RESEARCH PROGRESS OF IN VIVO NUCLEIC ACID DELIVERY WITH POLY (ETHYLENIMINE)_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

FENGGanjun , LIULimin , GONGQuan , LITao , LIUHao ,  SONGYueming

Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P. R. China;

Corresponding author：

SONGYueming, Email: sym_cd@aliyun.com

Keywords：

Poly(ethylenimine); Non-viral vector; Nucleic acid del ivery

DOI：

10.7507/1002-1892.20140334

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To review the current status and advances of in vivo nucleic acid del ivery mediated by poly(ethylenimine) (PEI). Methods The related home and abroad literature about nucleic acid del ivery with applications in cancer treatments and tissue engineering was extensively reviewed and analyzed. Results A variety of in vivo study on the potential of PEI-mediated nucleic acid del ivery has been carried out and made certain effects in the animal model, ranging from cancer treatments to rectification of physiological defects (eg. cranial defect and corneal epithelium defect). Tail vein injection is the most commonly adopted route of administration in vivo, followed by pulmonary administration and intralesional injection. However, transfection and expression in vivo have some shortcomings, such as low transfection efficiency and short expression time, so there are some limitation in the cl inical application. Conclusion PEI mediated nucleic acid del ivery provides a good method for cancer treatments and rectification of physiological defects. For future research, not only should more in vivo animal testing be done, but the procedures of experimentation also need to be standardized.

Citation： FENGGanjun, LIULimin, GONGQuan, LITao, LIUHao, SONGYueming. RESEARCH PROGRESS OF IN VIVO NUCLEIC ACID DELIVERY WITH POLY (ETHYLENIMINE). Chinese Journal of Reparative and Reconstructive Surgery, 2014, 28(12): 1544-1550. doi: 10.7507/1002-1892.20140334 Copy

1.	Bank A, Dorazio R, Leboulch P. A phase I/Ⅱ cl inical trial of beta-globin gene therapy for beta-thalassemia. Ann N Y Acad Sci, 2005, 1054: 308-316.
2.	Pearson S, Jia H, Kandachi K. China approves first gene therapy. Nat Biotechnol, 2004, 22(1):3-4.
3.	Kopatz I, Remy JS, Behr JP. A model for non-viral gene del ivery: through syndecan adhesion molecules and powered by actin. J Gene Med, 2004, 6(7):769-776.
4.	Boussif O, Lezoualćh F, Zanta MA, et al. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo:polyethylenimine. Proc Natl Acad Sci U S A, 1995, 92(16):7297-7301.
5.	Kunath K, von Harpe A, Fischer D, et al. Low-molecular-weight polyethylenimine as a non-viral vector for DNA del ivery:comparison of physicochemical properties, transfection efficiency and in vivo distribution with high-molecular-weight polyethylenimine. J Control Release, 2003, 89(1):113-125.
6.	von Harpe A, Petersen H, Li Y, et al. Characterization of commercially available and synthesized polyethylenimines for gene delivery. J Control Release, 2000, 69(2):309-322.
7.	Fischer D, Bieber T, Li Y, et al. A novel non-viral vector for DNA del ivery based on low molecular weight, branched polyethylenimine: effect of molecular weight on transfection efficiency and cytotoxicity. Pharm Res, 1999, 16(8):1273-1279.
8.	Lungwitz U, Breunig M, Blunk T, et al. Polyethylenimine-based nonviral gene delivery systems. Eur J Pharm Biopharm, 2005, 60(2):247-266.
9.	Zou SM, Erbacher P, Remy JS, et al. Systemic linear polyethylenimine (L-PEI)-mediated gene delivery in the mouse. J Gene Med, 2000, 2(2): 128-134.
10.	Brunner S, Sauer T, Carotta S, et al. Cell cycle dependence of gene transfer by l i poplex, polyplex and recombinant adenovirus. Gene Ther, 2000, 7(5):401-407.
11.	Brunner S, Fürtbauer E, Sauer T, et al. Overcoming the nuclear barrier: cell cycle independent nonviral gene transfer with linear polyethylenimine or electroporation. Mol Ther, 2002, 5(1):80-86.
12.	Wightman L, Kircheis R, Rössler V, et al. Different behavior of branched and linear polyethylenimine for gene delivery in vitro and in vivo. J Gene Med, 2001, 3(4):362-372.
13.	Goula D, Remy JS, Erbacher P, et al. Size, diffusibil ity and transfection performance of linear PEI/DNA complexes in the mouse central nervous system. Gene therapy, 1995, (5):712-717.
14.	Rudolph C, Ortiz A, Schillinger U, et al. Methodological optimization of polyethylenimine (PEI)-based gene delivery to the lungs of mice via aerosol application. J Gene Med, 2005, 7(1):59-66.
15.	Min SH, Lee DC, Lim MJ, et al. A composite gene delivery system consisting of polyethylenimine and an amphipathic peptide KALA. J Gene Med, 2006, 8(12):1425-1434.
16.	Jeudy G, Salvadori F, Chauffert B, et al. Polyethylenimine-mediated in vivo gene transfer of a transmembrane superantigen fusion construct inhibits B16 murine melanoma growth. Cancer Gene Ther, 2008, 15(11):742-749.
17.	Tada Y, Kitahara T, Yoshioka T, et al. Partial hepatectomy enhances polyethylenimine-mediated plasmid DNA del ivery. Biol Pharm Bull, 2006, 29(8):1712-1716.
18.	Morille M, Passirani C, Vonarbourg A, et al. Progress in developing cationic vectors for non-viral systemic gene therapy against cancer. Biomaterials, 2008, 29(24-25):3477-3496.
19.	Ogris M, Brunner S, Schüller S, et al. PEGylated DNA/transferrin-PEI complexes:reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery. Gene Ther, 1999, 6(4):595-605.
20.	Mishra S, Webster P, Davis ME. PEGylation significantly affects cellular uptake and intracellular trafficking of non-viral gene del ivery particles. Eur J Cell Biol, 2004, 83(3):97-111.
21.	Chen J, Gao X, Hu K, et al. Galactose-poly(ethylene glycol)-polyethylenimine for improved lung gene transfer. Biochem Biophysical Res Commun, 2008, 375(3):378-383.
22.	Kleemann E, Neu M, Jekel N, et al. Nano-carriers for DNA del ivery to the lung based upon a TAT-derived peptide covalently coupled to PEG-PEI. J Control Release, 2005, 109(1-3):299-316.
23.	Bivas-Benita M, Lin MY, Bal SM, et al. Pulmonary del ivery of DNA encoding Mycobacterium tuberculosis latency antigen Rv1733c associated to PLGA-PEI nanoparticles enhances T cell responses in a DNA prime/protein boost vaccination regimen in mice. Vaccine, 2009, 27(30):4010-4017.
24.	Sasaki H, Yoshida S, Kitahara T, et al. Influence of disease stage on polyethylenimine-mediated plasmid DNA delivery in murine hepatitis. Int J Pharm, 2006, 318(1-2):139-145.
25.	Liu Y, Tao J, Li Y, et al. Targeting hypoxia-inducible factor-1alpha with Tf-PEI-shRNA complex via transferrin receptor-mediated endocytosis inhibits melanoma growth. Mol Ther, 2009, 17(2):269-277.
26.	Di Gioia S, Rejman J, Carrabino S, et al. Role of biophysical parameters on ex vivo and in vivo gene transfer to the airway epithelium by polyethylenimine/albumin complexes. Biomacromolecules, 2008, 9(3): 859-866.
27.	Iwai M, Harada Y, Tanaka S, et al. Polyethylenimine-mediated suicide gene transfer induces a therapeutic effect for hepatocellular carcinoma in vivo by using an Epstein-Barr virus-based plasmid vector. Biochem Biophys Res Commun, 2002, 291(1):48-54.
28.	Grosse S, Thevenot G, Aron Y, et al. In vivo gene delivery in the mouse lung with lactosylated polyethylenimine, questioning the relevance of in vitro experiments. J Control Release, 2008, 132(2):105-112.
29.	Moffatt S, Wiehle S, Cristiano RJ. Tumor-specific gene delivery mediated by a novel peptide-polyethylenimine-DNA polyplex targeting aminopeptidase N/CD13. Hum Gene Ther, 2005, 16(1):57-67.
30.	Huang YC, Riddle K, Rice KG, et al. Long-term in vivo gene expression via delivery of PEI-DNA condensates from porous polymer scaffolds. Hum Gene Ther, 2005, 16(5):609-617.
31.	Kawazu T, Kanzaki H, Uno A, et al. HVJ-E/importin-β hybrid vector for overcoming cytoplasmic and nuclear membranes as double barrier for non-viral gene del ivery. Biomed Pharmacother, 2012, 66(7):519-524.
32.	Liu Y, Steele T, Kissel T. Degradation of Hyper-Branched Poly(ethylenimine)-graft-poly(caprolactone)-block-monomethoxylpoly( ethylene glycol) as a Potential Gene Del ivery Vector. Macromol Rapid Commun, 2010, 31(17):1509-1515.
33.	d'Ayala GG, Calarco A, Malinconico M, et al. Cationic copolymers nanoparticles for nonviral gene vectors:synthesis, characterization, and application in gene delivery. J Biomed Mater Res A, 2010, 94(2): 619-630.
34.	Orsi S, De Capua A, Guarnieri D, et al. Cell recruitment and transfection in gene activated collagen matrix. Biomaterials, 2010, 31(3):570-576.
35.	Mountziaris PM, Tzouanas SN, Sing DC, et al. Intra-articular controlled release of anti-inflammatory siRNA with biodegradable polymer microparticles ameliorates temporomandibular joint inflammation. Acta Biomater, 2012, 8(10):3552-3560.
36.	Pi Y, Zhang X, Shi J, et al. Targeted delivery of non-viral vectors to cartilage in vivo using a chondrocyte-homing peptide identified by phage display. Biomaterials, 2011, 32(26):6324-6332.
37.	Kuo CN, Yang LC, Wu PC, et al. Dehydrated form of plasmid expressing basic fibroblast growth factor-polyethylenimine complex is a novel and accurate method for gene transfer to the cornea. Curr Eye Res, 2005, 30(11):1015-1024.
38.	Yuan J, Liu Y, Weilan H, et al. An experimental study on in situ transfection of the interleukin-1 receptor antagonist (IL-1ra) gene into the rat cornea. Curr Eye Res, 2012, 37(11):997-1004.
39.	Zhou X, Liu B, Yu X, et al. Controlled release of PEI/DNA complexes from PLGA microspheres as a potent del ivery system to enhance immune response to HIV vaccine DNA prime/MVA boost regime. Eur J Pharm Biopharm, 2008, 68(3):589-595.
40.	Zhou X, Liu B, Yu X, et al. Controlled release of PEI/DNA complexes from mannose-bearing chitosan microspheres as a potent del ivery system to enhance immune response to HBV DNA vaccine. J Control Release, 2007, 121(3):200-207.
41.	Thomas M, Lu JJ, Ge Q, et al. Full deacylation of polyethylenimine dramatically boosts its gene delivery efficiency and specificity to mouse lung. Proc Natl Acad Sci U S A, 2005, 102(16):5679-5684.
42.	Jiang G, Park K, Kim J, et al. Target specific intracellular del ivery of siRNA/PEI-HA complex by receptor mediated endocytosis. Mol Pharm, 2009, 6(3):727-737.
43.	Kang Y, Zhang X, Jiang W, et al. Tumor-directed gene therapy in mice using a composite nonviral gene del ivery system consisting of the piggyBac transposon and polyethylenimine. BMC Cancer, 2009, 9: 126.
44.	Yang Y, Lo SL, Yang J, et al. Polyethylenimine coating to produce serum-resistant baculoviral vectors for in vivo gene delivery. Biomaterials, 2009, 30(29):5767-5774.
45.	Zamora-Avila DE, Zapata-Benavides P, Franco-Molina MA, et al. WT1 gene silencing by aerosol delivery of PEI-RNAi complexes inhibits B16-F10 lung metastases growth. Cancer Gene Ther, 2009, 16(12): 892-899.
46.	Siu KS, Chen D, Zheng X, et al. Non-covalently functionalized singlewalled carbon nanotube for topical siRNA del ivery into melanoma. Biomaterials, 2014, 35(10):3435-3442.
47.	Zhou Y, Wang H, Wang C, et al. Receptor-mediated, tumor-targeted gene del ivery using folate-terminated polyrotaxanes. Mol Pharm, 2012, 9(5):1067-1076.
48.	Gaspar HB, Bjorkegren E, Parsley K, et al. Successful reconstitution of immunity in ADA-SCID by stem cell gene therapy following cessation of PEG-ADA and use of mild preconditioning. Mol Ther, 2006, 14(4): 505-513.
49.	Collet G, Grillon C, Nadim M, et al. Trojan horse at cellular level for tumor gene therapies. Gene, 2013, 525(2):208-216.
50.	Shen J, Wang Q, Hu Q, et al. Restoration of chemosensitivity by multifunctional micelles mediated by P-gp siRNA to reverse MDR. Biomaterials, 2014, 35(30):8621-8634.

1. Bank A, Dorazio R, Leboulch P. A phase I/Ⅱ cl inical trial of beta-globin gene therapy for beta-thalassemia. Ann N Y Acad Sci, 2005, 1054: 308-316.
2. Pearson S, Jia H, Kandachi K. China approves first gene therapy. Nat Biotechnol, 2004, 22(1):3-4.
3. Kopatz I, Remy JS, Behr JP. A model for non-viral gene del ivery: through syndecan adhesion molecules and powered by actin. J Gene Med, 2004, 6(7):769-776.
4. Boussif O, Lezoualćh F, Zanta MA, et al. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo:polyethylenimine. Proc Natl Acad Sci U S A, 1995, 92(16):7297-7301.
5. Kunath K, von Harpe A, Fischer D, et al. Low-molecular-weight polyethylenimine as a non-viral vector for DNA del ivery:comparison of physicochemical properties, transfection efficiency and in vivo distribution with high-molecular-weight polyethylenimine. J Control Release, 2003, 89(1):113-125.
6. von Harpe A, Petersen H, Li Y, et al. Characterization of commercially available and synthesized polyethylenimines for gene delivery. J Control Release, 2000, 69(2):309-322.
7. Fischer D, Bieber T, Li Y, et al. A novel non-viral vector for DNA del ivery based on low molecular weight, branched polyethylenimine: effect of molecular weight on transfection efficiency and cytotoxicity. Pharm Res, 1999, 16(8):1273-1279.
8. Lungwitz U, Breunig M, Blunk T, et al. Polyethylenimine-based nonviral gene delivery systems. Eur J Pharm Biopharm, 2005, 60(2):247-266.
9. Zou SM, Erbacher P, Remy JS, et al. Systemic linear polyethylenimine (L-PEI)-mediated gene delivery in the mouse. J Gene Med, 2000, 2(2): 128-134.
10. Brunner S, Sauer T, Carotta S, et al. Cell cycle dependence of gene transfer by l i poplex, polyplex and recombinant adenovirus. Gene Ther, 2000, 7(5):401-407.
11. Brunner S, Fürtbauer E, Sauer T, et al. Overcoming the nuclear barrier: cell cycle independent nonviral gene transfer with linear polyethylenimine or electroporation. Mol Ther, 2002, 5(1):80-86.
12. Wightman L, Kircheis R, Rössler V, et al. Different behavior of branched and linear polyethylenimine for gene delivery in vitro and in vivo. J Gene Med, 2001, 3(4):362-372.
13. Goula D, Remy JS, Erbacher P, et al. Size, diffusibil ity and transfection performance of linear PEI/DNA complexes in the mouse central nervous system. Gene therapy, 1995, (5):712-717.
14. Rudolph C, Ortiz A, Schillinger U, et al. Methodological optimization of polyethylenimine (PEI)-based gene delivery to the lungs of mice via aerosol application. J Gene Med, 2005, 7(1):59-66.
15. Min SH, Lee DC, Lim MJ, et al. A composite gene delivery system consisting of polyethylenimine and an amphipathic peptide KALA. J Gene Med, 2006, 8(12):1425-1434.
16. Jeudy G, Salvadori F, Chauffert B, et al. Polyethylenimine-mediated in vivo gene transfer of a transmembrane superantigen fusion construct inhibits B16 murine melanoma growth. Cancer Gene Ther, 2008, 15(11):742-749.
17. Tada Y, Kitahara T, Yoshioka T, et al. Partial hepatectomy enhances polyethylenimine-mediated plasmid DNA del ivery. Biol Pharm Bull, 2006, 29(8):1712-1716.
18. Morille M, Passirani C, Vonarbourg A, et al. Progress in developing cationic vectors for non-viral systemic gene therapy against cancer. Biomaterials, 2008, 29(24-25):3477-3496.
19. Ogris M, Brunner S, Schüller S, et al. PEGylated DNA/transferrin-PEI complexes:reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery. Gene Ther, 1999, 6(4):595-605.
20. Mishra S, Webster P, Davis ME. PEGylation significantly affects cellular uptake and intracellular trafficking of non-viral gene del ivery particles. Eur J Cell Biol, 2004, 83(3):97-111.
21. Chen J, Gao X, Hu K, et al. Galactose-poly(ethylene glycol)-polyethylenimine for improved lung gene transfer. Biochem Biophysical Res Commun, 2008, 375(3):378-383.
22. Kleemann E, Neu M, Jekel N, et al. Nano-carriers for DNA del ivery to the lung based upon a TAT-derived peptide covalently coupled to PEG-PEI. J Control Release, 2005, 109(1-3):299-316.
23. Bivas-Benita M, Lin MY, Bal SM, et al. Pulmonary del ivery of DNA encoding Mycobacterium tuberculosis latency antigen Rv1733c associated to PLGA-PEI nanoparticles enhances T cell responses in a DNA prime/protein boost vaccination regimen in mice. Vaccine, 2009, 27(30):4010-4017.
24. Sasaki H, Yoshida S, Kitahara T, et al. Influence of disease stage on polyethylenimine-mediated plasmid DNA delivery in murine hepatitis. Int J Pharm, 2006, 318(1-2):139-145.
25. Liu Y, Tao J, Li Y, et al. Targeting hypoxia-inducible factor-1alpha with Tf-PEI-shRNA complex via transferrin receptor-mediated endocytosis inhibits melanoma growth. Mol Ther, 2009, 17(2):269-277.
26. Di Gioia S, Rejman J, Carrabino S, et al. Role of biophysical parameters on ex vivo and in vivo gene transfer to the airway epithelium by polyethylenimine/albumin complexes. Biomacromolecules, 2008, 9(3): 859-866.
27. Iwai M, Harada Y, Tanaka S, et al. Polyethylenimine-mediated suicide gene transfer induces a therapeutic effect for hepatocellular carcinoma in vivo by using an Epstein-Barr virus-based plasmid vector. Biochem Biophys Res Commun, 2002, 291(1):48-54.
28. Grosse S, Thevenot G, Aron Y, et al. In vivo gene delivery in the mouse lung with lactosylated polyethylenimine, questioning the relevance of in vitro experiments. J Control Release, 2008, 132(2):105-112.
29. Moffatt S, Wiehle S, Cristiano RJ. Tumor-specific gene delivery mediated by a novel peptide-polyethylenimine-DNA polyplex targeting aminopeptidase N/CD13. Hum Gene Ther, 2005, 16(1):57-67.
30. Huang YC, Riddle K, Rice KG, et al. Long-term in vivo gene expression via delivery of PEI-DNA condensates from porous polymer scaffolds. Hum Gene Ther, 2005, 16(5):609-617.
31. Kawazu T, Kanzaki H, Uno A, et al. HVJ-E/importin-β hybrid vector for overcoming cytoplasmic and nuclear membranes as double barrier for non-viral gene del ivery. Biomed Pharmacother, 2012, 66(7):519-524.
32. Liu Y, Steele T, Kissel T. Degradation of Hyper-Branched Poly(ethylenimine)-graft-poly(caprolactone)-block-monomethoxylpoly( ethylene glycol) as a Potential Gene Del ivery Vector. Macromol Rapid Commun, 2010, 31(17):1509-1515.
33. d'Ayala GG, Calarco A, Malinconico M, et al. Cationic copolymers nanoparticles for nonviral gene vectors:synthesis, characterization, and application in gene delivery. J Biomed Mater Res A, 2010, 94(2): 619-630.
34. Orsi S, De Capua A, Guarnieri D, et al. Cell recruitment and transfection in gene activated collagen matrix. Biomaterials, 2010, 31(3):570-576.
35. Mountziaris PM, Tzouanas SN, Sing DC, et al. Intra-articular controlled release of anti-inflammatory siRNA with biodegradable polymer microparticles ameliorates temporomandibular joint inflammation. Acta Biomater, 2012, 8(10):3552-3560.
36. Pi Y, Zhang X, Shi J, et al. Targeted delivery of non-viral vectors to cartilage in vivo using a chondrocyte-homing peptide identified by phage display. Biomaterials, 2011, 32(26):6324-6332.
37. Kuo CN, Yang LC, Wu PC, et al. Dehydrated form of plasmid expressing basic fibroblast growth factor-polyethylenimine complex is a novel and accurate method for gene transfer to the cornea. Curr Eye Res, 2005, 30(11):1015-1024.
38. Yuan J, Liu Y, Weilan H, et al. An experimental study on in situ transfection of the interleukin-1 receptor antagonist (IL-1ra) gene into the rat cornea. Curr Eye Res, 2012, 37(11):997-1004.
39. Zhou X, Liu B, Yu X, et al. Controlled release of PEI/DNA complexes from PLGA microspheres as a potent del ivery system to enhance immune response to HIV vaccine DNA prime/MVA boost regime. Eur J Pharm Biopharm, 2008, 68(3):589-595.
40. Zhou X, Liu B, Yu X, et al. Controlled release of PEI/DNA complexes from mannose-bearing chitosan microspheres as a potent del ivery system to enhance immune response to HBV DNA vaccine. J Control Release, 2007, 121(3):200-207.
41. Thomas M, Lu JJ, Ge Q, et al. Full deacylation of polyethylenimine dramatically boosts its gene delivery efficiency and specificity to mouse lung. Proc Natl Acad Sci U S A, 2005, 102(16):5679-5684.
42. Jiang G, Park K, Kim J, et al. Target specific intracellular del ivery of siRNA/PEI-HA complex by receptor mediated endocytosis. Mol Pharm, 2009, 6(3):727-737.
43. Kang Y, Zhang X, Jiang W, et al. Tumor-directed gene therapy in mice using a composite nonviral gene del ivery system consisting of the piggyBac transposon and polyethylenimine. BMC Cancer, 2009, 9: 126.
44. Yang Y, Lo SL, Yang J, et al. Polyethylenimine coating to produce serum-resistant baculoviral vectors for in vivo gene delivery. Biomaterials, 2009, 30(29):5767-5774.
45. Zamora-Avila DE, Zapata-Benavides P, Franco-Molina MA, et al. WT1 gene silencing by aerosol delivery of PEI-RNAi complexes inhibits B16-F10 lung metastases growth. Cancer Gene Ther, 2009, 16(12): 892-899.
46. Siu KS, Chen D, Zheng X, et al. Non-covalently functionalized singlewalled carbon nanotube for topical siRNA del ivery into melanoma. Biomaterials, 2014, 35(10):3435-3442.
47. Zhou Y, Wang H, Wang C, et al. Receptor-mediated, tumor-targeted gene del ivery using folate-terminated polyrotaxanes. Mol Pharm, 2012, 9(5):1067-1076.
48. Gaspar HB, Bjorkegren E, Parsley K, et al. Successful reconstitution of immunity in ADA-SCID by stem cell gene therapy following cessation of PEG-ADA and use of mild preconditioning. Mol Ther, 2006, 14(4): 505-513.
49. Collet G, Grillon C, Nadim M, et al. Trojan horse at cellular level for tumor gene therapies. Gene, 2013, 525(2):208-216.
50. Shen J, Wang Q, Hu Q, et al. Restoration of chemosensitivity by multifunctional micelles mediated by P-gp siRNA to reverse MDR. Biomaterials, 2014, 35(30):8621-8634.

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RESEARCH PROGRESS OF IN VIVO NUCLEIC ACID DELIVERY WITH POLY (ETHYLENIMINE)

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