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Immune profiling of adeno-associated virus response identifies B cell-specific targets that enable vector re-administration in mice

Gene Therapy volume 30, pages 429–442 (2023)Cite this article

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Abstract

Adeno-associated virus (AAV) vector-based gene therapies can be applied to a wide range of diseases. AAV expression can last for months to years, but vector re-administration may be necessary to achieve life-long treatment. Unfortunately, immune responses against these vectors are potentiated after the first administration, preventing the clinical use of repeated administration of AAVs. Reducing the immune response against AAVs while minimizing broad immunosuppression would improve gene delivery efficiency and long-term safety. In this study, we quantified the contributions of multiple immune system components of the anti-AAV response in mice. We identified B-cell-mediated immunity as a critical component preventing vector re-administration. Additionally, we found that IgG depletion alone was insufficient to enable re-administration, suggesting IgM antibodies play an important role in the immune response against AAV. Further, we found that AAV-mediated transduction is improved in µMT mice that lack functional IgM heavy chains and cannot form mature B-cells relative to wild-type mice. Combined, our results suggest that B-cells, including non-class switched B-cells, are a potential target for therapeutics enabling AAV re-administration. Our results also suggest that the µMT mice are a potentially useful experimental model for gene delivery studies since they allow repeated dosing for more efficient gene delivery from AAVs.

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Fig. 1: Re-administration of AAV in the panel of immune-deficient mice.
Fig. 2: Neutralizing, IgM, and IgG antibody profiles after single and double injection.
Fig. 3: Biodistribution of single and double AAV administrations in WT mice.
Fig. 4: Re-administration of AAV does not alter splenic immune composition.
Fig. 5: Antibody cocktail depletion of B- and T-Cells in C57BL/6 mice.
Fig. 6: Re-administration of CAG-NLS-GFP PHP.eB to the brain.

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Data availability

The main data of this study are available within this published article and its supplementary information file. The raw and analyzed datasets generated during the study are available for research purposes from the corresponding author on reasonable request. scRNA-seq data have been deposited in the Gene Expression Omnibus (GEO) database, with series accession number GSE200223.

References

  1. Smalley E. First AAV gene therapy poised for landmark approval. Nat Biotechnol. 2017;35:998–9.

    Article  CAS  PubMed  Google Scholar 

  2. Li C, Samulski RJ. Engineering adeno-associated virus vectors for gene therapy. Nat Rev Genet. 2020;21:255–72.

    Article  CAS  PubMed  Google Scholar 

  3. Manno CS, Glenn FP, Arruda VR, Pierce GF, Glader B, Ragni M, et al. Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat Med. 2006;12:342–7.

    Article  CAS  PubMed  Google Scholar 

  4. Boutin S, Monteilhet V, Veron P, Leborgne C, Benveniste O, Montus MF, et al. Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV) types 1, 2, 5, 6, 8, and 9 in the healthy population: implications for gene therapy using AAV vectors. Hum Gene Ther. 2010;21:704–12.

    Article  CAS  PubMed  Google Scholar 

  5. Calcedo R, Vandenberghe Luk H, Gao G, Lin J, Wilson, James M. Worldwide epidemiology of neutralizing antibodies to adeno‐associated viruses. J Infectious Dis. 2009;199:381–90.

    Article  Google Scholar 

  6. Calcedo R, Morizono H, Wang L, McCarter R, He J, Jones D, et al. Adeno-associated virus antibody profiles in newborns, children, and adolescents. Clin Vaccine Immunol. 2011;18:1586–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Erles K, Sebökovà P, Schlehofer JR. Update on the prevalence of serum antibodies (IgG and IgM) to adeno‐associated virus (AAV). J Med Virol. 1999;59:406–11.

    Article  CAS  PubMed  Google Scholar 

  8. Kruzik A, Fetahagic D, Hartlieb B, Dorn S, Koppensteiner H, Horling FM, et al. Prevalence of anti-adeno-associated virus immune responses in international cohorts of healthy donors. Mol Ther Methods Clin Dev. 2019;14:126–33.

  9. Leborgne C, Latournerie V, Boutin S, Desgue D, Quéré A, Pignot E, et al. Prevalence and long-term monitoring of humoral immunity against adeno-associated virus in Duchenne Muscular Dystrophy patients. Cell Immunol. 2019;342:103780.

  10. Liu Q, Huang W, Zhang H, Wang Y, Zhao J, Song A, et al. Neutralizing antibodies against AAV2, AAV5 and AAV8 in healthy and HIV-1-infected subjects in China: implications for gene therapy using AAV vectors. Gene Ther. 2014;21:732–8.

    Article  CAS  PubMed  Google Scholar 

  11. George LA, Sullivan SK, Giermasz A, Rasko JEJ, Samelson-Jones BJ, Ducore J, et al. Hemophilia B gene therapy with a high-specific-activity factor IX variant. N Engl J Med. 2017;377:2215–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Rabinowitz J, Chan YK, Samulski RJ. Adeno-associated virus (AAV) versus immune response. Viruses. 2019;11:102.

  13. Tse LV, Klinc KA, Madigan VJ, Castellanos Rivera RM, Wells LF, Havlik LP, et al. Structure-guided evolution of antigenically distinct adeno-associated virus variants for immune evasion. Proc Natl Acad Sci. 2017;114:E4812–E21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. George LA, Ragni MV, Rasko JEJ, Raffini LJ, Samelson-Jones BJ, Ozelo M, et al. Long-term follow-up of the first in human intravascular delivery of AAV for gene transfer: AAV2-hFIX16 for severe hemophilia B. Mol Ther. 2020;28:2073–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Nathwani AC, Reiss UM, Tuddenham EGD, Rosales C, Chowdary P, McIntosh J, et al. Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med. 2014;371:1994–2004.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Rangarajan S, Walsh L, Lester W, Perry D, Madan B, Laffan M, et al. AAV5–Factor VIII gene transfer in severe hemophilia A. N Engl J Med. 2017;377:2519–30.

    Article  CAS  PubMed  Google Scholar 

  17. Weber T. Anti-AAV Antibodies in AAV Gene Therapy: Current Challenges and Possible Solutions. Front Immunol. 2021;12:658399.

  18. Meliani A, Boisgerault F, Hardet R, Marmier S, Collaud F, Ronzitti G, et al. Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration. Nat Commun. 2018;9:4098.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Calcedo R, Wilson J. Humoral immune response to AAV. Front Immunol. 2013;4:341.

  20. Duan D, Sharma P, Yang J, Yue Y, Dudus L, Zhang Y, et al. Circular intermediates of recombinant adeno-associated virus have defined structural characteristics responsible for long-term episomal persistence in muscle tissue. J Virol. 1998;72:8568–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Schnepp BC, Clark KR, Klemanski DL, Pacak CA, Johnson PR. Genetic fate of recombinant adeno-associated virus vector genomes in muscle. J Virol. 2003;77:3495–504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Schnepp BC, Jensen RL, Chen C-L, Johnson PR, Clark KR. Characterization of adeno-associated virus genomes isolated from human tissues. J Virol. 2005;79:14793–803.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Naso MF, Tomkowicz B, Perry WL, Strohl WR. Adeno-associated virus (AAV) as a vector for gene therapy. BioDrugs. 2017;31:317–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Wang L, Wang H, Bell P, McMenamin D, Wilson JM. Hepatic gene transfer in neonatal mice by adeno-associated virus serotype 8 vector. Hum Gene Ther. 2012;23:533–9.

    Article  CAS  PubMed  Google Scholar 

  25. Pasi KJ, Rangarajan S, Mitchell N, Lester W, Symington E, Madan B, et al. Multiyear follow-up of AAV5-hFVIII-SQ gene therapy for hemophilia A. N Engl J Med. 2020;382:29–40.

    Article  CAS  PubMed  Google Scholar 

  26. Colella P, Ronzitti G, Mingozzi F. Emerging issues in AAV-mediated in vivo gene therapy. Mol Ther Methods Clin Dev. 2018;8:87–104.

    Article  CAS  PubMed  Google Scholar 

  27. Muhuri M, Maeda Y, Ma H, Ram S, Fitzgerald KA, Tai PWL, et al. Overcoming innate immune barriers that impede AAV gene therapy vectors. J Clin Invest. 2021;131:e143780.

  28. Eixarch H, Gómez A, Kádár E, George M, Martínez N, Espejo C, et al. Transgene expression levels determine the immunogenicity of transduced hematopoietic grafts in partially myeloablated mice. Mol Ther. 2009;17:1904–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sargent D, Bétemps D, Drouyer M, Verchere J, Gaillard D, Arsac J-N, et al. Investigating the neuroprotective effect of AAV-mediated β-synuclein overexpression in a transgenic model of synucleinopathy. Sci Rep. 2018;8:17563.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Ronzitti G, Gross D-A, Mingozzi F. Human immune responses to adeno-associated virus (AAV) vectors. Front Immunol. 2020;11:670.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Zaiss AK, Liu Q, Bowen GP, Wong NCW, Bartlett JS, Muruve DA. Differential activation of innate immune responses by adenovirus and adeno-associated virus vectors. J Virol. 2002;76:4580–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Verdera HC, Kuranda K, Mingozzi F. AAV vector immunogenicity in humans: a long journey to successful gene transfer. Mol Ther. 2020;28:723–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ashley SN, Somanathan S, Giles AR, Wilson JM. TLR9 signaling mediates adaptive immunity following systemic AAV gene therapy. Cell Immunol. 2019;346:103997.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Rogers GL, Suzuki M, Zolotukhin I, Markusic DM, Morel LM, Lee B, et al. Unique roles of TLR9- and MyD88-dependent and -independent pathways in adaptive immune responses to AAV-mediated gene transfer. J Innate Immun. 2015;7:302–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Sudres M, Ciré S, Vasseur V, Brault L, Da Rocha S, Boisgérault F, et al. MyD88 signaling in B cells regulates the production of Th1-dependent antibodies to AAV. Mol Ther. 2012;20:1571–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Zhu J, Huang X, Yang Y. The TLR9-MyD88 pathway is critical for adaptive immune responses to adeno-associated virus gene therapy vectors in mice. J Clin Invest. 2009;119:2388–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zaiss AK, Cotter MJ, White LR, Clark SA, Wong NCW, Holers VM, et al. Complement is an essential component of the immune response to adeno-associated virus vectors. J Virol. 2008;82:2727–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Hui DJ, Edmonson SC, Podsakoff GM, Pien GC, Ivanciu L, Camire RM, et al. AAV capsid CD8+ T-cell epitopes are highly conserved across AAV serotypes. Mol Ther Methods Clin Dev. 2015;2:15029.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Mingozzi F, Maus MV, Hui DJ, Sabatino DE, Murphy SL, Rasko JEJ, et al. CD8+ T-cell responses to adeno-associated virus capsid in humans. Nat Med. 2007;13:419–22.

    Article  CAS  PubMed  Google Scholar 

  40. Pien GC, Basner-Tschakarjan E, Hui DJ, Mentlik AN, Finn JD, Hasbrouck NC, et al. Capsid antigen presentation flags human hepatocytes for destruction after transduction by adeno-associated viral vectors. J Clin Invest. 2009;119:1688–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Shirley JL, Keeler GD, Sherman A, Zolotukhin I, Markusic DM, Hoffman BE, et al. Type I IFN sensing by cDCs and CD4+ T cell help are both requisite for cross-priming of AAV capsid-specific CD8+ T cells. Mol Ther. 2020;28:758–70.

    Article  CAS  PubMed  Google Scholar 

  42. Bočkor L, Bortolussi G, Iaconcig A, Chiaruttini G, Tiribelli C, Giacca M, et al. Repeated AAV-mediated gene transfer by serotype switching enables long-lasting therapeutic levels of hUgt1a1 enzyme in a mouse model of Crigler–Najjar Syndrome Type I. Gene Ther. 2017;24:649–60.

    Article  PubMed  Google Scholar 

  43. Majowicz A, Salas D, Zabaleta N, Rodríguez-Garcia E, González-Aseguinolaza G, Petry H, et al. Successful repeated hepatic gene delivery in mice and non-human primates achieved by sequential administration of AAV5ch and AAV1. Mol Ther. 2017;25:1831–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ge Y, Powell S, Roey MV, McArthur JG. Factors influencing the development of an anti–factor IX (FIX) immune response following administration of adeno-associated virus–FIX. Blood. 2001;97:3733–7.

    Article  CAS  PubMed  Google Scholar 

  45. McIntosh JH, Cochrane M, Cobbold S, Waldmann H, Nathwani SA, Davidoff AM, et al. Successful attenuation of humoral immunity to viral capsid and transgenic protein following AAV-mediated gene transfer with a non-depleting CD4 antibody and cyclosporine. Gene Ther. 2012;19:78–85.

    Article  CAS  PubMed  Google Scholar 

  46. Mingozzi F, Chen Y, Murphy SL, Edmonson SC, Tai A, Price SD, et al. Pharmacological modulation of humoral immunity in a nonhuman primate model of AAV gene transfer for hemophilia B. Mol Ther. 2012;20:1410–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Monteilhet V, Saheb S, Boutin S, Leborgne C, Veron P, Montus M-F, et al. A 10 patient case report on the impact of plasmapheresis upon neutralizing factors against adeno-associated virus (AAV) types 1, 2, 6, and 8. Mol Ther. 2011;19:2084–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Orlowski A, Katz MG, Gubara SM, Fargnoli AS, Fish KM, Weber T. Successful transduction with AAV vectors after selective depletion of anti-AAV antibodies by immunoadsorption. Mol Ther Methods Clin Dev. 2020;16:192–203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Corti M, Elder ME, Falk DJ, Lawson L, Smith BK, Nayak S, et al. B-cell depletion is protective against anti-AAV capsid immune response: a human subject case study. Mol Ther Methods Clin Dev. 2014;1:14033.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Goldszmid Romina S, Dzutsev A, Trinchieri G. Host immune response to infection and cancer: unexpected commonalities. Cell Host Microbe. 2014;15:295–305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Kitamura D, Roes J, Kühn R, Rajewsky K. A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin f.l chain gene. Nature. 1991;350:4.

  52. Lee DSW, Rojas OL, Gommerman JL. B cell depletion therapies in autoimmune disease: advances and mechanistic insights. Nat Rev Drug Discov. 2021;20:179–99.

    Article  CAS  PubMed  Google Scholar 

  53. Envigo. Rag2-Il2rg double knockout mice (R2G2®) B6;129-Rag2tm1FwaII2rgtm1Rsky/DwlHsd. Envigo. 2020. https://www.envigo.com/model/b6-129-rag2tm1fwaii2rgtm1rsky-dwlhsd.

  54. Ho ML, Adler BA, Torre ML, Silberg JJ, Suh J. SCHEMA computational design of virus capsid chimeras: calibrating how genome packaging, protection, and transduction correlate with calculated structural disruption. ACS Synth Biol. 2013;2:724–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Schuster DJ, Dykstra JA, Riedl MS, Kitto KF, Belur LR, McIvor RS, et al. Biodistribution of adeno-associated virus serotype 9 (AAV9) vector after intrathecal and intravenous delivery in mouse. Front Neuroanat. 2014;8:42.

  56. Srivastava A. In vivo tissue-tropism of adeno-associated viral vectors. Curr Opin Virol. 2016;21:75–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Zincarelli C, Soltys S, Rengo G, Rabinowitz JE. Analysis of AAV serotypes 1–9 mediated gene expression and tropism in mice after systemic injection. Mol Ther. 2008;16:1073–80.

    Article  CAS  PubMed  Google Scholar 

  58. Wang L, Calcedo R, Bell P, Lin J, Grant RL, Siegel DL, et al. Impact of pre-existing immunity on gene transfer to nonhuman primate liver with adeno-associated virus 8 vectors. Hum Gene Ther. 2011;22:1389–401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Peters CW, Maguire CA, Hanlon KS. Delivering AAV to the central nervous and sensory systems. Trends Pharmacol Sci. 2021;42:461–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Haggerty DL, Grecco GG, Reeves KC, Atwood B. Adeno-associated viral vectors in neuroscience research. Mol Ther Methods Clin Dev. 2020;17:69–82.

    Article  CAS  PubMed  Google Scholar 

  61. Galvan A, Stauffer WR, Acker L, El-Shamayleh Y, Inoue K-I, Ohayon S, et al. Nonhuman primate optogenetics: recent advances and future directions. J Neurosci. 2017;37:10894.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Chan KY, Jang MJ, Yoo BB, Greenbaum A, Ravi N, Wu W-L, et al. Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems. Nat Neurosci. 2017;20:1172–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Lorain S, Gross D-A, Goyenvalle A, Danos O, Davoust J, Garcia L. Transient immunomodulation allows repeated injections of AAV1 and correction of muscular dystrophy in multiple muscles. Mol Ther. 2008;16:541–7.

    Article  CAS  PubMed  Google Scholar 

  64. Siders WM, Shields J, Kaplan J, Lukason M, Woodworth L, Wadsworth S, et al. Cytotoxic T lymphocyte responses to transgene product, not adeno-associated viral capsid protein, limit transgene expression in mice. Hum Gene Ther. 2009;20:11–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Chirmule N, Xiao W, Truneh A, Schnell MA, Hughes JV, Zoltick P, et al. Humoral immunity to adeno-associated virus type 2 vectors following administration to murine and nonhuman primate muscle. J Virol. 2000;74:2420–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Xiao W, Chirmule N, Schnell MA, Tazelaar J, Hughes JV, Wilson JM. Route of administration determines induction of T-cell-independent humoral responses to adeno-associated virus vectors. Mol Ther. 2000;1:323–9.

    Article  CAS  PubMed  Google Scholar 

  67. Xin K-Q, Mizukami H, Urabe M, Toda Y, Shinoda K, Yoshida A, et al. Induction of robust immune responses against human immunodeficiency virus is supported by the inherent tropism of adeno-associated virus type 5 for dendritic cells. J Virol. 2006;80:11899–910.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Martino AT, Suzuki M, Markusic DM, Zolotukhin I, Ryals RC, Moghimi B, et al. The genome of self-complementary adeno-associated viral vectors increases Toll-like receptor 9–dependent innate immune responses in the liver. Blood. 2011;117:6459–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Moghadam F, LeGraw R, Velazquez JJ, Yeo NC, Xu C, Park J, et al. Synthetic immunomodulation with a CRISPR super-repressor in vivo. Nat Cell Biol. 2020;22:1143–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Penaranda C, Tang Q, Bluestone JA. Anti-CD3 therapy promotes tolerance by selectively depleting pathogenic cells while preserving regulatory T cells. J Immunol. 2011;187:2015–22.

    Article  CAS  PubMed  Google Scholar 

  71. Leborgne C, Barbon E, Alexander JM, Hanby H, Delignat S, Cohen DM, et al. IgG-cleaving endopeptidase enables in vivo gene therapy in the presence of anti-AAV neutralizing antibodies. Nat Med. 2020;26:1096–101.

  72. Thévenot E, Jordão JF, O'Reilly MA, Markham K, Weng Y-Q, Foust KD, et al. Targeted delivery of self-complementary adeno-associated virus serotype 9 to the brain, using magnetic resonance imaging-guided focused ultrasound. Hum Gene Ther. 2012;23:1144–55.

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Acknowledgements

The authors acknowledge the use of equipment at the Shared Equipment Authority of Rice University and a Rice University Academy Fellowship to MIJ. The authors would also like to acknowledge the support of the Single Cell Genomics Core at Baylor College of Medicine, partially supported by NIH shared instrument grants (S10OD023469, S10OD025240) and P30EY002520.

Funding

This work was supported by the National Institutes of Health under grant numbers grant numbers R01CA272769 (HCH), R01CA207497 (JS), F30HL146032 (MC), F31AI161906-01A1 (CC), and the Cancer Prevention Research Institute of Texas grant number RR160047 (OV).

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  1. These authors contributed equally: Maria Chen, Boram Kim, Maria I. Jarvis.

Authors and Affiliations

  1. Department of Bioengineering, Rice University, Houston, TX, USA

    Maria Chen, Boram Kim, Maria I. Jarvis, Samantha Fleury, Shuyun Deng, Shirin Nouraein, Susan Butler, Sangsin Lee, H. Courtney Hodges, Jerzy O. Szablowski, Junghae Suh & Omid Veiseh

  2. Medical Scientist Training Program, Baylor College of Medicine, Houston, TX, USA

    Maria Chen

  3. Rice Neuroengineering Initiative, George R. Brown School of Engineering, Rice University, Houston, TX, USA

    Shirin Nouraein, Sangsin Lee & Jerzy O. Szablowski

  4. Translational Biology and Molecular Medicine Graduate Program, Baylor College of Medicine, Houston, TX, USA

    Courtney Chambers

  5. Center for Precision Environmental Health, Department of Molecular and Cellular Biology, and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA

    H. Courtney Hodges

  6. Systems, Synthetic, and Physical Biology Program, Rice University, Houston, TX, USA

    Jerzy O. Szablowski & Junghae Suh

  7. Department of BioSciences, Rice University, Houston, TX, USA

    Junghae Suh

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Contributions

Conceptualization: MC, BK, MIJ, JS, OV. Methodology: MC, BK, MIJ, SF, SD, SN, SB, SL, CC, HCH, JOS, JS, OV. Investigation: MC, BK, MIJ, SF, SD, SN, SB, SL, CC. Visualization: MC, BK, MIJ, SF, SN, SL, CC. Supervision: HCH, JOS, JS, OV. Writing: MC, BK, MIJ, SF, SN, SL, CC, HCH, JOS, JS, OV.

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Correspondence to Junghae Suh or Omid Veiseh.

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JS is an employee of Biogen Inc. as of 2019. OV is a member of the Scientific Advisory Board of Sigilon Therapeutics and holds equity in the Avenge Bio and Pana Bio. The remaining authors declare no competing interests.

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Chen, M., Kim, B., Jarvis, M.I. et al. Immune profiling of adeno-associated virus response identifies B cell-specific targets that enable vector re-administration in mice. Gene Ther 30, 429–442 (2023). https://doi.org/10.1038/s41434-022-00371-0

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