc_2024_112638
crossref_primary_10_3390_ijms22062937
crossref_primary_10_1007_s13402_025_01056_7
crossref_primary_10_1016_j_actbio_2024_10_030
crossref_primary_10_1016_j_trac_2023_117215
crossref_primary_10_1590_0001_3765202320220629
crossref_primary_10_58803_jlar_v4i2_66
crossref_primary_10_1080_17410541_2025_2515002
crossref_primary_10_3389_fgeed_2024_1342193
crossref_primary_10_3390_biom14050511
crossref_primary_10_1007_s00203_025_04360_w
crossref_primary_10_1093_humrep_dead167
crossref_primary_10_7759_cureus_49000
crossref_primary_10_1186_s12859_022_04753_4
crossref_primary_10_3390_cells11172665
crossref_primary_10_1186_s12951_024_02901_x
crossref_primary_10_1016_j_omtn_2025_102666
crossref_primary_10_3390_ijms26146950
crossref_primary_10_3390_genes12050723
crossref_primary_10_3390_ijms242317121
crossref_primary_10_1002_adtp_202500077
crossref_primary_10_1186_s43141_021_00225_z
crossref_primary_10_3390_microorganisms13030599
crossref_primary_10_1016_j_jdrv_2025_05_001
crossref_primary_10_1016_j_engmic_2023_100123
crossref_primary_10_1016_S0929_693X_23_00225_7
crossref_primary_10_3389_fgeed_2022_892769
crossref_primary_10_2147_IJN_S453566
crossref_primary_10_1016_j_jddst_2024_105338
crossref_primary_10_1093_nar_gkae148
crossref_primary_10_3389_fmicb_2022_964848
crossref_primary_10_3390_biomedicines10102445
crossref_primary_10_3389_feduc_2023_1154609
crossref_primary_10_1007_s11357_024_01144_w
crossref_primary_10_3390_audiolres13060083
crossref_primary_10_1126_scitranslmed_adq2005
crossref_primary_10_3390_cancers14122855
crossref_primary_10_3389_fimmu_2022_966084
crossref_primary_10_1016_j_omto_2023_100733
crossref_primary_10_1002_smtd_202401733
crossref_primary_10_1093_lifemedi_lnac054
crossref_primary_10_1016_j_ijbiomac_2025_142987
crossref_primary_10_1016_j_ymgme_2022_08_008
crossref_primary_10_3389_fgeed_2023_1272687
crossref_primary_10_1016_j_omtn_2024_102274
crossref_primary_10_1002_jgm_3726
crossref_primary_10_1016_j_jddst_2024_105546
crossref_primary_10_3390_metabo11120857
crossref_primary_10_3390_ijms222010985
crossref_primary_10_1186_s13287_024_04023_5
crossref_primary_10_2174_0115665232305409240918040639
crossref_primary_10_2174_0115733947290474240315062214
crossref_primary_10_1080_14712598_2022_2154601
crossref_primary_10_1126_sciimmunol_adi0042
crossref_primary_10_1016_j_biopha_2022_113324
crossref_primary_10_1016_j_ymthe_2022_04_020
crossref_primary_10_3389_fimmu_2025_1633845
crossref_primary_10_1038_s41596_022_00721_7
crossref_primary_10_3390_ijms242316933
crossref_primary_10_1080_21655979_2022_2162667
crossref_primary_10_1016_j_retram_2025_103531
crossref_primary_10_3390_jcdd12080281
crossref_primary_10_3389_fchem_2022_957572
crossref_primary_10_3390_biomedicines11123333
crossref_primary_10_3390_ijms241713202
crossref_primary_10_1016_j_pbi_2024_102669
crossref_primary_10_1016_j_coi_2025_102611
crossref_primary_10_1016_j_lfs_2023_122003
crossref_primary_10_1080_17435889_2024_2440307
crossref_primary_10_1016_j_bbrep_2025_102037
crossref_primary_10_1016_j_chembiol_2024_05_005
crossref_primary_10_3390_bioengineering11020179
crossref_primary_10_1038_s41568_022_00441_w
crossref_primary_10_3390_biom12111621
crossref_primary_10_1093_jambio_lxad137
crossref_primary_10_1093_lifemedi_lnad042
crossref_primary_10_1016_j_prp_2024_155509
crossref_primary_10_1002_cmdc_202300359
crossref_primary_10_1016_j_cis_2024_103232
crossref_primary_10_1111_febs_16771
crossref_primary_10_3389_fmicb_2021_784949
crossref_primary_10_3390_ijms25095023
crossref_primary_10_1016_j_jddst_2025_107131
crossref_primary_10_1007_s11274_024_04103_x
crossref_primary_10_1007_s12288_025_02105_9
crossref_primary_10_1007_s40259_024_00647_4
crossref_primary_10_1097_MS9_0000000000003170
crossref_primary_10_1111_imr_13305
crossref_primary_10_25259_ijmr_1716_22
crossref_primary_10_3390_biomedicines11082227
crossref_primary_10_1007_s12291_024_01242_8
crossref_primary_10_3390_antiox14070781
crossref_primary_10_1007_s42823_023_00655_4
crossref_primary_10_1016_j_medp_2024_100027
crossref_primary_10_4103_jpbs_jpbs_583_25
crossref_primary_10_3389_fbioe_2022_833833
crossref_primary_10_1007_s12033_021_00411_x
crossref_primary_10_1007_s12033_021_00418_4
crossref_primary_10_1088_2632_959X_add7f5
crossref_primary_10_1016_j_omtn_2025_102634
crossref_primary_10_1016_j_virol_2024_110160
crossref_primary_10_1007_s00018_020_03725_2
crossref_primary_10_3390_ijms22094590
crossref_primary_10_1016_j_xphs_2024_05_018
crossref_primary_10_1186_s12943_022_01550_8
crossref_primary_10_1002_bit_28603
crossref_primary_10_1093_bjd_ljad321
crossref_primary_10_1016_j_beha_2025_101631
crossref_primary_10_1089_crispr_2022_0084
crossref_primary_10_1016_j_arr_2023_102114
crossref_primary_10_1080_07391102_2023_2227720
crossref_primary_10_3389_fbioe_2022_895713
crossref_primary_10_1016_j_talanta_2022_123780
crossref_primary_10_1016_j_virol_2024_110033
crossref_primary_10_1016_j_drudis_2021_08_013
crossref_primary_10_1016_j_omtn_2023_102035
crossref_primary_10_1016_j_neuron_2023_04_021
crossref_primary_10_1016_j_mattod_2023_04_011
crossref_primary_10_1186_s12985_025_02783_x
crossref_primary_10_1016_j_drudis_2022_103375
crossref_primary_10_1016_j_jse_2022_07_004
crossref_primary_10_1186_s12929_021_00772_0
crossref_primary_10_31083_j_fbl2901041
crossref_primary_10_1186_s40779_020_00292_2
crossref_primary_10_3390_genes13040656
crossref_primary_10_1016_j_cobme_2023_100469
crossref_primary_10_3390_cells10050969
crossref_primary_10_1186_s11658_022_00348_2
crossref_primary_10_1186_s40364_024_00701_x
crossref_primary_10_1016_j_omtn_2025_102640
crossref_primary_10_1038_s41582_022_00751_5
crossref_primary_10_1002_anr3_12210
crossref_primary_10_1016_j_bioelechem_2022_108268
crossref_primary_10_1038_s41574_022_00716_0
crossref_primary_10_1371_journal_pone_0325330
crossref_primary_10_1186_s12951_024_02648_5
crossref_primary_10_1016_j_jconrel_2021_01_014
crossref_primary_10_1080_17460441_2023_2200245
crossref_primary_10_1038_s41585_021_00543_4
crossref_primary_10_1016_j_crmeth_2021_100125
crossref_primary_10_1089_crispr_2021_0148
crossref_primary_10_1093_hmg_ddac208
crossref_primary_10_1016_j_drudis_2021_11_005
crossref_primary_10_1093_procel_pwad013
crossref_primary_10_3390_biom13050788
crossref_primary_10_7759_cureus_67078
crossref_primary_10_1016_j_thromres_2024_04_031
crossref_primary_10_3390_life11111255
crossref_primary_10_3390_ph17070887
crossref_primary_10_1007_s12032_023_02201_8
crossref_primary_10_1002_ange_202217089
crossref_primary_10_1007_s13562_022_00811_3
crossref_primary_10_1016_j_arr_2025_102851
crossref_primary_10_1080_21645515_2025_2488074
crossref_primary_10_1016_j_dscb_2025_100202
crossref_primary_10_1038_s41434_023_00386_1
crossref_primary_10_1016_j_nexres_2025_100276
crossref_primary_10_1111_bcp_15343
crossref_primary_10_1242_dmm_050623
crossref_primary_10_3390_biology13030187
crossref_primary_10_1080_14712598_2022_2049229
crossref_primary_10_1007_s12033_022_00550_9
crossref_primary_10_1016_j_ajpath_2025_02_008
crossref_primary_10_1016_j_ijpharm_2024_123864
crossref_primary_10_1038_s41467_025_59653_x
crossref_primary_10_1007_s43441_025_00807_w
crossref_primary_10_1007_s13346_023_01320_z
crossref_primary_10_1016_j_fgb_2025_104006
crossref_primary_10_1016_j_synbio_2025_03_011
crossref_primary_10_1002_term_3349
crossref_primary_10_3390_pharmaceutics17070903
crossref_primary_10_1016_j_lfs_2025_123756
crossref_primary_10_1016_j_nantod_2025_102740
crossref_primary_10_3390_ph14050417
crossref_primary_10_1016_j_bbagrm_2024_195063
crossref_primary_10_1039_D4NA01004C
crossref_primary_10_3390_cimb47040268
crossref_primary_10_1016_j_trac_2022_116539
crossref_primary_10_1016_j_forsciint_2022_111274
crossref_primary_10_2147_VMRR_S366533
crossref_primary_10_1002_mds_28819
crossref_primary_10_1093_stmcls_sxac074
crossref_primary_10_1039_D4BM00286E
crossref_primary_10_1080_03036758_2024_2347968
crossref_primary_10_1007_s13205_021_02928_z
crossref_primary_10_3389_fonc_2022_960340
crossref_primary_10_1134_S0006297924604672
crossref_primary_10_1016_j_omtn_2022_08_002
crossref_primary_10_3390_cells10020342
crossref_primary_10_7759_cureus_69835
crossref_primary_10_4254_wjh_v17_i6_106573
crossref_primary_10_1186_s11658_023_00464_7
crossref_primary_10_1208_s12249_024_03010_6
crossref_primary_10_1016_j_ijbiomac_2022_11_018
crossref_primary_10_1016_j_xpro_2025_103982
crossref_primary_10_1111_nyas_14936
crossref_primary_10_1007_s40883_024_00338_0
crossref_primary_10_1002_nano_202400015
crossref_primary_10_1016_j_biopha_2021_111917
crossref_primary_10_1002_adma_202504509
crossref_primary_10_2174_0113816128298080240328053845
crossref_primary_10_1007_s12033_024_01125_6
crossref_primary_10_1016_j_bioadv_2025_214471
crossref_primary_10_2174_0113892029361490250310041259
crossref_primary_10_15252_embr_202153902
crossref_primary_10_1039_D3NR06642H
crossref_primary_10_1007_s10238_025_01771_3
crossref_primary_10_1016_j_jddst_2022_103737
crossref_primary_10_3389_fbioe_2023_1138596
crossref_primary_10_3390_jcm12227185
crossref_primary_10_3390_pharmaceutics15041178
crossref_primary_10_1002_adbi_202300679
crossref_primary_10_1089_ars_2022_0180
crossref_primary_10_1186_s40164_024_00570_y
crossref_primary_10_1016_j_jconrel_2024_11_008
Cites_doi 10.1093/bib/bbx001
10.1038/s42003-019-0745-3
10.1186/s13073-015-0215-6
10.1101/2020.04.05.20053355
10.1038/s41551-019-0431-2
10.1038/nature16526
10.1093/jlb/lsz010
10.1016/j.cell.2013.08.021
10.1038/nbt.2647
10.1038/s41591-018-0050-6
10.1016/j.omtn.2018.12.003
10.1016/j.meegid.2020.104384
10.1126/science.270.5235.475
10.1101/gr.171322.113
10.1016/bs.mcb.2016.03.004
10.1056/NEJM199008303230904
10.1038/s41578-019-0145-9
10.1038/s41591-018-0327-9
10.1038/s41586-019-1711-4
10.1146/annurev-physiol-021909-135833
10.1038/nature09886
10.1038/s41591-018-0326-x
10.1097/COH.0b013e328324bbec
10.1038/nature23305
10.1038/s41589-020-0490-4
10.1126/sciadv.aay6812
10.2174/1566523217666171121165935
10.1038/mt.2010.228
10.1016/j.ymgme.2003.08.016
10.1126/science.aay9569
10.1038/s41576-018-0059-1
10.3389/fonc.2019.00297
10.1038/mtna.2015.37
10.1073/pnas.1104144108
10.1182/blood-2011-03-325258
10.1111/nyas.13024
10.1146/annurev-genet-051710-150955
10.3109/10409238.2012.658112
10.1038/nmeth.2857
10.1007/s12539-018-0298-z
10.1016/j.celrep.2016.01.019
10.1126/science.aba8853
10.1016/j.cell.2020.04.020
10.1155/2014/612823
10.1038/nbt.4192
10.1111/j.1365-2958.1993.tb01721.x
10.1038/nature26155
10.1038/s41587-020-0513-4
10.1021/jacs.8b13144
10.1038/nature13769
10.1042/BCJ20170793
10.1186/2052-8426-2-27
10.1126/science.1088547
10.1038/nmeth.4681
10.1038/gt.2009.148
10.1080/10717544.2018.1474964
10.7554/eLife.32724
10.3390/v3060677
10.1016/j.jmb.2015.10.014
10.1089/hum.2015.084
10.3390/ijms20153623
10.1099/mic.0.28048-0
10.1038/s41591-018-0049-z
10.1126/science.288.5466.669
10.1148/radiol.2020200432
10.1126/science.1225829
10.1126/science.1079512
10.1038/srep19675
10.1007/978-1-4939-1862-1_10
10.1038/ncomms12642
10.1038/nbt.3481
10.1089/hum.2016.107
10.1007/978-1-59745-194-9_6
10.1016/j.cell.2018.02.033
10.1038/nbt.2808
10.1016/j.biocel.2018.04.011
10.1038/s41551-019-0505-1
10.1038/s41467-018-05477-x
10.1016/j.jmb.2018.06.037
10.1073/pnas.1906843116
10.1038/s41467-019-09006-2
10.1038/sj.gt.3302243
10.7554/eLife.04766.010
10.1126/science.1159689
10.1038/nbt.3190
10.1038/s41392-019-0044-y
10.1038/mt.2016.5
10.12688/f1000research.11243.1
10.1016/j.ijantimicag.2020.105955
10.1038/nature24268
10.1188/16.ONF.694-696
10.1046/j.1365-2958.2000.01838.x
10.1002/jgm.3107
10.1038/s41467-020-15021-5
10.1172/JCI81163
10.1126/science.aas9129
10.7860/JCDR/2015/10443.5394
10.1016/j.neuron.2017.10.004
10.1126/science.aad5227
10.1073/pnas.1407473111
10.1016/j.gendis.2017.04.001
10.1038/s41591-018-0137-0
10.1038/nmeth.2812
10.1126/science.1231143
10.1126/sciadv.aau0766
10.1186/s13059-017-1318-8
10.1016/j.molcel.2016.02.020
10.1038/nbt.4066
10.1126/sciadv.aaz0051
10.1089/10430349950016852
10.1038/nbt.3404
10.1002/stem.2935
10.1126/science.270.5235.470
10.1021/acs.accounts.9b00106
10.1093/bioinformatics/btaa041
ContentType Journal Article
Copyright Copyright © 2020 Uddin, Rudin and Sen.
Copyright © 2020 Uddin, Rudin and Sen. 2020 Uddin, Rudin and Sen
Copyright_xml – notice: Copyright © 2020 Uddin, Rudin and Sen.
– notice: Copyright © 2020 Uddin, Rudin and Sen. 2020 Uddin, Rudin and Sen
DBID AAYXX
CITATION
NPM
7X8
5PM
DOA
DOI 10.3389/fonc.2020.01387
DatabaseName CrossRef
PubMed
MEDLINE - Academic
PubMed Central (Full Participant titles)
DOAJ Directory of Open Access Journals
DatabaseTitle CrossRef
PubMed
MEDLINE - Academic
DatabaseTitleList
PubMed

MEDLINE - Academic
Database_xml – sequence: 1
  dbid: DOA
  name: DOAJ Directory of Open Access Journals
  url: https://www.doaj.org/
  sourceTypes: Open Website
– sequence: 2
  dbid: NPM
  name: PubMed
  url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 3
  dbid: 7X8
  name: MEDLINE - Academic
  url: https://search.proquest.com/medline
  sourceTypes: Aggregation Database
DeliveryMethod fulltext_linktorsrc
Discipline Medicine
EISSN 2234-943X
ExternalDocumentID oai_doaj_org_article_6de0e2e0a57e411ca89668dfcfefc5eb
PMC7427626
32850447
10_3389_fonc_2020_01387
Genre Journal Article
Review
GrantInformation_xml – fundername: NCI NIH HHS
  grantid: P30 CA008748
– fundername: NCI NIH HHS
  grantid: R01 CA197936
– fundername: NCI NIH HHS
  grantid: U24 CA213274
GroupedDBID 53G
5VS
9T4
AAFWJ
AAKDD
AAYXX
ACGFO
ACGFS
ADBBV
ADRAZ
AFPKN
ALMA_UNASSIGNED_HOLDINGS
AOIJS
BAWUL
BCNDV
CITATION
DIK
EBS
EJD
EMOBN
GROUPED_DOAJ
GX1
HYE
KQ8
M48
M~E
OK1
PGMZT
RNS
RPM
ACXDI
IPNFZ
NPM
RIG
7X8
5PM
ID FETCH-LOGICAL-c525t-7609d2a4c0553639fffed24367b1fd1da5916a9e22d136001d566877ead4ccea3
IEDL.DBID DOA
ISICitedReferencesCount 363
ISICitedReferencesURI http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000563457500001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN 2234-943X
IngestDate Fri Oct 03 12:44:21 EDT 2025
Thu Aug 21 14:12:15 EDT 2025
Fri Sep 05 13:18:39 EDT 2025
Mon Jul 21 05:51:30 EDT 2025
Sat Nov 29 01:49:25 EST 2025
Tue Nov 18 20:27:50 EST 2025
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Keywords clinical trial
gene therapy
homology-directed repair (HDR)
CRISPR/Cas9
ethics
non-homologous end joining (NHEJ)
Language English
License Copyright © 2020 Uddin, Rudin and Sen.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c525t-7609d2a4c0553639fffed24367b1fd1da5916a9e22d136001d566877ead4ccea3
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
ObjectType-Review-3
content type line 23
Lead Contact
This article was submitted to Cancer Genetics, a section of the journal Frontiers in Oncology
Edited by: Israel Gomy, Dana–Farber Cancer Institute, United States
Reviewed by: Nan Wu, Peking Union Medical College Hospital (CAMS), China; Tanja Kunej, University of Ljubljana, Slovenia; Martin Roffe, A.C. Camargo Cancer Center, Brazil
OpenAccessLink https://doaj.org/article/6de0e2e0a57e411ca89668dfcfefc5eb
PMID 32850447
PQID 2437844029
PQPubID 23479
ParticipantIDs doaj_primary_oai_doaj_org_article_6de0e2e0a57e411ca89668dfcfefc5eb
pubmedcentral_primary_oai_pubmedcentral_nih_gov_7427626
proquest_miscellaneous_2437844029
pubmed_primary_32850447
crossref_primary_10_3389_fonc_2020_01387
crossref_citationtrail_10_3389_fonc_2020_01387
PublicationCentury 2000
PublicationDate 2020-08-07
PublicationDateYYYYMMDD 2020-08-07
PublicationDate_xml – month: 08
  year: 2020
  text: 2020-08-07
  day: 07
PublicationDecade 2020
PublicationPlace Switzerland
PublicationPlace_xml – name: Switzerland
PublicationTitle Frontiers in oncology
PublicationTitleAlternate Front Oncol
PublicationYear 2020
Publisher Frontiers Media S.A
Publisher_xml – name: Frontiers Media S.A
References B20
O' Connell (B64) 2014; 516
Hacein-Bey-Abina (B12) 2003; 302
Ma (B112) 2014; 548
Jinek (B28) 2012; 337
Chandrasegaran (B22) 2016; 428
Basak (B104) 2016; 1368
Broughton (B118) 2020; 38
Mojica (B24) 2000; 36
Kleinstiver (B33) 2015; 33
Lee (B89) 2020; 3
Cavazzana-Calvo (B10) 2000; 288
Hiranniramol (B60) 2020; 36
Lino (B61) 2018; 25
Zhai (B114) 2020; 55
Vakulskas (B39) 2018; 24
Humbert (B1) 2012; 47
Luan (B51) 2019; 141
Ablain (B100) 2016; 135
Heigwer (B57) 2014; 11
Moreno (B76) 2019; 3
Hu (B68) 2014; 2014
Tong (B102) 2019; 4
Haapaniemi (B70) 2018; 24
Tan (B50) 2019; 116
Hu (B43) 2018; 556
Bolotin (B25) 2005; 151
Lomova (B85) 2019; 37
Brouns (B26) 2008; 321
Lin (B82) 2014; 3
Walton (B47) 2020; 368
Prakash (B3) 2016; 24
Cong (B30) 2015; 1239
Wyvekens (B42) 2015; 26
Kim (B63) 2020; 4
Rosenberg (B4) 1990; 323
Casini (B38) 2018; 36
Pankowicz (B99) 2016; 7
Strutt (B65) 2018; 7
Sadelain (B17) 2004; 11
Robert (B79) 2015; 7
Xu (B74) 2019; 431
Amer (B2) 2014; 2
Lee (B15) 2017; 4
Nayak (B18) 2010; 17
Maetzig (B13) 2011; 3
Abbott (B119) 2020; 181
Lau (B62) 2017; 6
Konermann (B66) 2018; 173
Nunes (B9) 1999; 10
Chatterjee (B52) 2018; 4
Semenova (B53) 2011; 108
Cohen (B109) 2019
Xin (B88) 2019; 4
Ye (B108) 2014; 111
B106
Blaese (B5) 1995; 270
Deltcheva (B27) 2011; 471
Wilbie (B93) 2019; 52
Moses (B73) 2019; 14
Greely (B110) 2019; 6
Ran (B32) 2013; 154
Zhang (B98) 2020; 6
Goswami (B16) 2019; 9
Fang (B116) 2020
Kulcsár (B37) 2017; 18
Liu (B54) 2016; 6
Richardson (B80) 2016; 34
Hammer (B14) 2016; 43
Anzalone (B91) 2019; 576
Kleinstiver (B35) 2016; 529
Lee (B46) 2018; 9
Ihry (B69) 2018; 24
B115
Shen (B41) 2014; 11
Herzog (B11) 2010; 18
Eid (B87) 2018; 475
Alkhatib (B111) 2009; 4
Nishiyama (B83) 2017; 96
Komarova (B101) 2010; 72
Yu (B96) 2016; 27
Charlesworth (B75) 2019; 25
Yan (B58) 2017; 15
Hui (B94) 2008
Bruegmann (B55) 2019; 20
Fu (B56) 2014; 32
Cullot (B72) 2019; 10
Larochelle (B67) 2018; 15
Chen (B45) 2017; 550
Ling (B86) 2020; 6
Gutschner (B84) 2016; 14
Raper (B8) 2003; 80
Zhang (B31) 2015; 4
Akinsheye (B103) 2011; 118
Nishimasu (B44) 2018; 361
Li (B77) 2018; 99
Maeder (B107) 2019; 25
Kim (B95) 2014; 24
Kosicki (B71) 2018; 36
Kulcsár (B48) 2020; 11
Basak (B105) 2015; 125
Heyer (B81) 2010; 44
Sironi (B113) 2020; 84
Xu (B92) 2019; 21
Anders (B34) 2016; 61
Rees (B90) 2018; 19
Wikramaratna (B117) 2020
Sibbald (B7) 2001; 164
Bibikova (B21) 2003; 300
Cong (B29) 2013; 339
Baylis (B97) 2017; 17
Hsu (B40) 2013; 31
Bordignon (B6) 1995; 270
Ramamoorth (B19) 2015; 9
Bratovič (B49) 2020; 16
Slaymaker (B36) 2016; 351
Mojica (B23) 1993; 9
Maruyama (B78) 2015; 33
Cui (B59) 2018; 10
References_xml – volume: 15
  start-page: 1
  year: 2017
  ident: B58
  article-title: Benchmarking CRISPR on-target sgRNA and design
  publication-title: Brief Bioinform.
  doi: 10.1093/bib/bbx001
– volume: 3
  start-page: 19
  year: 2020
  ident: B89
  article-title: Cytosine base editor 4 but not adenine base editor generates off-target mutations in mouse embryos
  publication-title: Commun Biol.
  doi: 10.1038/s42003-019-0745-3
– volume: 7
  start-page: 93
  year: 2015
  ident: B79
  article-title: Pharmacological inhibition of DNA-PK stimulates Cas9-mediated genome editing
  publication-title: Genome Med.
  doi: 10.1186/s13073-015-0215-6
– year: 2020
  ident: B117
  article-title: Estimating false-negative detection rate of SARS-CoV-2 by RT-PCR
  publication-title: BMJ
  doi: 10.1101/2020.04.05.20053355
– volume: 3
  start-page: 806
  year: 2019
  ident: B76
  article-title: Immune-orthogonal orthologues of AAV capsids and of Cas9 circumvent the immune response to the administration of gene therapy
  publication-title: Nat Biomed Eng.
  doi: 10.1038/s41551-019-0431-2
– volume: 529
  start-page: 490
  year: 2016
  ident: B35
  article-title: High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects
  publication-title: Nature.
  doi: 10.1038/nature16526
– volume: 6
  start-page: 111
  year: 2019
  ident: B110
  article-title: CRISPR'd babies: human germline genome editing in the 'He Jiankui affair'
  publication-title: J Law Biosci.
  doi: 10.1093/jlb/lsz010
– volume: 154
  start-page: 1380
  year: 2013
  ident: B32
  article-title: Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity
  publication-title: Cell.
  doi: 10.1016/j.cell.2013.08.021
– volume: 31
  start-page: 827
  year: 2013
  ident: B40
  article-title: DNA targeting specificity of RNA-guided Cas9 nucleases
  publication-title: Nat Biotechnol.
  doi: 10.1038/nbt.2647
– volume: 24
  start-page: 939
  year: 2018
  ident: B69
  article-title: p53 inhibits CRISPR–Cas9 engineering in human pluripotent stem cells
  publication-title: Nat Med.
  doi: 10.1038/s41591-018-0050-6
– volume: 14
  start-page: 287
  year: 2019
  ident: B73
  article-title: Activating PTEN tumor suppressor expression with the CRISPR/dCas9 system
  publication-title: Nucleic Acids.
  doi: 10.1016/j.omtn.2018.12.003
– ident: B106
– volume: 84
  start-page: 104384
  year: 2020
  ident: B113
  article-title: SARS-CoV-2 and COVID-19: a genetic, epidemiological, and evolutionary perspective
  publication-title: Infect Genet Evolut.
  doi: 10.1016/j.meegid.2020.104384
– volume: 270
  start-page: 475
  year: 1995
  ident: B5
  article-title: T lymphocyte-directed gene therapy for ADASCID: Initial trial results after 4 years
  publication-title: Science
  doi: 10.1126/science.270.5235.475
– volume: 24
  start-page: 1012
  year: 2014
  ident: B95
  article-title: Highly efficient RNA-guided genome editing in human cells via delivery of purified Cas9 ribonucleoproteins
  publication-title: Genome Res.
  doi: 10.1101/gr.171322.113
– volume: 135
  start-page: 189
  year: 2016
  ident: B100
  article-title: Tissue-specific gene targeting using CRISPR/Cas9
  publication-title: Methods Cell Biol.
  doi: 10.1016/bs.mcb.2016.03.004
– volume: 323
  start-page: 570
  year: 1990
  ident: B4
  article-title: Gene transfer into humans–immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction
  publication-title: N Engl J Med.
  doi: 10.1056/NEJM199008303230904
– volume: 4
  start-page: 726
  year: 2019
  ident: B102
  article-title: Engineered materials for in vivo delivery of genome-editing machinery
  publication-title: Nat Rev Mater.
  doi: 10.1038/s41578-019-0145-9
– volume: 25
  start-page: 229
  year: 2019
  ident: B107
  article-title: Development of a gene-editing approach to restore vision loss in Leber congenital amaurosis type 10
  publication-title: Nat Med.
  doi: 10.1038/s41591-018-0327-9
– volume: 576
  start-page: 149
  year: 2019
  ident: B91
  article-title: Search-and-replace genome editing without double-strand breaks or donor DNA
  publication-title: Nature
  doi: 10.1038/s41586-019-1711-4
– volume: 72
  start-page: 463
  year: 2010
  ident: B101
  article-title: Regulation of endothelial permeability via paracellular and transcellular transport pathways
  publication-title: Annu Rev Physiol.
  doi: 10.1146/annurev-physiol-021909-135833
– ident: B115
– volume: 471
  start-page: 602
  year: 2011
  ident: B27
  article-title: CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III
  publication-title: Nature
  doi: 10.1038/nature09886
– volume: 25
  start-page: 249
  year: 2019
  ident: B75
  article-title: Identification of preexisting adaptive immunity to Cas9 proteins in humans
  publication-title: Nat Med.
  doi: 10.1038/s41591-018-0326-x
– volume: 4
  start-page: 96
  year: 2009
  ident: B111
  article-title: The biology of CCR5 and CXCR4
  publication-title: Curr Opin HIV AIDS.
  doi: 10.1097/COH.0b013e328324bbec
– volume: 548
  start-page: 413
  year: 2014
  ident: B112
  article-title: Correction of a pathogenic gene mutation in human embryos
  publication-title: Nature
  doi: 10.1038/nature23305
– volume: 16
  start-page: 587
  year: 2020
  ident: B49
  article-title: Bridge helix arginines play a critical role in Cas9 sensitivity to mismatches
  publication-title: Nat Chem Biol.
  doi: 10.1038/s41589-020-0490-4
– volume: 6
  start-page: eaay6812
  year: 2020
  ident: B98
  article-title: Enhanced CRISPR-Cas9 correction of Duchenne muscular dystrophy in mice by a self-complementary AAV delivery system
  publication-title: Sci Adv.
  doi: 10.1126/sciadv.aay6812
– volume: 17
  start-page: 309
  year: 2017
  ident: B97
  article-title: First-in-human phase 1 CRISPR gene editing cancer trials: are we ready?
  publication-title: Curr Gene Ther.
  doi: 10.2174/1566523217666171121165935
– volume: 18
  start-page: 1891
  year: 2010
  ident: B11
  article-title: Gene therapy for SCID-X1: round 2
  publication-title: Mol Ther.
  doi: 10.1038/mt.2010.228
– volume: 80
  start-page: 148
  year: 2003
  ident: B8
  article-title: Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer
  publication-title: Mol Genet Metab.
  doi: 10.1016/j.ymgme.2003.08.016
– year: 2019
  ident: B109
  article-title: Did CRISPR help—or harm—the first-ever gene-edited babies?
  publication-title: Science
  doi: 10.1126/science.aay9569
– volume: 19
  start-page: 770
  year: 2018
  ident: B90
  article-title: Base editing: precision chemistry on the genome and transcriptome of living cells
  publication-title: Nat Rev Genet.
  doi: 10.1038/s41576-018-0059-1
– volume: 9
  start-page: 297
  year: 2019
  ident: B16
  article-title: Gene therapy leaves a vicious cycle
  publication-title: Front Oncol.
  doi: 10.3389/fonc.2019.00297
– volume: 4
  start-page: e264
  year: 2015
  ident: B31
  article-title: Off-target effects in CRISPR/Cas9-mediated genome engineering
  publication-title: Mol Ther Nucleic Acids.
  doi: 10.1038/mtna.2015.37
– volume: 108
  start-page: 10098
  year: 2011
  ident: B53
  article-title: Interference by clustered regularly interspaced short palindromic repeat (CRISPR) RNA is governed by a seed sequence
  publication-title: Proc Natl Acad Sci USA
  doi: 10.1073/pnas.1104144108
– volume: 118
  start-page: 19
  year: 2011
  ident: B103
  article-title: Fetal hemoglobin in sickle cell anemia
  publication-title: Blood.
  doi: 10.1182/blood-2011-03-325258
– volume: 1368
  start-page: 25
  year: 2016
  ident: B104
  article-title: Regulation of the fetal hemoglobin silencing factor BCL11A
  publication-title: Ann NY Acad Sci
  doi: 10.1111/nyas.13024
– volume: 44
  start-page: 113
  year: 2010
  ident: B81
  article-title: Regulation of homologous recombination in eukaryotes
  publication-title: Annu Rev Genet.
  doi: 10.1146/annurev-genet-051710-150955
– volume: 47
  start-page: 264
  year: 2012
  ident: B1
  article-title: Targeted gene therapies: tools, applications, optimization
  publication-title: Crit Rev Biochem Mol Biol.
  doi: 10.3109/10409238.2012.658112
– volume: 11
  start-page: 399
  year: 2014
  ident: B41
  article-title: Efficient genome modification by CRISPR-Cas9 nickase with minimal off-target effects
  publication-title: Nat Methods.
  doi: 10.1038/nmeth.2857
– volume: 10
  start-page: 455
  year: 2018
  ident: B59
  article-title: Review of CRISPR/Cas9 sgRNA design tools
  publication-title: Interdiscipl Sci Comput Life Sci.
  doi: 10.1007/s12539-018-0298-z
– volume: 14
  start-page: 1555
  year: 2016
  ident: B84
  article-title: Post-translational regulation of Cas9 during G1 enhances homology-directed repair
  publication-title: Cell Rep
  doi: 10.1016/j.celrep.2016.01.019
– volume: 368
  start-page: 290
  year: 2020
  ident: B47
  article-title: Unconstrained genome targeting with near-PAMless engineered CRISPR-Cas9 variants
  publication-title: Science.
  doi: 10.1126/science.aba8853
– volume: 181
  start-page: 865
  year: 2020
  ident: B119
  article-title: Development of CRISPR as an antiviral strategy to combat SARS-CoV-2 and influenza
  publication-title: Cell.
  doi: 10.1016/j.cell.2020.04.020
– volume: 2014
  start-page: 612823
  year: 2014
  ident: B68
  article-title: Disruption of HPV16-E7 by CRISPR/Cas system induces apoptosis and growth inhibition in HPV16 positive human cervical cancer cells
  publication-title: BioMed Res Int.
  doi: 10.1155/2014/612823
– volume: 164
  start-page: 1612
  year: 2001
  ident: B7
  article-title: Death but one unintended consequence of gene-therapy trial
  publication-title: CMAJ.
– volume: 36
  start-page: 765
  year: 2018
  ident: B71
  article-title: Repair of double-strand breaks induced by CRISPR–Cas9 leads to large deletions and complex rearrangements
  publication-title: Nat Biotechnol
  doi: 10.1038/nbt.4192
– volume: 9
  start-page: 613
  year: 1993
  ident: B23
  article-title: Transcription at different salinities of Haloferax mediterranei sequences adjacent to partially modified PstI sites
  publication-title: Mol Microbiol.
  doi: 10.1111/j.1365-2958.1993.tb01721.x
– volume: 556
  start-page: 57
  year: 2018
  ident: B43
  article-title: Evolved Cas9 variants with broad PAM compatibility and high DNA specificity
  publication-title: Nature.
  doi: 10.1038/nature26155
– volume: 38
  start-page: 870
  year: 2020
  ident: B118
  article-title: CRISPR–Cas12-based detection of SARS-CoV-2
  publication-title: Nat Biotechnol.
  doi: 10.1038/s41587-020-0513-4
– volume: 141
  start-page: 6545
  year: 2019
  ident: B51
  article-title: Combined computational–experimental approach to explore the molecular mechanism of SaCas9 with a broadened DNA targeting range
  publication-title: J Am Chem Soc.
  doi: 10.1021/jacs.8b13144
– volume: 516
  start-page: 263
  year: 2014
  ident: B64
  article-title: Programmable RNA recognition and cleavage by CRISPR/Cas9
  publication-title: Nature.
  doi: 10.1038/nature13769
– volume: 475
  start-page: 1955
  year: 2018
  ident: B87
  article-title: CRISPR base editors: genome editing without double-stranded breaks
  publication-title: Biochem J.
  doi: 10.1042/BCJ20170793
– volume: 2
  start-page: 27
  year: 2014
  ident: B2
  article-title: Gene therapy for cancer: present status and future perspective
  publication-title: Mol Cell Ther.
  doi: 10.1186/2052-8426-2-27
– volume: 302
  start-page: 415
  year: 2003
  ident: B12
  article-title: LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1
  publication-title: Science.
  doi: 10.1126/science.1088547
– volume: 15
  start-page: 312
  year: 2018
  ident: B67
  article-title: CRISPR–Cas goes RNA
  publication-title: Nat Methods
  doi: 10.1038/nmeth.4681
– volume: 17
  start-page: 295
  year: 2010
  ident: B18
  article-title: Progress and prospects: immune responses to viral vectors
  publication-title: Gene Ther.
  doi: 10.1038/gt.2009.148
– volume: 25
  start-page: 1234
  year: 2018
  ident: B61
  article-title: Delivering CRISPR: a review of the challenges and approaches
  publication-title: Drug Deliv.
  doi: 10.1080/10717544.2018.1474964
– volume: 7
  start-page: e32724
  year: 2018
  ident: B65
  article-title: RNA-dependent RNA targeting by CRISPR-Cas9
  publication-title: Elife.
  doi: 10.7554/eLife.32724
– volume: 3
  start-page: 677
  year: 2011
  ident: B13
  article-title: Gammaretroviral vectors: biology, technology and application
  publication-title: Viruses.
  doi: 10.3390/v3060677
– volume: 428
  start-page: 963
  year: 2016
  ident: B22
  article-title: Origins of programmable nucleases for genome engineering
  publication-title: J Mol Biol.
  doi: 10.1016/j.jmb.2015.10.014
– volume: 26
  start-page: 425
  year: 2015
  ident: B42
  article-title: Dimeric CRISPR RNA-guided FokI-dCas9 nucleases directed by truncated gRNAs for highly specific genome editing
  publication-title: Hum Gene Ther.
  doi: 10.1089/hum.2015.084
– volume: 20
  start-page: 3623
  year: 2019
  ident: B55
  article-title: Evaluating the efficiency of gRNAs in CRISPR/Cas9 mediated genome editing in poplars
  publication-title: Int J Mol Sci.
  doi: 10.3390/ijms20153623
– volume: 151
  start-page: 2551
  year: 2005
  ident: B25
  article-title: Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin
  publication-title: Microbiology.
  doi: 10.1099/mic.0.28048-0
– volume: 24
  start-page: 927
  year: 2018
  ident: B70
  article-title: CRISPR-Cas9 genome editing induces a p53-mediated DNA damage response
  publication-title: Nat Med.
  doi: 10.1038/s41591-018-0049-z
– volume: 288
  start-page: 669
  year: 2000
  ident: B10
  article-title: Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease
  publication-title: Science.
  doi: 10.1126/science.288.5466.669
– start-page: 200432
  year: 2020
  ident: B116
  article-title: Sensitivity of chest CT for COVID-19: comparison to RT-PCR
  publication-title: Radiology
  doi: 10.1148/radiol.2020200432
– volume: 337
  start-page: 816
  year: 2012
  ident: B28
  article-title: A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity
  publication-title: Science.
  doi: 10.1126/science.1225829
– volume: 300
  start-page: 764
  year: 2003
  ident: B21
  article-title: Enhancing gene targeting with designed zinc finger nucleases
  publication-title: Science.
  doi: 10.1126/science.1079512
– volume: 6
  start-page: 19675
  year: 2016
  ident: B54
  article-title: Sequence features associated with the cleavage efficiency of CRISPR/Cas9 system
  publication-title: Sci Rep.
  doi: 10.1038/srep19675
– volume: 1239
  start-page: 197
  year: 2015
  ident: B30
  article-title: Genome engineering using CRISPR-Cas9 system
  publication-title: Methods Mol Biol.
  doi: 10.1007/978-1-4939-1862-1_10
– volume: 7
  start-page: 12642
  year: 2016
  ident: B99
  article-title: Reprogramming metabolic pathways in vivo with CRISPR/Cas9 genome editing to treat hereditary tyrosinaemia
  publication-title: Nat Commun.
  doi: 10.1038/ncomms12642
– volume: 34
  start-page: 339
  year: 2016
  ident: B80
  article-title: Enhancing homology-directed genome editing by catalytically active and inactive CRISPR-Cas9 using asymmetric donor DNA
  publication-title: Nat Biotechnol
  doi: 10.1038/nbt.3481
– volume: 27
  start-page: 729
  year: 2016
  ident: B96
  article-title: Gene editing of human hematopoietic stem and progenitor cells: promise and potential hurdles
  publication-title: Human Gene Ther.
  doi: 10.1089/hum.2016.107
– start-page: 91
  volume-title: Electroporation Protocols Methods in Molecular Biology.
  year: 2008
  ident: B94
  article-title: Overview of drug delivery and alternative methods to electroporation bt - electroporation protocols: preclinical and clinical gene medicine
  doi: 10.1007/978-1-59745-194-9_6
– volume: 173
  start-page: 665
  year: 2018
  ident: B66
  article-title: Transcriptome engineering with RNA-targeting type VI-D CRISPR effectors
  publication-title: Cell.
  doi: 10.1016/j.cell.2018.02.033
– volume: 32
  start-page: 279
  year: 2014
  ident: B56
  article-title: Improving CRISPR-Cas nuclease specificity using truncated guide RNAs
  publication-title: Nat Biotechnol.
  doi: 10.1038/nbt.2808
– volume: 99
  start-page: 154
  year: 2018
  ident: B77
  article-title: Suppressing Ku70/Ku80 expression elevates homology-directed repair efficiency in primary fibroblasts
  publication-title: Int J Biochem Cell Biol.
  doi: 10.1016/j.biocel.2018.04.011
– volume: 4
  start-page: 111
  year: 2020
  ident: B63
  article-title: High-throughput analysis of the activities of xCas9, SpCas9-NG and SpCas9 at matched and mismatched target sequences in human cells
  publication-title: Nat Biomed Eng.
  doi: 10.1038/s41551-019-0505-1
– volume: 9
  start-page: 3048
  year: 2018
  ident: B46
  article-title: Directed evolution of CRISPR-Cas9 to increase its specificity
  publication-title: Nat Commun.
  doi: 10.1038/s41467-018-05477-x
– volume: 431
  start-page: 34
  year: 2019
  ident: B74
  article-title: A CRISPR-dCas toolbox for genetic engineering and synthetic biology
  publication-title: J Mol Biol.
  doi: 10.1016/j.jmb.2018.06.037
– volume: 116
  start-page: 20969
  year: 2019
  ident: B50
  article-title: Rationally engineered Staphylococcus aureus Cas9 nucleases with high genome-wide specificity
  publication-title: Proc Natl Acad Sci USA.
  doi: 10.1073/pnas.1906843116
– volume: 10
  start-page: 1136
  year: 2019
  ident: B72
  article-title: CRISPR-Cas9 genome editing induces megabase-scale chromosomal truncations
  publication-title: Nat Commun.
  doi: 10.1038/s41467-019-09006-2
– volume: 11
  start-page: 569
  year: 2004
  ident: B17
  article-title: Insertional oncogenesis in gene therapy: how much of a risk?
  publication-title: Gene Ther.
  doi: 10.1038/sj.gt.3302243
– volume: 3
  start-page: e04766
  year: 2014
  ident: B82
  article-title: Enhanced homology-directed human genome engineering by controlled timing of CRISPR/Cas9 delivery
  publication-title: eLife.
  doi: 10.7554/eLife.04766.010
– volume: 321
  start-page: 960
  year: 2008
  ident: B26
  article-title: Small CRISPR RNAs guide antiviral defense in prokaryotes
  publication-title: Science.
  doi: 10.1126/science.1159689
– volume: 33
  start-page: 538
  year: 2015
  ident: B78
  article-title: Increasing the efficiency of precise genome editing with CRISPR-Cas9 by inhibition of nonhomologous end joining
  publication-title: Nat Biotechnol.
  doi: 10.1038/nbt.3190
– volume: 4
  start-page: 9
  year: 2019
  ident: B88
  article-title: Off-targeting of base editors: BE3 but not ABE induces substantial off-target single nucleotide variants
  publication-title: Sig Transduct Target Ther.
  doi: 10.1038/s41392-019-0044-y
– volume: 24
  start-page: 465
  year: 2016
  ident: B3
  article-title: Current progress in therapeutic gene editing for monogenic diseases
  publication-title: Mol Ther.
  doi: 10.1038/mt.2016.5
– volume: 6
  start-page: 2153
  year: 2017
  ident: B62
  article-title: In vivo genome editing in animals using AAV-CRISPR system: applications to translational research of human disease
  publication-title: F1000Res.
  doi: 10.12688/f1000research.11243.1
– volume: 55
  start-page: 105955
  year: 2020
  ident: B114
  article-title: The epidemiology, diagnosis and treatment of COVID-19
  publication-title: Int J Antimicrobial Agents.
  doi: 10.1016/j.ijantimicag.2020.105955
– volume: 550
  start-page: 407
  year: 2017
  ident: B45
  article-title: Enhanced proofreading governs CRISPR-Cas9 targeting accuracy
  publication-title: Nature.
  doi: 10.1038/nature24268
– volume: 43
  start-page: 694
  year: 2016
  ident: B14
  article-title: Informed consent: a clinical trials perspective
  publication-title: Oncol Nurs Forum.
  doi: 10.1188/16.ONF.694-696
– volume: 36
  start-page: 244
  year: 2000
  ident: B24
  article-title: Biological significance of a family of regularly spaced repeats in the genomes of archaea, bacteria and mitochondria
  publication-title: Mol Microbiol.
  doi: 10.1046/j.1365-2958.2000.01838.x
– ident: B20
– volume: 21
  start-page: e3107
  year: 2019
  ident: B92
  article-title: Delivery of CRISPR/Cas9 for therapeutic genome editing
  publication-title: J Gene Med.
  doi: 10.1002/jgm.3107
– volume: 11
  start-page: 1223
  year: 2020
  ident: B48
  article-title: Blackjack mutations improve the on-target activities of increased fidelity variants of SpCas9 with 5′G-extended sgRNAs
  publication-title: Nat Commun.
  doi: 10.1038/s41467-020-15021-5
– volume: 125
  start-page: 2363
  year: 2015
  ident: B105
  article-title: BCL11A deletions result in fetal hemoglobin persistence and neurodevelopmental alterations
  publication-title: J Clin Invest.
  doi: 10.1172/JCI81163
– volume: 361
  start-page: 1259
  year: 2018
  ident: B44
  article-title: Engineered CRISPR-Cas9 nuclease with expanded targeting space
  publication-title: Science.
  doi: 10.1126/science.aas9129
– volume: 9
  start-page: Ge01
  year: 2015
  ident: B19
  article-title: Non viral vectors in gene therapy- an overview
  publication-title: J Clin Diagn Res.
  doi: 10.7860/JCDR/2015/10443.5394
– volume: 96
  start-page: 755
  year: 2017
  ident: B83
  article-title: Virus-mediated genome editing via homology-directed repair in mitotic and postmitotic cells in mammalian brain
  publication-title: Neuron.
  doi: 10.1016/j.neuron.2017.10.004
– volume: 351
  start-page: 84
  year: 2016
  ident: B36
  article-title: Rationally engineered Cas9 nucleases with improved specificity
  publication-title: Science.
  doi: 10.1126/science.aad5227
– volume: 111
  start-page: 9591
  year: 2014
  ident: B108
  article-title: Seamless modification of wild-type induced pluripotent stem cells to the natural CCR5Delta32 mutation confers resistance to HIV infection
  publication-title: Proc Natl Acad Sci USA.
  doi: 10.1073/pnas.1407473111
– volume: 4
  start-page: 43
  year: 2017
  ident: B15
  article-title: Adenovirus-mediated gene delivery: potential applications for gene and cell-based therapies in the new era of personalized medicine
  publication-title: Genes Dis.
  doi: 10.1016/j.gendis.2017.04.001
– volume: 24
  start-page: 1216
  year: 2018
  ident: B39
  article-title: A high-fidelity Cas9 mutant delivered as a ribonucleoprotein complex enables efficient gene editing in human hematopoietic stem and progenitor cells
  publication-title: Nat Med.
  doi: 10.1038/s41591-018-0137-0
– volume: 11
  start-page: 122
  year: 2014
  ident: B57
  article-title: E-CRISP: fast CRISPR target site identification
  publication-title: Nat Methods.
  doi: 10.1038/nmeth.2812
– volume: 339
  start-page: 819
  year: 2013
  ident: B29
  article-title: Multiplex genome engineering using CRISPR/Cas systems
  publication-title: Science.
  doi: 10.1126/science.1231143
– volume: 4
  start-page: eaau0766
  year: 2018
  ident: B52
  article-title: Minimal PAM specificity of a highly similar SpCas9 ortholog
  publication-title: Sci Adv.
  doi: 10.1126/sciadv.aau0766
– volume: 18
  start-page: 190
  year: 2017
  ident: B37
  article-title: Crossing enhanced and high fidelity SpCas9 nucleases to optimize specificity and cleavage
  publication-title: Genome Biol.
  doi: 10.1186/s13059-017-1318-8
– volume: 61
  start-page: 895
  year: 2016
  ident: B34
  article-title: Structural plasticity of PAM recognition by engineered variants of the RNA-guided endonuclease Cas9
  publication-title: Mol Cell.
  doi: 10.1016/j.molcel.2016.02.020
– volume: 36
  start-page: 265
  year: 2018
  ident: B38
  article-title: A highly specific SpCas9 variant is identified by in vivo screening in yeast
  publication-title: Nat Biotechnol.
  doi: 10.1038/nbt.4066
– volume: 6
  start-page: eaaz0051
  year: 2020
  ident: B86
  article-title: Improving the efficiency of precise genome editing with site-specific Cas9-oligonucleotide conjugates
  publication-title: Sci Adv.
  doi: 10.1126/sciadv.aaz0051
– volume: 10
  start-page: 2515
  year: 1999
  ident: B9
  article-title: Gene transfer into the liver of nonhuman primates with E1-deleted recombinant adenoviral vectors: safety of readministration
  publication-title: Hum Gene Ther.
  doi: 10.1089/10430349950016852
– volume: 33
  start-page: 1293
  year: 2015
  ident: B33
  article-title: Broadening the targeting range of Staphylococcus aureus CRISPR-Cas9 by modifying PAM recognition
  publication-title: Nat Biotechnol.
  doi: 10.1038/nbt.3404
– volume: 37
  start-page: 284
  year: 2019
  ident: B85
  article-title: Improving gene editing outcomes in human hematopoietic stem and progenitor cells by temporal control of DNA repair
  publication-title: Stem Cells.
  doi: 10.1002/stem.2935
– volume: 270
  start-page: 470
  year: 1995
  ident: B6
  article-title: Gene therapy in peripheral blood lymphocytes and bone marrow for ADA- immunodeficient patients
  publication-title: Science.
  doi: 10.1126/science.270.5235.470
– volume: 52
  start-page: 1555
  year: 2019
  ident: B93
  article-title: Delivery aspects of CRISPR/Cas for in vivo genome editing
  publication-title: Accounts Chem Res.
  doi: 10.1021/acs.accounts.9b00106
– volume: 36
  start-page: 2684
  year: 2020
  ident: B60
  article-title: Generalizable sgRNA design for improved CRISPR/Cas9 editing efficiency
  publication-title: Bioinformatics.
  doi: 10.1093/bioinformatics/btaa041
SSID ssj0000650103
Score 2.6569543
SecondaryResourceType review_article
Snippet A series of recent discoveries harnessing the adaptive immune system of prokaryotes to perform targeted genome editing is having a transformative influence...
SourceID doaj
pubmedcentral
proquest
pubmed
crossref
SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
Enrichment Source
StartPage 1387
SubjectTerms clinical trial
CRISPR/Cas9
ethics
gene therapy
homology-directed repair (HDR)
non-homologous end joining (NHEJ)
Oncology
Title CRISPR Gene Therapy: Applications, Limitations, and Implications for the Future
URI https://www.ncbi.nlm.nih.gov/pubmed/32850447
https://www.proquest.com/docview/2437844029
https://pubmed.ncbi.nlm.nih.gov/PMC7427626
https://doaj.org/article/6de0e2e0a57e411ca89668dfcfefc5eb
Volume 10
WOSCitedRecordID wos000563457500001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
journalDatabaseRights – providerCode: PRVAON
  databaseName: DOAJ Directory of Open Access Journals
  customDbUrl:
  eissn: 2234-943X
  dateEnd: 99991231
  omitProxy: false
  ssIdentifier: ssj0000650103
  issn: 2234-943X
  databaseCode: DOA
  dateStart: 20110101
  isFulltext: true
  titleUrlDefault: https://www.doaj.org/
  providerName: Directory of Open Access Journals
– providerCode: PRVHPJ
  databaseName: ROAD: Directory of Open Access Scholarly Resources
  customDbUrl:
  eissn: 2234-943X
  dateEnd: 99991231
  omitProxy: false
  ssIdentifier: ssj0000650103
  issn: 2234-943X
  databaseCode: M~E
  dateStart: 20110101
  isFulltext: true
  titleUrlDefault: https://road.issn.org
  providerName: ISSN International Centre
link http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Lb9QwEB5BhRAXRHlugcpIHDiQNnb85FaqruihpSpF2pvl-KFWQlnUbnvkt-Nxsqssouqll0hJHGU8M7G_0Uy-AfgoTcOVd7RC7rKKp8ZXuvGpEoalVstIeatLswl1fKxnM3MyavWFNWE9PXCvuF0ZYh1ZrJ1QkVPqnc4AXYfkU0xexBZX34x6RsFUvwYLbGDQc_nkKMzspnmHjIWs3sHcnFrbhgpb__8g5r-VkqOtZ_oMng6Ykez1sm7Cg9g9h8dHQ1b8BXzfPz38cXJKkEKanPU0AV_I3ig1_ZmUH5mWJ64L5HBUSk4yciUZCZJpYRh5CT-nB2f736qhUULlBROLSsnaBOa4r4VoMuRIKcXAeCNVS1OgwYkMAp2JjAXaIMIJGcRppbIXce-ja17BRjfv4hsglDqWdccli5FLLbWp2zYFx1ObTOJqAjtLvVk_yI3NLH7ZHE2goi0q2qKibVH0BD6tHvjdE2jcPvQrGmI1DJmvy4XsD3bwB3uXP0zgw9KMNn8pmP5wXZxfX1mkXtQ8x8tmAq97s65e1TCdJ43TU2sGX5Nl_U53cV7YuBVneUORW_ch_Ft4guooBYbqHWwsLq_je3jkbxYXV5fb8FDN9HZx9Hw8-nPwFwzSBWQ
linkProvider Directory of Open Access Journals
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=CRISPR+Gene+Therapy%3A+Applications%2C+Limitations%2C+and+Implications+for+the+Future&rft.jtitle=Frontiers+in+oncology&rft.au=Uddin%2C+Fathema&rft.au=Rudin%2C+Charles+M&rft.au=Sen%2C+Triparna&rft.date=2020-08-07&rft.issn=2234-943X&rft.eissn=2234-943X&rft.volume=10&rft.spage=1387&rft_id=info:doi/10.3389%2Ffonc.2020.01387&rft_id=info%3Apmid%2F32850447&rft.externalDocID=32850447
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2234-943X&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2234-943X&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2234-943X&client=summon