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The genome of self-complementary adeno-associated viral vectors increases Toll-like receptor 9-dependent innate immune responses in the liver.

Martino AT, Suzuki M, Markusic DM, Zolotukhin I, Ryals RC, Moghimi B, Ertl HC, Muruve DA, Lee B, Herzog RW.

Blood. 2011 Jun 16;117(24):6459-68. doi: 10.1182/blood-2010-10-314518. Epub 2011 Apr 7.


The TLR9-MyD88 pathway is critical for adaptive immune responses to adeno-associated virus gene therapy vectors in mice.

Zhu J, Huang X, Yang Y.

J Clin Invest. 2009 Aug;119(8):2388-98. doi: 10.1172/JCI37607. Epub 2009 Jul 1.


Enhancing transduction of the liver by adeno-associated viral vectors.

Nathwani AC, Cochrane M, McIntosh J, Ng CY, Zhou J, Gray JT, Davidoff AM.

Gene Ther. 2009 Jan;16(1):60-9. doi: 10.1038/gt.2008.137. Epub 2008 Aug 14.


Toll-like receptor 2-mediated innate immune response in human nonparenchymal liver cells toward adeno-associated viral vectors.

Hösel M, Broxtermann M, Janicki H, Esser K, Arzberger S, Hartmann P, Gillen S, Kleeff J, Stabenow D, Odenthal M, Knolle P, Hallek M, Protzer U, Büning H.

Hepatology. 2012 Jan;55(1):287-97. doi: 10.1002/hep.24625.


CpG-depleted adeno-associated virus vectors evade immune detection.

Faust SM, Bell P, Cutler BJ, Ashley SN, Zhu Y, Rabinowitz JE, Wilson JM.

J Clin Invest. 2013 Jul;123(7):2994-3001. doi: 10.1172/JCI68205. Epub 2013 Jun 17.


Adenovirus vector-induced innate inflammatory mediators, MAPK signaling, as well as adaptive immune responses are dependent upon both TLR2 and TLR9 in vivo.

Appledorn DM, Patial S, McBride A, Godbehere S, Van Rooijen N, Parameswaran N, Amalfitano A.

J Immunol. 2008 Aug 1;181(3):2134-44.


Self-complementary AAVs induce more potent transgene product-specific immune responses compared to a single-stranded genome.

Wu T, Töpfer K, Lin SW, Li H, Bian A, Zhou XY, High KA, Ertl HC.

Mol Ther. 2012 Mar;20(3):572-9. doi: 10.1038/mt.2011.280. Epub 2011 Dec 20.


Unique Roles of TLR9- and MyD88-Dependent and -Independent Pathways in Adaptive Immune Responses to AAV-Mediated Gene Transfer.

Rogers GL, Suzuki M, Zolotukhin I, Markusic DM, Morel LM, Lee B, Ertl HC, Herzog RW.

J Innate Immun. 2015;7(3):302-14. doi: 10.1159/000369273. Epub 2015 Jan 20.


Optimized adeno-associated virus (AAV)-protein phosphatase-5 helper viruses for efficient liver transduction by single-stranded AAV vectors: therapeutic expression of factor IX at reduced vector doses.

Jayandharan GR, Zhong L, Sack BK, Rivers AE, Li M, Li B, Herzog RW, Srivastava A.

Hum Gene Ther. 2010 Mar;21(3):271-83. doi: 10.1089/hum.2009.100.


Self-complementary adeno-associated virus vectors containing a novel liver-specific human factor IX expression cassette enable highly efficient transduction of murine and nonhuman primate liver.

Nathwani AC, Gray JT, Ng CY, Zhou J, Spence Y, Waddington SN, Tuddenham EG, Kemball-Cook G, McIntosh J, Boon-Spijker M, Mertens K, Davidoff AM.

Blood. 2006 Apr 1;107(7):2653-61. Epub 2005 Dec 1.


IL12-mediated liver inflammation reduces the formation of AAV transcriptionally active forms but has no effect over preexisting AAV transgene expression.

Gil-Fariña I, Di Scala M, Vanrell L, Olagüe C, Vales A, High KA, Prieto J, Mingozzi F, Gonzalez-Aseguinolaza G.

PLoS One. 2013 Jul 2;8(7):e67748. doi: 10.1371/journal.pone.0067748. Print 2013.


Differential activation of innate immune responses by adenovirus and adeno-associated virus vectors.

Zaiss AK, Liu Q, Bowen GP, Wong NC, Bartlett JS, Muruve DA.

J Virol. 2002 May;76(9):4580-90.


Synergistic inhibition of PARP-1 and NF-κB signaling downregulates immune response against recombinant AAV2 vectors during hepatic gene therapy.

Hareendran S, Ramakrishna B, Jayandharan GR.

Eur J Immunol. 2016 Jan;46(1):154-66. doi: 10.1002/eji.201545867. Epub 2015 Nov 5.


Strategies for improving the transduction efficiency of single-stranded adeno-associated virus vectors in vitro and in vivo.

Jayandharan GR, Zhong L, Li B, Kachniarz B, Srivastava A.

Gene Ther. 2008 Sep;15(18):1287-93. doi: 10.1038/gt.2008.89. Epub 2008 May 22.


Role of the vector genome and underlying factor IX mutation in immune responses to AAV gene therapy for hemophilia B.

Rogers GL, Martino AT, Zolotukhin I, Ertl HC, Herzog RW.

J Transl Med. 2014 Jan 25;12:25. doi: 10.1186/1479-5876-12-25.


Immune responses to AAV in clinical trials.

Mingozzi F, High KA.

Curr Gene Ther. 2007 Oct;7(5):316-24. Review.


Adeno-associated virus capsid structure drives CD4-dependent CD8+ T cell response to vector encoded proteins.

Mays LE, Vandenberghe LH, Xiao R, Bell P, Nam HJ, Agbandje-McKenna M, Wilson JM.

J Immunol. 2009 May 15;182(10):6051-60. doi: 10.4049/jimmunol.0803965.


Successful attenuation of humoral immunity to viral capsid and transgenic protein following AAV-mediated gene transfer with a non-depleting CD4 antibody and cyclosporine.

McIntosh JH, Cochrane M, Cobbold S, Waldmann H, Nathwani SA, Davidoff AM, Nathwani AC.

Gene Ther. 2012 Jan;19(1):78-85. doi: 10.1038/gt.2011.64. Epub 2011 Jun 30.


Activation of the cellular unfolded protein response by recombinant adeno-associated virus vectors.

Balakrishnan B, Sen D, Hareendran S, Roshini V, David S, Srivastava A, Jayandharan GR.

PLoS One. 2013;8(1):e53845. doi: 10.1371/journal.pone.0053845. Epub 2013 Jan 8.

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