Therapeutic gene editing: Delivery and regulatory perspectives

Acta Pharmacologica Sinica

Volumn 38, Issue 6, 2017, Pages 738-753

  Shim, Gayong ^a   Kim, Dongyoon ^a   Park, Gyu Thae ^a   Jin, Hyerim ^a   Suh, Soo Kyung ^b   Oh, Yu Kyoung ^a  

^a Seoul National University   (South Korea)

^b National Institute of Food and Drug Safety Evaluation   (South Korea)

Author keywords

CRISPR Cas9; Delivery system; Gene editing; Regulation; Safety; Transcription activator like effector nuclease; Zinc finger nuclease

Indexed keywords

NUCLEASE;

CARCINOGENICITY; DRUG DISTRIBUTION; EX VIVO STUDY; GENE CONTROL; GENE DELIVERY SYSTEM; GENE EDITING; GENE TARGETING; GENOTOXICITY; HUMAN; IMMUNOGENICITY; IN VIVO STUDY; NONHUMAN; PHARMACOKINETICS; QUALITY CONTROL; REVIEW; SAFETY; CLUSTERED REGULARLY INTERSPACED SHORT PALINDROMIC REPEAT; GENE THERAPY; GENE TRANSFER; GENETICS;

CLUSTERED REGULARLY INTERSPACED SHORT PALINDROMIC REPEATS; GENE EDITING; GENE TRANSFER TECHNIQUES; GENETIC THERAPY; HUMANS;

EID: 85020230732     PISSN: 16714083     EISSN: 17457254     Source Type: Journal    
DOI: 10.1038/aps.2017.2     Document Type: Review

References (126)

1. Cox DBT, Platt RJ, Zhang F. Therapeutic genome editing: prospects and challenges. Nat Med 2015; 21: 121-31.
2. Maeder ML, Gersbach CA. Genome-editing technologies for gene and cell therapy. Mol Ther 2016. doi: 10.1038/mt.2016.10.
3. Urnov FD, Rebar EJ, Holmes MC, Zhang HS, Gregory PD. Genome editing with engineered zinc finger nucleases. Nat Rev Genet 2010; 11: 636-46.
4. Joung JK, Sander JD. Talens: A widely applicable technology for targeted genome editing. Nat Rev Mol Cell Biol 2013; 14: 49-55.
5. Sander JD, Joung JK. CRISPR-Cas systems for editing, regulating and targeting genomes. Nat Biotechnol 2014; 32: 347-55.
6. Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F. Genome engineering using the CRISPR-Cas9 system. Nat Protoc 2013; 8: 2281-308.
7. Gori JL, Hsu PD, Maeder ML, Shen S, Welstead GG, Bumcrot D. Delivery and specificity of CRISPR/Cas9 genome editing technologies for human gene therapy. Hum Gene Ther 2015; 26: 443-51.
8. Li L, He ZY, Wei XW, Gao GP, Wei YQ. Challenges in CRISPR/CAS9 delivery: potential roles of nonviral vectors. Hum Gene Ther 2015; 26: 452-62.
9. LaFountaine JS, Fathe K, Smyth HD. Delivery and therapeutic applications of gene editing technologies ZFNs, TALENs, and CRISPR/Cas9. Int J Pharm 2015; 494: 180-94.
10. Firth AL, Menon T, Parker GS, Qualls SJ, Lewis BM, Ke E, et al. Functional gene correction for cystic fibrosis in lung epithelial cells generated from patient iPSCs. Cell Rep 2015; 12: 1385-90.
11. Xu P, Tong Y, Liu XZ, Wang TT, Cheng L, Wang BY, et al. Both TALENs and CRISPR/Cas9 directly target the HBB IVS2-654 (CT) mutation in -thalassemia-derived iPSCs. Sci Rep 2015; 5: 12065.
12. Xu L, Park KH, Zhao L, Xu J, El Refaey M, Gao Y, et al. CRISPR-mediated genome editing restores dystrophin expression and function in MDX mice. Mol Ther 2016; 24: 564-9.
13. Holt N, Wang J, Kim K, Friedman G, Wang X, Taupin V, et al. Zinc finger nuclease-mediated CCR5 knockout hematopoietic stem cell transplantation controls HIV-1 in vivo. Nat Biotechnol 2010; 28: 839-47.
14. Kim BY, Jeong S, Lee SY, Lee SM, Gweon EJ, Ahn H, et al. Concurrent progress of reprogramming and gene correction to overcome therapeutic limitation of mutant ALK2-iPSC. Exp Mol Med 2016; 48: e237.
15. Valletta S, Dolatshad H, Bartenstein M, Yip BH, Bello E, Gordon S, et al. ASXL1 mutation correction by CRISPR/Cas9 restores gene function in leukemia cells and increases survival in mouse xenografts. Oncotarget 2015; 6: 44061.
16. Kishida T, Ejima A, Mazda O. Specific destruction of HIV proviral p17 gene in T lymphoid cells achieved by the genome editing technology. Front Microbiol 2016; 7: 1001.
17. Bakondi B, Lv W, Lu B, Jones MK, Tsai Y, Kim KJ, et al. In vivo CRISPR/Cas9 gene editing corrects retinal dystrophy in the S334TER-3 rat model of autosomal dominant retinitis pigmentosa. Mol Ther 2016; 24: 556-63.
18. Butler JR, Wang ZY, Martens GR, Ladowski JM, Li P, Tector M, et al. Modified glycan models of pig-to-human xenotransplantation do not enhance the human-anti-pig T cell response. Transpl Immunol 2016; 35: 47-51.
19. Osborn MJ, Starker CG, McElroy AN, Webber BR, Riddle MJ, Xia L, et al. TALEN-based gene correction for epidermolysis bullosa. Mol Ther 2013; 21: 1151-9.
20. Merling RK, Sweeney CL, Chu J, Bodansky A, Choi U, Priel DL, et al. An AAVS1-targeted minigene platform for correction of iPSCs from all five types of chronic granulomatous disease. Mol Ther 2015; 23: 147-57.
21. Hoban MD, Cost GJ, Mendel MC, Romero Z, Kaufman ML, Joglekar AV, et al. Correction of the sickle cell disease mutation in human hematopoietic stem/progenitor cells. Blood 2015; 125: 2597-604.
22. Mock U, Machowicz R, Hauber I, Horn S, Abramowski P, Berdien B, et al. mRNA transfection of a novel TAL effector nuclease (TALEN) facilitates efficient knockout of HIV co-receptor CCR5. Nucleic Acids Res 2015; 43: 5560-71.
23. Kim S, Kim D, Cho SW, Kim J, Kim J. Highly efficient RNA-guided genome editing in human cells via delivery of purified Cas9 ribonucleoproteins. Genome Res 2014; 24: 1012-9.
24. Zuris JA, David B, Thompson DB, Yilai Shu Y, John P Guilinger JP, et al. Cationic lipid-mediated delivery of proteins enables efficient protein-based genome editing in vitro and in vivo. Nat Biotech 2015; 33: 73-80.
25. Wang M, Zuris JA, Meng F, Rees H, Sun S, Deng P, et al. Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles. Proc Natl Acad Sci U S A 2016; 113: 2868-73.
26. Ramakrishna S, Kwaku Dad AB, Beloor J, Gopalappa R, Lee SK, Kim H. Gene disruption by cell-penetrating peptide-mediated delivery of Cas9 protein and guide RNA. Genome Res 2014; 24: 1020-7.
27. Liu J, Gaj T, Patterson JT, Sirk SJ, Barbas CF 3rd. Cell-penetrating peptide-mediated delivery of TALEN proteins via bioconjugation for genome engineering. PLoS One 2014; 9: e85755.
28. Gaj T, Guo J, Kato Y, Sirk SJ, Barbas III CF. Targeted gene knockout by direct delivery of zinc-finger nuclease proteins. Nat Methods 2012; 9: 805-7.
29. Murlidharan G, Sakamoto K, Rao L, Corriher T, Wang D, Gao G, et al. CNS-restricted transduction and CRISPR/Cas9-mediated gene deletion with an engineered AAV vector. Mol Ther Nucleic Acids 2016; 5: e338.
30. Abebordbar M, Zhu K, Cheng JK, Chew WL, Widrick JJ, Yan WX, et al. In vivo gene editing in dystrophic mouse muscle and muscle stem cells. Science 2016; 351: 407-11.
31. Yang Y, Wang L, Bell P, McMenamin D, He Z, White J, et al. A dual AAV system enables the Cas9-mediated correction of a metabolic liver disease in newborn mice. Nat Biotechnol 2016; 34: 334-8.
32. Anguela XM, Sharma R, Doyon Y, Miller JC, Li H, Haurigot V, et al. Robust ZFN-mediated genome editing in adult hemophilic mice. Blood 2013; 122: 3283-7.
33. Landau DJ, Brooks ED, Perez-Pinera P, Amarasekara H, Mefferd A, Li S, et al. In vivo zinc finger nuclease-mediated targeted integration of a glucose-6-phosphatase transgene promotes survival in mice with glycogen storage disease type IA. Mol Ther 2016; 24: 697-706.
34. Li C, Guan X, Du T, Jin W, Wu B, Liu Y, et al. Inhibition of HIV-1 infection of primary CD4+ T-cells by gene editing of CCR5 using adenovirus-delivered CRISPR/Cas9. J Gen Virol 2015; 96: 2381-93.
35. Li C, Ding L, Sun CW, Wu LC, Zhou D, Pawlik KM, et al. Novel HDAD/EBV reprogramming vector and highly efficient ad/CRISPR-Cas sickle cell disease gene correction. Sci Rep 2016; 6: 30422.
36. Yuan J, Wang J, Crain K, Fearns C, Kim KA, Hua KL, et al. Zinc-finger nuclease editing of human CXCR4 promotes HIV-1 CD4+ T cell resistance and enrichment. Mol Ther 2012; 20: 849-59.
37. Li L, Krymskaya L, Wang J, Henley J, Rao A, Cao LF, et al. Genomic editing of the HIV-1 coreceptor CCR5 in adult hematopoietic stem and progenitor cells using zinc finger nucleases. Mol Ther 2013; 21: 1259-69.
38. Hou P, Chen S, Wang S, Yu X, Chen Y, Jiang M, et al. Genome editing of CXCR4 by CRISPR/Cas9 confers cells resistant to HIV-1 infection. Sci Rep 2015; 5: 15577.
39. Kaminski R, Chen Y, Fischer T, Tedaldi E, Napoli A, Zhang Y, et al. Elimination of HIV-1 genomes from human T-lymphoid cells by CRISPR/Cas9 gene editing. Sci Rep 2016; 6: 22555.
40. Karimova M, Beschorner N, Dammermann W, Chemnitz J, Indenbirken D, Bockmann JH, et al. CRISPR/Cas9 nickase-mediated disruption of hepatitis B virus open reading frame S and X. Sci Rep 2015; 5: 13734.
41. Roehm PC, Shekarabi M, Wollebo HS, Bellizzi A, He L, Salkind J, et al. Inhibition of HSV-1 replication by gene editing strategy. Sci Rep 2016; 6: 23146.
42. Shin MH, He Y, Marrogi E, Piperdi S, Ren L, Khanna C, et al. A RUNX2-mediated epigenetic regulation of the survival of p53 defective cancer cells. PLoS Genet 2016; 12: e1005884.
43. Dong C, Qu L, Wang H, Wei L, Dong Y, Xiong S. Targeting hepatitis B virus cccDNA by CRISPR/Cas9 nuclease efficiently inhibits viral replication. Antiviral Res 2015; 118: 110-7.
44. Zhu W, Xie K, Xu Y, Wang L, Chen K, Zhang L, et al. CRISPR/Cas9 produces anti-hepatitis B virus effect in hepatoma cells and transgenic mouse. Virus Res 2016; 217: 125-32.
45. Cradick TJ, Keck K, Bradshaw S, Jamieson AC, McCaffrey AP. Zinc-finger nucleases as a novel therapeutic strategy for targeting hepatitis B virus DNAs. Mol Ther 2010; 18: 947-54.
46. Badia R, Riveira-Muñoz E, Clotet B, Esté JA, Ballana E. Gene editing using a zinc-finger nuclease mimicking the CCR532 mutation induces resistance to CCR5-using HIV-1. J Antimicrob Chemother 2014; 69: 1755-9.
47. Liao H, Xiao Y, Hu Y, Xiao Y, Yin Z, Liu L. Suppression of cellular proliferation and invasion by HMGB1 knockdown in bladder urothelial carcinoma cells. Oncol Res 2015; 22: 235-45.
48. Lee CM, Flynn R, Hollywood JA, Scallan MF, Harrison PT. Correction of the F508 mutation in the cystic fibrosis transmembrane conductance regulator gene by zinc-finger nuclease homology-directed repair. Biores Open Access 2012; 1: 99-108.
49. Yao Y, Nashun B, Zhou T, Qin L, Qin L, Zhao S, et al. Generation of CD34+ cells from CCR5-disrupted human embryonic and induced pluripotent stem cells. Hum Gene Ther 2011; 23: 238-42.
50. Hu Z, Ding W, Zhu D, Yu L, Jiang X, Wang X, et al. TALEN-mediated targeting of HPV oncogenes ameliorates HPV-related cervical malignancy. J Clin Invest 2015; 125: 425-36.
51. Ding W, Hu Z, Zhu D, Jiang X, Yu L, Wang X, et al. Zinc finger nucleases targeting the human papillomavirus E7 oncogene induce E7 disruption and a transformed phenotype in HPV16/18-positive cervical cancer cells. Clin Cancer Res 2014; 20: 6495-503.
52. Sun N, Liang J, Abil Z, Zhao H. Optimized TAL effector nucleases (TALENs) for use in treatment of sickle cell disease. Mol Biosyst 2012; 8: 1255-63.
53. Guideline on human cell-based medicinal products. European Medicines Agency 2008.
54. Note for guidance on the quality, preclinical and clinical aspects of gene transfer medicinal products. European Medicines Agency 2001.
55. Supplemental guidance on testing for replication competent retrovirus in retroviral vector based gene therapy products and during follow-up of patients in clinical trials using retroviral vectors. US. Food and Drug Administration 2006.
56. Content and review of chemistry, manufacturing, and control (CMC) information for human gene therapy investigational new drug applications (INDs). US. Food and Drug Administration 2008.
57. Guideline on the non-clinical studies before first clinical use of gene therapy medicinal products. European Medicines Agency 2008.
58. Guideline on non-clinical testing for inadvertent germline transmission of gene transfer vectors. European Medicines Agency 2006.
59. Preclinical assessment of investigational cellular and gene therapy products. US. Food and Drug Administration 2013.
60. Guideline on quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells. European Medicines Agency 2012.
61. Potency tests for cellular and gene therapy products. US. Food and Drug Administration 2011.
62. Gaj T, Gersbach CA, Barbas CF. ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol 2013; 31: 397-405.
63. Kim Y, Kweon J, Kim A, Chon JK, Yoo JY, Kim HJ, et al. A library of TAL effector nucleases spanning the human genome. Nat Biotechnol 2013; 31: 251-8.
64. Makarova KS, Haft DH, Barrangou R, Brouns SJ, Charpentier E, Horvath P, et al. Evolution and classification of the CRISPR-Cas systems. Nat Rev Microbiol 2011; 9: 467-77.
65. Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, et al. Multiplex genome engineering using CRISPR/Cas systems. Science 2013; 339: 819-23.
66. Sung LY, Chen CL, Lin SY, Li KC, Yeh CL, Chen GY, et al. Efficient gene delivery into cell lines and stem cells using baculovirus. Nat Protoc 2014; 9: 1882-99.
67. Choi J, Dang Y, Abraham S, Ma H, Zhang J, Guo H, et al. Lentivirus pre-packed with Cas9 protein for safer gene editing. Gene Ther 2016; 23: 627-33.
68. Bellec J, Bacchetta M, Losa D, Anegon I, Chanson M, Huy Nguyen T. CFTR inactivation by lentiviral vector-mediated rna interference and CRISPR-Cas9 genome editing in human airway epithelial cells. Curr Gene Ther 2015; 15: 447-59.
69. Benabdallah BF, Duval A, Rousseau J, Chapdelaine P, Holmes MC, Haddad E, et al. Targeted gene addition of microdystrophin in mice skeletal muscle via human myoblast transplantation. Mol Ther Nucleic Acids 2013; 2: e68.
70. Araki M, Ishii T. Providing appropriate risk information on genome editing for patients. Trends Biotechnol 2016; 34: 86-90.
71. Yin H, Kanasty RL, Eltoukhy AA, Vegas AJ, Dorkin JR, Anderson DG. Non-viral vectors for gene-based therapy. Nat Rev Genet 2014; 15: 541-55.
72. Yin C, Zhang T, Li F, Yang F, Putatunda R, Young WB, et al. Functional screening of guide RNAs targeting the regulatory and structural HIV-1 viral genome for a cure of AIDS. AIDS 2016; 30: 1163-74.
73. Maggio I, Stefanucci L, Janssen JM, Liu J, Chen X, Mouly V, et al. Selection-free gene repair after adenoviral vector transduction of designer nucleases: Rescue of dystrophin synthesis in DMD muscle cell populations. Nucleic Acids Res 2016; 44: 1449-70.
74. Li M, Zhao H, Ananiev GE, Musser MT, Ness KH, Maglaque DL, et al. Establishment of reporter lines for detecting fragile X mental retardation (FMR1) gene reactivation in human neural cells. Stem Cells 2016. doi: 10.1002/stem.2463.
75. Su S, Hu B, Shao J, Shen B, Du J, Du Y, et al. CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients. Sci Rep 2016; 6: 20070.
76. Wu B, Jiang WG, Zhou D, Cui YX. Knockdown of EPHA1 by CRISPR/Cas9 promotes adhesion and motility of HRT18 colorectal carcinoma cells. Anticancer Res 2016; 36: 1211-9.
77. Young CS, Hicks MR, Ermolova NV, Nakano H, Jan M, Younesi S, et al. A single CRISPR-Cas9 deletion strategy that targets the majority of DMD patients restores dystrophin function in hiPSC-derived muscle cells. Cell Stem Cell 2016; 18: 533-40.
78. Sebastiano V, Maeder ML, Angstman JF, Haddad B, Khayter C, Yeo DT, et al. In situ genetic correction of the sickle cell anemia mutation in human induced pluripotent stem cells using engineered zinc finger nucleases. Stem Cells 2011; 29: 1717-26.
79. Manotham K, Chattong S, Setpakdee A. Generation of CCR5-defective CD34 cells from ZFN-driven stop codon-integrated mesenchymal stem cell clones. J Biomed Sci 2015; 22: 1.
80. Ma N, Liao B, Zhang H, Wang L, Shan Y, Xue Y, et al. Transcription activator-like effector nuclease (TALEN)-mediated gene correction in integration-free -thalassemia induced pluripotent stem cells. J Biol Chem 2013; 288: 34671-9.
81. Nyquist MD, Li Y, Hwang TH, Manlove LS, Vessella RL, Silverstein KA, et al. TALEN-engineered AR gene rearrangements reveal endocrine uncoupling of androgen receptor in prostate cancer. Proc Natl Acad Sci U S A 2013; 110: 17492-7.
82. Park C-Y, Kim J, Kweon J, Son JS, Lee JS, Yoo J-E, et al. Targeted inversion and reversion of the blood coagulation factor 8 gene in human iPS cells using TALENs. Proc Natl Acad Sci U S A 2014; 111: 9253-8.
83. Garate Z, Quintana-Bustamante O, Crane AM, Olivier E, Poirot L, Galetto R, et al. Generation of a high number of healthy erythroid cells from gene-edited pyruvate kinase deficiency patient-specific induced pluripotent stem cells. Stem Cell Rep 2015; 5: 1053-66.
84. Ousterout DG, Kabadi AM, Thakore PI, Perez-Pinera P, Brown MT, Majoros WH, et al. Correction of dystrophin expression in cells from duchenne muscular dystrophy patients through genomic excision of exon 51 by zinc finger nucleases. Mol Ther 2015; 23: 523-32.
85. Niu X, He W, Song B, Ou Z, Fan D, Chen Y, et al. Combining single-strand oligodeoxynucleotides and CRISPR/Cas9 to correct gene mutations in beta-thalassemia-induced pluripotent stem cells. J Biol Chem 2016. doi: 10.1074/jbc.M116.719237.
86. Dreyer A-K, Hoffmann D, Lachmann N, Ackermann M, Steinemann D, Timm B, et al. TALEN-mediated functional correction of X-linked chronic granulomatous disease in patient-derived induced pluripotent stem cells. Biomaterials 2015; 69: 191-200.
87. Mianné J, Chessum L, Kumar S, Aguilar C, Codner G, Hutchison M, et al. Correction of the auditory phenotype in C57BL/6N mice via CRISPR/Cas9-mediated homology directed repair. Genome Med 2016; 8: 16.
88. Cottle RN, Lee CM, Archer D, Bao G. Controlled delivery of -globin-targeting TALENs and CRISPR/Cas9 into mammalian cells for genome editing using microinjection. Sci Rep 2015; 5: 16031.
89. Park CY, Kim DH, Son JS, Sung JJ, Lee J, Bae S, et al. Functional correction of large factor viii gene chromosomal inversions in hemophilia a patient-derived iPSCs using CRISPR-Cas9. Cell Stem Cell 2015; 17: 213-20.
90. Hu Z, Yu L, Zhu D, Ding W, Wang X, Zhang C, et al. Disruption of HPV16-E7 by CRISPR/Cas system induces apoptosis and growth inhibition in HPV16 positive human cervical cancer cells. BioMed Res Int 2014; 2014: 612823.
91. Osborn MJ, Gabriel R, Webber BR, DeFeo AP, McElroy AN, Jarjour J, et al. Fanconi anemia gene editing by the CRISPR/Cas9 system. Hum Gene Ther 2014; 26: 114-26.
92. Fadel HJ, Morrison JH, Saenz DT, Fuchs JR, Kvaratskhelia M, Ekker SC, et al. TALEN knockout of the psip1 gene in human cells: Analyses of HIV-1 replication and allosteric integrase inhibitor mechanism. J Virol 2014; 88: 9704-17.
93. Hoban MD, Lumaquin D, Kuo CY, Romero Z, Long J, Ho M, et al. CRISPR/Cas9-mediated correction of the sickle mutation in human cd34+ cells. Mol Ther 2016; 24: 1561-9.
94. Yin H, Song CQ, Dorkin JR, Zhu LJ, Li Y, Wu Q, et al. Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo. Nat Biotechnol 2016; 34: 328-33.
95. Tebas P, Stein D, Tang WW, Frank I, Wang SQ, Lee G, et al. Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N Engl J Med 2014; 370: 901-10.
96. Kohn DB, Porteus MH, Scharenberg AM. Ethical and regulatory aspects of genome editing. Blood 2016; 127: 2553-60.
97. Guidelines on the quality, safety, and efficacy of biotherapeutic products prepared by recombinant DNA technology. World Health Organization 2013.
98. Maggio I, Gonçalves MA. Genome editing at the crossroads of delivery, specificity, and fidelity. Trends Biotechnol 2015; 33: 280-91.
99. Nelson CE, Gersbach CA. Engineering delivery vehicles for genome editing. Annu Rev Chem Biomol Eng 2016; 7: 637-62.
100. Gori, JL, Hsu PD, Maeder ML, Shen S, Welstead GG, Bumcrot D. Delivery and specificity of CRISPR/Cas9 genome editing technologies for human gene therapy. Hum Gene Ther 2015; 26: 443-51.
101. Zhang XH, Tee LY, Wang XG, Huang QS, Yang SH. Off-target effects in CRISPR/Cas9-mediated genome engineering. Mol Ther Nucleic Acids 2015; 4: e264.
102. Cho SW, Kim S, Kim Y, Kweon J, Kim HS, Bae SB, et al. Analysis of off-target effects of CRISPR/Cas-derived RNA-guided endonucleases and nickases. Genome Res 2014; 24: 132-41.
103. Tsai, SQ, Zheng Z, Nguyen NT, Liebers M, Topkar VV, Thapar V, et al. GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases. Nat Biotechnol 2015; 33: 187-97.
104. Kim, D, Bae S, Park J, Kim E, Kim S, Yu HR, et al. Digenome-seq: genome-wide profiling of CRISPR-Cas9 off-target effects in human cells. Nat Methods 2015; 12: 237-43.
105. Shen B, Zhang W, Zhang J, Zhou J, Wang J, Chen L, et al. Efficient genome modification by CRISPR-Cas9 nickase with minimal off-target effects. Nat Methods 2014; 11: 399-402.
106. Liang P, Xu Y, Zhang X, Ding C, Huang R, Zhang Z, et al. CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein Cell 2015; 6: 363-72.
107. Wang D, Mou H, Li S, Li Y, Hough S, Tran K, et al. Adenovirus-mediated somatic genome editing of Pten by CRISPR/Cas9 in mouse liver in spite of Cas9-specific immune responses. Hum Gene Ther 2015; 26: 432-42.
108. Zaiss AK, Muruve DA. Immune responses to adeno-associated virus vectors. Curr Gene Ther 2005; 5: 323-31.
109. Dai WJ, Zhu LY, Yan ZY, Xu Y, Wang QL, Lu XJ. CRISPR-Cas9 for in vivo gene therapy: promise and hurdles. Mol Ther Nucleic Acid 2016; 5: 349.
110. Mingozzi F, High KA. Immune responses to AAV in clinical trials. Curr Gene Ther 2011; 11: 321-30.
111. Hareendran S, Balakrishnan B, Sen D, Kumar S, Srivastava A, Jayandharan GR. Adeno-associated virus (AAV) vectors in gene therapy: immune challenges and strategies to circumvent them. Rev Med Virol 2013; 23: 399-413.
112. Mingozzi F, High KA. Immune responses to AAV vectors: overcoming barriers to successful gene therapy. Blood 2013; 122: 23-36.
113. Norelli M, Casucci M, Bonini C, Bondanza A. Clinical pharmacology of CAR-T cells: linking cellular pharmacodynamics to pharmacokinetics and antitumor effects. Biochim Biophys Acta 2016; 1865: 90-100.
114. Li HL, Li S, Shao JY, Lin XB, Cao Y, Jiang WQ, et al. Pharmacokinetic and pharmacodynamic study of intratumoral injection of an adenovirus encoding endostatin in patients with advanced tumors. Gene Ther 2008; 15: 247-56.
115. Green NK, Seymour LW. Adenoviral vectors: systemic delivery and tumor targeting. Cancer Gene Ther 2002; 9: 1036-42.
116. Guideline on the clinical investigation of the pharmacokinetics of therapeutic proteins. European Medicines Agency 2007.
117. Nishikawa M, Takakura Y, Hashida M. Pharmacokinetic considerations regarding non-viral cancer gene therapy. Cancer Sci 2008; 99: 856-62.
118. Hacein-Bey-Abina S, Garrigue A, Wang GP, Soulier J, Lim A, Morillon E, et al. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J Clin Invest 2008; 118: 3132-42.
119. Lee AS, Tang C, Rao MS, Weissman IL, Wu JC. Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies. Nat Med 2013; 19: 998-1004.
120. Kohn DB, Porteus MH, Scharenberg AM. Ethical and regulatory aspects of genome editing. Blood 2016; 127: 2553-60.
121. Chira S, Jackson CS, Oprea I, Ozturk F, Pepper MS, Diaconu I, et al. Progresses towards safe and efficient gene therapy vectors. Oncotarget 2015; 6: 30675.
122. Araki M, Ishii T. International regulatory landscape and integration of corrective genome editing into in vitro fertilization. Reprod Biol Endocrinol 2014; 12: 1.
123. Xue HY, Zhang X, Wang Y, Xiaojie L, Dai WJ, Xu Y. In vivo gene therapy potentials of CRISPR-Cas9. Gene Ther 2016; 23: 557-9.
124. Guidance for human somatic cell therapy and gene therapy. U.S. Food and Drug Administration 1998.
125. Maeder ML, Gersbach CA. Genome-editing technologies for gene and cell therapy. Mol Ther 2016; 24: 430-46.
126. Gene therapy product quality aspects in the production of vectors and genetically modified somatic cells. European Medicines Agency 1995.