Immunosuppression overcomes insulin- and vector-specific immune responses that limit efficacy of AAV2/8-mediated insulin gene therapy in NOD mice.
Animals
CD4 Antigens
/ immunology
Dependovirus
/ genetics
Diabetes Mellitus, Experimental
/ therapy
Genetic Therapy
/ adverse effects
HEK293 Cells
Humans
Immunosuppression Therapy
/ methods
Insulin
/ genetics
Liver
/ immunology
Male
Mice
Mice, Inbred C57BL
Mice, Inbred NOD
Mice, SCID
T-Lymphocytes
/ immunology
Journal
Gene therapy
ISSN: 1476-5462
Titre abrégé: Gene Ther
Pays: England
ID NLM: 9421525
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
06
08
2018
accepted:
06
11
2018
revised:
09
10
2018
pubmed:
6
12
2018
medline:
12
4
2019
entrez:
6
12
2018
Statut:
ppublish
Résumé
We report the restoration of euglycaemia in chemically induced diabetic C57BL/6 mice and spontaneously diabetic Non Obese Diabetic (NOD) mice by intravenous systemic administration of a single-stranded adeno-associated virus (ssAAV2/8) codon optimised (co) vector encoding furin cleavable human proinsulin under a liver-specific promoter. There were no immunological barriers to efficacy of insulin gene therapy in chemically induced C57BL/6 mice, which enjoyed long-lasting correction of hyperglycaemia after therapy, up to 250 days. Euglycaemia was also restored in spontaneously diabetic NOD mice, although these mice required a 7-10-fold higher dose of vector to achieve similar efficacy as the C57BL/6 mice and the immunodeficient NOD
Identifiants
pubmed: 30514969
doi: 10.1038/s41434-018-0052-5
pii: 10.1038/s41434-018-0052-5
pmc: PMC6514884
doi:
Substances chimiques
CD4 Antigens
0
Insulin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
40-56Subventions
Organisme : National Centre for the Replacement, Refinement and Reduction of Animals in Research
ID : NC/M001083/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L013185/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0902219
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 106 263/Z/14/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 106262/Z/14/Z
Pays : United Kingdom
Organisme : Department of Health
ID : RP-PG-0310-1001
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M009041/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12012/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M024873/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12012/5
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12012/3
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00014/3
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0502121
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00014/5
Pays : United Kingdom
Références
Hum Gene Ther. 1999 Jul 20;10(11):1753-62
pubmed: 10446915
Nat Med. 1999 Sep;5(9):1026-31
pubmed: 10470079
Int Immunol. 1999 Oct;11(10):1685-91
pubmed: 10508186
Science. 2000 Feb 4;287(5454):826-30
pubmed: 10657290
Curr Biol. 2000 Feb 24;10(4):227-30
pubmed: 10704418
Eur J Immunol. 2002 Feb;32(2):333-40
pubmed: 11807772
Transplantation. 2002 Sep 15;74(5):611-9
pubmed: 12352875
Transplantation. 2002 Dec 27;74(12):1781-7
pubmed: 12499898
Blood. 2003 Jul 15;102(2):480-8
pubmed: 12637328
J Clin Invest. 2003 May;111(9):1347-56
pubmed: 12727926
J Gene Med. 2003 May;5(5):425-37
pubmed: 12731091
Hum Gene Ther. 2003 Oct 10;14(15):1401-13
pubmed: 14577921
Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2112-6
pubmed: 14766968
J Gene Med. 2005 May;7(5):621-9
pubmed: 15651056
Hepatology. 2005 Jul;42(1):193-9
pubmed: 15962311
Mol Ther. 2005 Dec;12(6):1023-33
pubmed: 16263332
Eur J Immunol. 2008 Jan;38(1):240-9
pubmed: 18157812
J Clin Invest. 2008 Oct;118(10):3390-402
pubmed: 18802479
Annu Rev Immunol. 2009;27:147-63
pubmed: 19302037
Hepatology. 2009 Aug;50(2):612-21
pubmed: 19575456
Rev Diabet Stud. 2009;6(2):97-103
pubmed: 19806239
Blood. 2010 Feb 11;115(6):1145-55
pubmed: 20007541
Can Med Assoc J. 1922 Mar;12(3):141-6
pubmed: 20314060
Gene Ther. 2012 Jan;19(1):78-85
pubmed: 21716299
N Engl J Med. 2011 Dec 22;365(25):2357-65
pubmed: 22149959
Elife. 2012 Dec 18;1:e00047
pubmed: 23251783
Diabetes. 2013 May;62(5):1718-29
pubmed: 23378612
Diabetes. 2013 Sep;62(9):3132-42
pubmed: 23715623
PLoS One. 2013 Jun 27;8(6):e67515
pubmed: 23826312
Trends Immunol. 2013 Dec;34(12):583-91
pubmed: 24054837
N Engl J Med. 2014 Nov 20;371(21):1994-2004
pubmed: 25409372
Exp Clin Transplant. 2015 Apr;13 Suppl 1:37-45
pubmed: 25894126
Sci Transl Med. 2015 May 27;7(289):289ra81
pubmed: 26019217
J Gene Med. 2015 Aug-Sep;17(8-9):141-52
pubmed: 26190010
Hum Gene Ther. 2015 Nov;26(11):743-50
pubmed: 26417913
Curr Gene Ther. 2016;16(1):65-72
pubmed: 26795016
Kidney Int. 2016 Apr;89(4):909-17
pubmed: 26924059
J Exp Med. 2016 Jun 27;213(7):1223-39
pubmed: 27325889
J Gene Med. 2016 Oct;18(10):312-321
pubmed: 27572655
N Engl J Med. 2017 Mar 2;376(9):848-855
pubmed: 28249145
BMJ Open. 2017 Mar 22;7(3):e012567
pubmed: 28336735
Mol Metab. 2017 May 17;6(7):664-680
pubmed: 28702323
PLoS One. 2017 Aug 3;12(8):e0181964
pubmed: 28771521
Biosci Rep. 2017 Aug 30;37(4):null
pubmed: 28798194
Annu Rev Virol. 2017 Sep 29;4(1):511-534
pubmed: 28961410
N Engl J Med. 2017 Dec 28;377(26):2519-2530
pubmed: 29224506
N Engl J Med. 2018 Apr 19;378(16):1479-1493
pubmed: 29669226
Rapid Commun Mass Spectrom. 2018 Aug 30;32(16):1414-1424
pubmed: 29857350
Front Immunol. 2018 May 18;9:1006
pubmed: 29867981
Trans Assoc Am Physicians. 1984;97:80-7
pubmed: 6398950
Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3293-7
pubmed: 7724555
Diabetes Res Clin Pract. 1994 Oct;24 Suppl:S153-7
pubmed: 7859599
Cell. 1995 Mar 10;80(5):813-23
pubmed: 7889575