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Engineered DNA plasmid reduces immunity to dystrophin while improving muscle force in a model of gene therapy of Duchenne dystrophy.

التفاصيل البيبلوغرافية
العنوان: Engineered DNA plasmid reduces immunity to dystrophin while improving muscle force in a model of gene therapy of Duchenne dystrophy.
المؤلفون: Ho PP; Department of Neurology, Stanford University, Stanford, CA 94304., Lahey LJ; Department of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, CA 94304.; Department of Medicine, Division of Immunology and Rheumatology, Veteran Affairs Palo Alto Health Care System, Palo Alto, CA 94304., Mourkioti F; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305., Kraft PE; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305., Filareto A; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305., Brandt M; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305., Magnusson KEG; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305., Finn EE; Department of Neurology, Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Washington, Seattle, WA 98195.; Department of Medicine, Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Washington, Seattle, WA 98195.; Department of Biochemistry, Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Washington, Seattle, WA 98195., Chamberlain JS; Department of Neurology, Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Washington, Seattle, WA 98195.; Department of Medicine, Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Washington, Seattle, WA 98195.; Department of Biochemistry, Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Washington, Seattle, WA 98195., Robinson WH; Department of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, CA 94304.; Department of Medicine, Division of Immunology and Rheumatology, Veteran Affairs Palo Alto Health Care System, Palo Alto, CA 94304., Blau HM; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305., Steinman L; Department of Neurology, Stanford University, Stanford, CA 94304; steinman@stanford.edu.
المصدر: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2018 Sep 25; Vol. 115 (39), pp. E9182-E9191. Date of Electronic Publication: 2018 Sep 04.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : National Academy of Sciences
مواضيع طبية MeSH: DNA*/genetics , DNA*/pharmacokinetics , Genetic Vectors*/pharmacology , Plasmids*/genetics , Plasmids*/pharmacology, Dependovirus/*genetics , Genetic Therapy/*methods , Muscle Strength/*genetics , Muscular Dystrophy, Duchenne/*therapy, Animals ; Disease Models, Animal ; Dystrophin/genetics ; Dystrophin/immunology ; Dystrophin/metabolism ; Male ; Mice ; Mice, Inbred mdx ; Muscle Strength/immunology ; Muscular Dystrophy, Duchenne/genetics ; Muscular Dystrophy, Duchenne/immunology ; Muscular Dystrophy, Duchenne/metabolism
مستخلص: In gene therapy for Duchenne muscular dystrophy there are two potential immunological obstacles. An individual with Duchenne muscular dystrophy has a genetic mutation in dystrophin, and therefore the wild-type protein is "foreign," and thus potentially immunogenic. The adeno-associated virus serotype-6 (AAV6) vector for delivery of dystrophin is a viral-derived vector with its own inherent immunogenicity. We have developed a technology where an engineered plasmid DNA is delivered to reduce autoimmunity. We have taken this approach into humans, tolerizing to myelin proteins in multiple sclerosis and to proinsulin in type 1 diabetes. Here, we extend this technology to a model of gene therapy to reduce the immunogenicity of the AAV vector and of the wild-type protein product that is missing in the genetic disease. Following gene therapy with systemic administration of recombinant AAV6-microdystrophin to mdx/mTR G2 mice, we demonstrated the development of antibodies targeting dystrophin and AAV6 capsid in control mice. Treatment with the engineered DNA construct encoding microdystrophin markedly reduced antibody responses to dystrophin and to AAV6. Muscle force in the treated mice was also improved compared with control mice. These data highlight the potential benefits of administration of an engineered DNA plasmid encoding the delivered protein to overcome critical barriers in gene therapy to achieve optimal functional gene expression.
Competing Interests: Conflict of interest statement: Stanford University has filed a provisional patent application on behalf of P.P.H. and L.S. claiming some of the concepts contemplated in this publication. L.S. and Reinhard Hohlfeld are coauthors on a 2017 Commentary.
التعليقات: Comment in: Proc Natl Acad Sci U S A. 2018 Sep 25;115(39):9652-9654. (PMID: 30190431)
References: Expert Opin Orphan Drugs. 2015;3(11):1255-1266. (PMID: 26594599)
Biochim Biophys Acta. 2007 Feb;1772(2):243-62. (PMID: 17064882)
J Virol. 2000 Mar;74(5):2420-5. (PMID: 10666273)
Science. 2016 Jan 22;351(6271):403-7. (PMID: 26721684)
Neuron. 1989 Jan;2(1):1019-29. (PMID: 2696500)
Hum Gene Ther. 2017 Nov;28(11):1061-1074. (PMID: 28835127)
Pediatr Cardiol. 2012 Oct;33(7):1175-9. (PMID: 22434508)
FEBS Lett. 1998 Mar 27;425(2):329-36. (PMID: 9559674)
Muscle Nerve. 1997 Apr;20(4):469-78. (PMID: 9121505)
Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8. (PMID: 9843981)
Hum Gene Ther. 2007 Jan;18(1):18-26. (PMID: 17176210)
J Immunol. 2003 Nov 1;171(9):4920-6. (PMID: 14568974)
N Engl J Med. 1995 Sep 28;333(13):832-8. (PMID: 7651473)
Sci Transl Med. 2013 Jun 26;5(191):191ra82. (PMID: 23803704)
Nat Med. 1999 Jan;5(1):64-70. (PMID: 9883841)
Cell. 1987 Jul 31;50(3):509-17. (PMID: 3607877)
Nat Med. 1997 Sep;3(9):970-7. (PMID: 9288722)
Genomics. 1988 Jan;2(1):90-5. (PMID: 3384440)
Hum Mol Genet. 1995 Aug;4(8):1251-8. (PMID: 7581361)
Ann Neurol. 2012 Mar;71(3):304-13. (PMID: 22451200)
Ann Neurol. 2008 May;63(5):611-20. (PMID: 18481290)
Mol Ther. 2000 Feb;1(2):154-8. (PMID: 10933925)
Ann Neurol. 1993 Jul;34(1):8-17. (PMID: 8517684)
Nat Commun. 2015 Feb 18;6:6244. (PMID: 25692716)
J Neurol Sci. 1991 Apr;102(2):190-6. (PMID: 2072118)
Mol Ther. 2008 Apr;16(4):657-64. (PMID: 18334986)
J Neurol Sci. 1978 May;36(3):349-62. (PMID: 681967)
Nat Cell Biol. 2013 Aug;15(8):895-904. (PMID: 23831727)
Nat Med. 2002 Mar;8(3):253-61. (PMID: 11875496)
Am J Pathol. 1989 Jul;135(1):27-32. (PMID: 2672825)
Arch Neurol. 2007 Oct;64(10):1407-15. (PMID: 17698695)
Nature. 1989 Jan 12;337(6203):176-9. (PMID: 2643055)
Nucleic Acids Res. 1992 Apr 11;20(7):1725-31. (PMID: 1579466)
Neuromuscul Disord. 2002 Dec;12(10):926-9. (PMID: 12467747)
Mol Ther. 2014 Feb;22(2):338-347. (PMID: 24196577)
Nature. 1987 Jul 9-15;328(6126):166-8. (PMID: 3600793)
Sci Transl Med. 2017 Nov 29;9(418):null. (PMID: 29187645)
N Engl J Med. 2010 Oct 7;363(15):1429-37. (PMID: 20925545)
Cell. 2010 Dec 23;143(7):1059-71. (PMID: 21145579)
Mol Ther. 2001 Dec;4(6):525-33. (PMID: 11735336)
J Intern Med. 2010 May;267(5):441-51. (PMID: 20433574)
Cardiology. 2003;99(1):1-19. (PMID: 12589117)
Nat Biotechnol. 2003 Sep;21(9):1033-9. (PMID: 12910246)
Mol Ther. 2007 Jun;15(6):1160-6. (PMID: 17426713)
Nat Commun. 2013;4:1549. (PMID: 23462992)
Am Heart J. 1994 Mar;127(3):618-23. (PMID: 8122611)
Nat Med. 2004 Aug;10(8):828-34. (PMID: 15273747)
Nature. 1990 Jan 11;343(6254):180-2. (PMID: 2404210)
J Hum Genet. 2017 Oct;62(10):871-876. (PMID: 28566768)
Mol Ther. 2017 May 3;25(5):1125-1131. (PMID: 28416280)
Stem Cells. 2014 Jul;32(7):1817-30. (PMID: 24753122)
Science. 2016 Jan 22;351(6271):400-3. (PMID: 26721683)
PLoS Genet. 2010 May 20;6(5):e1000958. (PMID: 20502633)
Mol Ther. 2005 Dec;12(6):1023-33. (PMID: 16263332)
Hum Mol Genet. 2010 Aug 15;19(16):3266-81. (PMID: 20542988)
Pediatr Ann. 2005 Jul;34(7):525-30. (PMID: 16092626)
Hum Genet. 1984;66(1):17-40. (PMID: 6365739)
Am J Hum Genet. 1992 May;50(5):950-9. (PMID: 1570844)
J Neurol Sci. 1990 Oct;99(1):9-25. (PMID: 2250176)
Clin Immunol. 2013 Dec;149(3):297-306. (PMID: 24094739)
Nat Med. 2006 Mar;12(3):342-7. (PMID: 16474400)
Immunity. 2001 Jul;15(1):15-22. (PMID: 11485734)
Nature. 1992 Apr 2;356(6368):435-8. (PMID: 1557125)
Muscle Nerve. 2013 May;47(5):649-63. (PMID: 23553671)
Curr Top Dev Biol. 2005;68:263-80. (PMID: 16125002)
Nat Genet. 1993 Apr;3(4):283-91. (PMID: 7981747)
Gene Ther. 2000 Sep;7(17):1447-57. (PMID: 11001364)
Nat Med. 2006 Jul;12(7):787-9. (PMID: 16819550)
Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21. (PMID: 11309499)
Vaccine. 2009 Jan 29;27(5):690-700. (PMID: 19095031)
Nat Commun. 2017 Feb 14;8:14454. (PMID: 28195574)
Nat Biotechnol. 2005 Nov;23(11):1435-9. (PMID: 16244658)
NPJ Regen Med. 2018 Feb 16;3:4. (PMID: 29479480)
Proc Natl Acad Sci U S A. 1984 Feb;81(4):1189-92. (PMID: 6583703)
Science. 2016 Jan 22;351(6271):407-411. (PMID: 26721686)
J Immunol. 2008 Dec 15;181(12):8298-307. (PMID: 19050246)
Gene Ther. 2004 Jun;11(11):884-93. (PMID: 14985788)
Gene Ther. 2002 Dec;9(23):1576-88. (PMID: 12424610)
معلومات مُعتمدة: P50 AR065139 United States AR NIAMS NIH HHS; R01 AR040864 United States AR NIAMS NIH HHS; R01 HL122332 United States HL NHLBI NIH HHS; U54 HD083091 United States HD NICHD NIH HHS
فهرسة مساهمة: Keywords: DNA plasmid; Duchenne muscular dystrophy; gene replacement therapy; mdx/mTRG2 mice; microdystrophin
المشرفين على المادة: 0 (Dystrophin)
0 (apo-dystrophin 1)
9007-49-2 (DNA)
تواريخ الأحداث: Date Created: 20180906 Date Completed: 20181016 Latest Revision: 20220924
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC6166850
DOI: 10.1073/pnas.1808648115
PMID: 30181272
قاعدة البيانات: MEDLINE
الوصف
تدمد:1091-6490
DOI:10.1073/pnas.1808648115