In Silico Reconstruction of the Viral Evolutionary Lineage Yields a Potent Gene Therapy Vector
Open accessAbstract
Adeno-associated virus (AAV) vectors have emerged as a gene-delivery platform with demonstrated safety and efficacy in a handful of clinical trials for monogenic disorders. However, limitations of the current generation vectors often prevent broader application of AAV gene therapy. Efforts to engineer AAV vectors have been hampered by a limited understanding of the structure-function relationship of the complex multimeric icosahedral architecture of the particle. To develop additional reagents pertinent to further our insight into AAVs, we inferred evolutionary intermediates of the viral capsid using ancestral sequence reconstruction. In-silico-derived sequences were synthesized de novo and characterized for biological properties relevant to clinical applications. This effort led to the generation of nine functional putative ancestral AAVs and the identification of Anc80, the predicted ancestor of the widely studied AAV serotypes 1, 2, 8, and 9, as a highly potent in vivo gene therapy vector for targeting liver, muscle, and retina.
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In silico design approach to reconstruct and discover new capsid was first reported in 2015.
“With technological advancements of computational modeling and machine learning, an in silico design approach to reconstruct and discover new capsid was first reported in 2015 [69, 70].”
From Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside (2024) · cites this paper as [69]
The Discussion (page unavailable) says the authors inferred ancestral AAV capsid sequences through in silico modeling and identified a new AAV-like particle, Anc80L65. It does not establish that this approach was first reported in 2015; it describes an earlier viral-ancestor reconstruction as a methodological precedent. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAAV8 and Anc80L65 both transduce retinal cells with high efficiencies.
“Effect of serotype on vector reconstitution was studied by comparing AAV8 and Anc80L65, both of which transduce retinal cells with high efficiencies (Zinn et al., 2015).”
From Evaluating Efficiencies of Dual AAV Approaches for Retinal Targeting (2017) · cites this paper as Zinn et al., 2015
The Anc80 serotype, produced by mining the parvovirus ancestral genome, has promise as a safer vector for gene therapy.
“This strategy produced the Anc80 serotype with the promise of a safer vector for GT [116].”
From Risk mitigation of immunogenicity: a key to personalized retinal gene therapy (2021) · cites this paper as [116]
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UCSF Chimera—A visualization system for exploratory research and analysis
Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004) · Journal of Computational Chemistry · doi:10.1002/jcc.20084 · Cited by 45,260 · see citing works
Guindon, S., Dufayard, J.-F., Lefort, V., Anisimova, M., Hordijk, W., & Gascuel, O. (2010) · Systematic Biology · doi:10.1093/sysbio/syq010 · Cited by 18,376 · see citing works
PAML 4: Phylogenetic Analysis by Maximum Likelihood
Yang, Z. (2007) · Molecular Biology and Evolution · doi:10.1093/molbev/msm088 · Cited by 13,879 · see citing works
T-Coffee: A novel method for fast and accurate multiple sequence alignment.
Notredame, C., Higgins, D., & Heringa, J. (2000) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.4042 · Cited by 7,321 · see citing works
Approximate likelihood-ratio test for branches: A fast, accurate, and powerful alternative
Anisimova, M., & Gascuel, O. (2006) · Systematic Biology · doi:10.1080/10635150600755453 · Cited by 2,693 · see citing works
ProtTest 3: fast selection of best-fit models of protein evolution
Darriba, D., Taboada, G. L., Doallo, R., & Posada, D. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr088 · Cited by 2,677 · see citing works
Safety and Efficacy of Gene Transfer for Leber's Congenital Amaurosis
Maguire, A. M., Simonelli, F., Pierce, E. A., Pugh, E. N., Mingozzi, F., Bennicelli, J., Banfi, S., Marshall, K. A., Testa, F., Surace, E. M., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802315 · Cited by 2,145 · see citing works
Effect of gene therapy on visual function in Leber’s congenital amaurosis
Bainbridge, J. W. B., Smith, A. J., Barker, S. S., Robbie, S., Henderson, R., Balaggan, K., Viswanathan, A., Holder, G. E., Stockman, A., Tyler, N., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802268 · Cited by 1,924 · see citing works
Adenovirus-Associated Virus Vector–Mediated Gene Transfer in Hemophilia B
Nathwani, A. C., Tuddenham, E. G. D., Rangarajan, S., Rosales, C., McIntosh, J., Linch, D. C., Chowdary, P., Riddell, A., Pie, A. J., Harrington, C., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1108046 · Cited by 1,864 · see citing works
Clades of Adeno-Associated Viruses Are Widely Disseminated in Human Tissues
Gao, G., Vandenberghe, L. H., Alvira, M. R., Lu, Y., Calcedo, R., Zhou, X., & Wilson, J. M. (2004) · Journal of Virology · doi:10.1128/jvi.78.12.6381-6388.2004 · Cited by 1,070 · see citing works
Self-citationAn algorithm for progressive multiple alignment of sequences with insertions
Löytynoja, A., & Goldman, N. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409137102 · Cited by 885 · see citing works
ProtTest-HPC: Fast Selection of Best-Fit Models of Protein Evolution
Darriba, D., Taboada, G. L., Doallo, R., & Posada, D. (2011) · Lecture notes in computer science · doi:10.1007/978-3-642-21878-1_22 · Cited by 811 · see citing works
Worldwide epidemiology of neutralizing antibodies to adeno-associated viruses
Calcedo, R., Vandenberghe, L. H., Gao, G., Lin, J., & Wilson, J. M. (2009) · The Journal of Infectious Diseases · doi:10.1086/595830 · Cited by 808 · see citing works
Self-citationPhylogeny-Aware Gap Placement Prevents Errors in Sequence Alignment and Evolutionary Analysis
Löytynoja, A., & Goldman, N. (2008) · Science · doi:10.1126/science.1158395 · Cited by 803 · see citing works
MacLaren, R. E., Groppe, M., Barnard, A. R., Cottriall, C. L., Tolmachova, T., Seymour, L., Clark, K. R., During, M. J., Cremers, F. P. M., Black, G. C. M., et al. (2014) · The Lancet · doi:10.1016/s0140-6736(13)62117-0 · Cited by 796 · see citing works
Cd8(+) T-Cell Responses to Adeno-Associated Virus Capsid in Humans
Mingozzi, F., Maus, M. V., Hui, D. J., Sabatino, D. E., Murphy, S. L., Rasko, J. E. J., Ragni, M. V., Manno, C. S., Sommer, J., Jiang, H., et al. (2007) · Nature Medicine · doi:10.1038/nm1549 · Cited by 748 · see citing works
Dalkara, D., Byrne, L. C., Klimczak, R. R., Visel, M., Yin, L., Merigan, W. H., Flannery, J. G., & Schaffer, D. V. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005708 · Cited by 734 · cited 2× · see citing works
“Forward genetic studies have resulted in important findings (Adachi et al., 2014; Asuri et al., 2012; Bartel et al., 2012; Dalkara et al., 2013; Huttner et al., 2003; Koerber et al., 2008; Li et al., 2008; Lisowski et al., 2014; Maheshri et al., 2006; Mays et al., 2013; Perabo et al., 2003; Shen et al., 2007; Wu et al…”
BackgroundJacobson, S. G. (2012) · Archives of Ophthalmology · doi:10.1001/archophthalmol.2011.298 · Cited by 639 · see citing works
The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy
Xie, Q., Bu, W., Bhatia, S., Hare, J., Somasundaram, T., Azzi, A., & Chapman, M. S. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.162250899 · Cited by 612 · see citing works
Directed evolution of adeno-associated virus yields enhanced gene delivery vectors
Maheshri, N., Koerber, J. T., Kaspar, B. K., & Schaffer, D. V. (2006) · Nature Biotechnology · doi:10.1038/nbt1182 · Cited by 538 · cited 2× · see citing works
“Forward genetic studies have resulted in important findings (Adachi et al., 2014; Asuri et al., 2012; Bartel et al., 2012; Dalkara et al., 2013; Huttner et al., 2003; Koerber et al., 2008; Li et al., 2008; Lisowski et al., 2014; Maheshri et al., 2006; Mays et al., 2013; Perabo et al., 2003; Shen et al., 2007; Wu et al…”
BackgroundNew recombinant serotypes of AAV vectors
Gao, G., Vandenberghe, L., & Wilson, J. (2005) · Current Gene Therapy · doi:10.2174/1566523054065057 · Cited by 487 · see citing works
Self-citationSelection and evaluation of clinically relevant AAV variants in a xenograft liver model
Lisowski, L., Dane, A. P., Chu, K., Zhang, Y., Cunningham, S. C., Wilson, E. M., Nygaard, S., Grompe, M., Alexander, I. E., & Kay, M. A. (2014) · Nature · doi:10.1038/nature12875 · Cited by 450 · cited 2× · see citing works
“Forward genetic studies have resulted in important findings (Adachi et al., 2014; Asuri et al., 2012; Bartel et al., 2012; Dalkara et al., 2013; Huttner et al., 2003; Koerber et al., 2008; Li et al., 2008; Lisowski et al., 2014; Maheshri et al., 2006; Mays et al., 2013; Perabo et al., 2003; Shen et al., 2007; Wu et al…”
BackgroundAuricchio, A. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.26.3075 · Cited by 394 · see citing works
Wu, P., Xiao, W. S., Conlon, T. J., Hughes, J. A., Agbandje‐McKenna, M., Ferkol, T. W., Flotte, T. R., & Muzyczka, N. (2000) · Journal of Virology · doi:10.1128/jvi.74.18.8635-8647.2000 · Cited by 390 · see citing works
Identification of a heparin-binding motif on adeno-associated virus type 2 capsids
Kern, A., Schmidt, K., Leder, C., Müller, O. J., Wobus, C. E., Bettinger, K., Von der Lieth, C. W., King, J. A., & Kleinschmidt, J. A. (2003) · Journal of Virology · doi:10.1128/jvi.77.20.11072-11081.2003 · Cited by 380 · see citing works
Pre-existing Anti–Adeno-Associated Virus Antibodies as a Challenge in AAV Gene Therapy
Louis Jeune, V., Joergensen, J. A., Hajjar, R. J., & Weber, T. (2013) · Human Gene Therapy Methods · doi:10.1089/hgtb.2012.243 · Cited by 358 · see citing works
Girod, A., Wobus, C. E., Zádori, Z., Ried, M., Leike, K., Tijssen, P., Kleinschmidt, J. A., & Hallek, M. (2002) · Journal of General Virology · doi:10.1099/0022-1317-83-5-973 · Cited by 354 · see citing works
Rapid, Simple, and Versatile Manufacturing of Recombinant Adeno-Associated Viral Vectors at Scale
Lock, M. W., Alvira, M. R., Vandenberghe, L. H., Samanta, A., Toelen, J., Debyser, Z., & Wilson, J. M. (2010) · Human Gene Therapy · doi:10.1089/hum.2010.055 · Cited by 328 · see citing works
Self-citationBrantly, M. L., Chulay, J. D., Wang, L., Mueller, C., Humphries, M., Spencer, L. T., Rouhani, F., Conlon, T. J., Calcedo, R., Betts, M. R., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904514106 · Cited by 327 · see citing works
Adeno-associated viruses undergo substantial evolution in primates during natural infections
Gao, G., Alvira, M. R., Somanathan, S., Lü, Y., Vandenberghe, L. H., Rux, J. J., Calcedo, R., Sanmiguel, J. C., Abbas, Z., & Wilson, J. M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0937739100 · Cited by 323 · see citing works
Self-citationUnrestricted Hepatocyte Transduction with Adeno-Associated Virus Serotype 8 Vectors in Mice
Nakai, H., Fuess, S., Storm, T. A., Muramatsu, S., Nara, Y., & Kay, M. A. (2004) · Journal of Virology · doi:10.1128/jvi.79.1.214-224.2005 · Cited by 322 · see citing works
Hastie, E. L., & Samulski, R. J. (2015) · Human Gene Therapy · doi:10.1089/hum.2015.025 · Cited by 284 · see citing works
Li, W., Asokan, A., Wu, Z., Van Dyke, T., DiPrimio, N., Johnson, J. S., Govindaswamy, L., Agbandje-McKenna, M., Leichtle, S., Eugene Redmond Jr, D., et al. (2008) · Molecular Therapy · doi:10.1038/mt.2008.100 · Cited by 261 · see citing works
Novel adeno-associated virus serotypes efficiently transduce murine photoreceptors
Allocca, M., Mussolino, C., Garcia-Hoyos, M., Sanges, D., Iodice, C., Petrillo, M., Vandenberghe, L. H., Wilson, J. M., Marigo, V., Surace, E. M., et al. (2007) · Journal of Virology · doi:10.1128/jvi.01327-07 · Cited by 246 · see citing works
Self-citationIn vitro selection of viral vectors with modified tropism: the adeno-associated virus display
Perabò, L., Büning, H., Kofler, D. M., Ried, M. U., Girod, A., Wendtner, C., Enssle, J., & Hallek, M. J. (2003) · Molecular Therapy · doi:10.1016/s1525-0016(03)00123-0 · Cited by 232 · see citing works
Structural insight into the unique properties of adeno-associated virus serotype 9
DiMattia, M. A., Nam, H.-J., Van Vliet, K., Mitchell, M., Bennett, A., Gurda, B. L., McKenna, R., Olson, N. H., Sinkovits, R. S., Potter, M., et al. (2012) · Journal of Virology · doi:10.1128/jvi.07232-11 · Cited by 219 · see citing works
Evolution of increased complexity in a molecular machine
Finnigan, G. C., Hanson-Smith, V., Stevens, T. H., & Thornton, J. W. (2012) · Nature · doi:10.1038/nature10724 · Cited by 212 · see citing works
Heparin binding directs activation of T cells against adeno-associated virus serotype 2 capsid
Vandenberghe, L. H., Wang, L., Somanathan, S., Zhi, Y., Figueredo, J., Calcedo, R., Sanmiguel, J., Desai, R. A., Chen, C. S., Johnston, J., et al. (2006) · Nature Medicine · doi:10.1038/nm1445 · Cited by 208 · see citing works
Self-citationLochrie, M. A., Tatsuno, G. P., Christie, B., McDonnell, J. W., Zhou, S., Surosky, R., Pierce, G. F., & Colosi, P. (2006) · Journal of Virology · doi:10.1128/jvi.80.2.821-834.2006 · Cited by 201 · see citing works
Lessons learned from the clinical development and market authorization of Glybera
Bryant, L. M., Christopher, D. M., Giles, A. R., Hinderer, C., Rodriguez, J. L., Smith, J. B., Traxler, E. A., Tycko, J., Wojno, A. P., & Wilson, J. M. (2013) · Human Gene Therapy Clinical Development · doi:10.1089/humc.2013.087 · Cited by 189 · see citing works
DNA Shuffling of Adeno-associated Virus Yields Functionally Diverse Viral Progeny
Koerber, J. T., Jang, J.-H., & Schaffer, D. V. (2008) · Molecular Therapy · doi:10.1038/mt.2008.167 · Cited by 181 · see citing works
Grieger, J. C., Snowdy, S., & Samulski, R. J. (2006) · Journal of Virology · doi:10.1128/jvi.02723-05 · Cited by 172 · cited 2× · see citing works
“, 2000), phospholipase activity and nuclear localization activity on VP1,2 unique domains (Girod et al., 2002; Grieger et al., 2006), a limited number of docking sites for monoclonal antibodies (DiMattia et al.”
BackgroundDirected evolution of novel adeno-associated viruses for therapeutic gene delivery
Bartel, M. A., Weinstein, J. R., & Schaffer, D. V. (2012) · Gene Therapy · doi:10.1038/gt.2012.20 · Cited by 162 · see citing works
Adachi, K., Enoki, T., Kawano, Y., Veraz, M., & Nakai, H. (2014) · Nature Communications · doi:10.1038/ncomms4075 · Cited by 149 · see citing works
Identification of the Galactose Binding Domain of the Adeno-Associated Virus Serotype 9 Capsid
Bell, C. L., Gurda, B. L., Vliet, K. V., Agbandje‐McKenna, M., & Wilson, J. M. (2012) · Journal of Virology · doi:10.1128/jvi.00448-12 · Cited by 138 · see citing works
The Pleiotropic Effects of Natural AAV Infections on Liver-directed Gene Transfer in Macaques
Wang, L., Calcedo, R., Wang, H., Bell, P., Grant, R., Vandenberghe, L. H., Sanmiguel, J., Morizono, H., Batshaw, M. L., & Wilson, J. M. (2010) · Molecular Therapy · doi:10.1038/mt.2009.245 · Cited by 130 · see citing works
Self-citationCapsid antibodies to different adeno-associated virus serotypes bind common regions
Gurda, B. L., DiMattia, M. A., Miller, E. B., Bennett, A., McKenna, R., Weichert, W. S., Nelson, C. D., Chen, W.-J., Muzyczka, N., Olson, N. H., et al. (2013) · Journal of Virology · doi:10.1128/jvi.00622-13 · Cited by 127 · see citing works
Huttner, N. A., Girod, A., Perabo, L., Edbauer, D., Kleinschmidt, J. A., Büning, H., & Hallek, M. (2003) · Gene Therapy · doi:10.1038/sj.gt.3302123 · Cited by 124 · see citing works
Asuri, P., Bartel, M. A., Vazin, T., Jang, J.-H., Wong, T. B., & Schaffer, D. V. (2012) · Molecular Therapy · doi:10.1038/mt.2011.255 · Cited by 119 · see citing works
Nakai, H., Thomas, C. E., Storm, T. A., Fuess, S., Powell, S. K., Wright, J. F., & Kay, M. A. (2002) · Journal of Virology · doi:10.1128/jvi.76.22.11343-11349.2002 · Cited by 99 · see citing works
Mapping a Neutralizing Epitope onto the Capsid of Adeno-Associated Virus Serotype 8
Gurda, B. L., Raupp, C., Popa-Wagner, R., Naumer, M., Olson, N. H., Ng, R., McKENNA, R. V., Baker, T. S., Kleinschmidt, J. A., & Agbandje‐McKenna, M. (2012) · Journal of Virology · doi:10.1128/jvi.00218-12 · Cited by 93 · see citing works
Vandenberghe, L. H., Breous, E., Nam, H.-J., Gao, G., Xiao, R., Sandhu, A., Johnston, J., Debyser, Z., Agbandje‐McKenna, M., & Wilson, J. M. (2009) · Gene Therapy · doi:10.1038/gt.2009.101 · Cited by 72 · see citing works
Self-citationCharacterization of the Relationship of AAV Capsid Domain Swapping to Liver Transduction Efficiency
Shen, X., Storm, T., & Kay, M. A. (2007) · Molecular Therapy · doi:10.1038/sj.mt.6300293 · Cited by 59 · see citing works
Characterization of a Putative Ancestor of Coxsackievirus B5
Gullberg, M., Tolf, C., Jonsson, N., Mulders, M. N., Savolainen‐Kopra, C., Hovi, T., Ranst, M. A. V., Lemey, P., Hafenstein, S. L., & Lindberg, A. M. (2010) · Journal of Virology · doi:10.1128/jvi.00071-10 · Cited by 38 · see citing works
Adeno-associated virus delivery of broadly neutralizing antibodies
Schnepp, B. C., & Johnson, P. R. (2014) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0000000000000056 · Cited by 33 · see citing works
Mays, L. E., Wang, L., Tenney, R. M., Bell, P. L., Nam, H.-J., Lin, J., Gurda, B. L., Vliet, K. V., Mikals, K., Agbandje‐McKenna, M., et al. (2013) · Journal of Virology · doi:10.1128/jvi.00596-13 · Cited by 27 · see citing works
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Wang, D., Tai, P. W. L., & Gao, G. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0012-9 · Cited by 2,444 · see citing works
Viral vector platforms within the gene therapy landscape
Bulcha, J. T., Wang, Y., Ma, H., Tai, P. W. L., & Gao, G. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00487-6 · Cited by 1,404 · see citing works
Engineering adeno-associated virus vectors for gene therapy
Li, C., & Samulski, R. J. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-019-0205-4 · Cited by 1,175 · see citing works
In vivo gene editing in dystrophic mouse muscle and muscle stem cells
Tabebordbar, M., Zhu, K., Cheng, J. K. W., Chew, W. L., Widrick, J. J., Yan, W. X., Maesner, C., Wu, E. Y., Xiao, R., Ran, F. A., et al. (2016) · Science · doi:10.1126/science.aad5177 · Cited by 1,046 · see citing works
Self-citationEmerging issues in AAV-mediated in vivo gene therapy
Colella, P., Ronzitti, G., & Mingozzi, F. (2018) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2017.11.007 · Cited by 881 · see citing works
A synthetic AAV vector enables safe and efficient gene transfer to the mammalian inner ear
Landegger, L. D., Pan, B., Askew, C., Wassmer, S. J., Gluck, S. D., Galvin, A., Taylor, R., Forge, A., Stankovic, K. M., Holt, J. R., et al. (2017) · Nature Biotechnology · doi:10.1038/nbt.3781 · Cited by 325 · see citing works
Self-citationKeeler, A. M., & Flotte, T. R. (2019) · Annual Review of Virology · doi:10.1146/annurev-virology-092818-015530 · Cited by 322 · see citing works
AAV <i>cis</i> -regulatory sequences are correlated with ocular toxicity
Xiong, W., Wu, D. M., Xue, Y., Wang, S. K., Chung, M. J., Ji, X., Rana, P., Zhao, S. R., Mai, S., & Cepko, C. L. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1821000116 · Cited by 249 · see citing works
Weinmann, J., Weis, S., Sippel, J., Tulalamba, W., Remes, A., El Andari, J., Herrmann, A.-K., Pham, Q. H., Borowski, C., Hille, S., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19230-w · Cited by 259 · see citing works
Retinal stimulation strategies to restore vision: fundamentals and systems
Yue, L., Weiland, J. D., Roska, B., & Humayun, M. S. (2016) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2016.05.002 · Cited by 272 · see citing works
Unraveling the complex story of immune responses to AAV vectors trial after trial.
Vandamme, C., Adjali, O., & Mingozzi, F. (2017) · Human Gene Therapy · doi:10.1089/hum.2017.150 · Cited by 234 · see citing works
Tse, L. V., Klinc, K. A., Madigan, V. J., Castellanos Rivera, R. M., Wells, L. F., Havlik, L. P., Smith, J. K., Agbandje-McKenna, M., & Asokan, A. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1704766114 · Cited by 210 · see citing works
Next-generation AAV vectors—Do not judge a virus (only) by its cover
Domenger, C., & Grimm, D. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz148 · Cited by 147 · see citing works
Novel AAV capsids for intravitreal gene therapy of photoreceptor disorders
Pavlou, M., Schön, C., Occelli, L. M., Rossi, A., Meumann, N., Boyd, R. F., Bartoe, J. T., Siedlecki, J., Gerhardt, M. J., Babutzka, S., et al. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.202013392 · Cited by 135 · see citing works
Davidsson, M., Wang, G., Aldrin-Kirk, P., Cardoso, T., Nolbrant, S., Hartnor, M., Mudannayake, J., Parmar, M., & Björklund, T. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1910061116 · Cited by 142 · see citing works
Tordo, J., O’Leary, C., Antunes, A. S. L. M., Palomar, N., Aldrin-Kirk, P., Basche, M., Bennett, A., D’Souza, Z., Gleitz, H., Godwin, A., et al. (2018) · Brain · doi:10.1093/brain/awy126 · Cited by 113 · see citing works
Chemical modification of the adeno-associated virus capsid to improve gene delivery
Mével, M., Bouzelha, M., Leray, A., Pacouret, S., Guilbaud, M., Penaud-Budloo, M., Alvarez-Dorta, D., Dubreil, L., Gouin, S. G., Combal, J. P., et al. (2020) · Chemical Science · doi:10.1039/c9sc04189c · Cited by 92 · see citing works
Self-citationEvaluating Efficiencies of Dual AAV Approaches for Retinal Targeting
Carvalho, L. S., Turunen, H. T., Wassmer, S. J., Luna-Velez, M. V., Xiao, R., Bennett, J., & Vandenberghe, L. H. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00503 · Cited by 86 · see citing works
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Hudry, E., Andres-Mateos, E., Lerner, E. P., Volak, A., Cohen, O., Hyman, B. T., Maguire, C. A., & Vandenberghe, L. H. (2018) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2018.07.006 · Cited by 84 · see citing works
Self-citationVidović, D., Carlon, M. S., da Cunha, M. F., Dekkers, J. F., Hollenhorst, M. I., Bijvelds, M. J. C., Ramalho, A. S., Van den Haute, C., Ferrante, M., Baekelandt, V., et al. (2016) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201505-0914oc · Cited by 74 · see citing works
Adeno-Associated Viral Vectors as a Tool for Large Gene Delivery to the Retina
Trapani, I. (2019) · Genes · doi:10.3390/genes10040287 · Cited by 73 · see citing works
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Pacouret, S., Bouzelha, M., Shelke, R., Andres-Mateos, E., Xiao, R., Maurer, A., Mevel, M., Turunen, H., Barungi, T., Penaud-Budloo, M., et al. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.04.001 · Cited by 69 · see citing works
Self-citationHsu, H.-L., Brown, A., Loveland, A. B., Lotun, A., Xu, M., Luo, L., Xu, G., Li, J., Ren, L., Su, Q., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17047-1 · Cited by 63 · see citing works
Carvalho, L. S., Xiao, R., Wassmer, S. J., Langsdorf, A., Zinn, E., Pacouret, S., Shah, S., Comander, J. I., Kim, L. A., Lim, L., et al. (2018) · Human Gene Therapy · doi:10.1089/hum.2017.154 · Cited by 63 · see citing works
Self-citationAAV capsid design: A Goldilocks challenge
Zolotukhin, S., & Vandenberghe, L. H. (2022) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2022.01.003 · Cited by 64 · see citing works
Self-citationOligonucleotide conjugated multi-functional adeno-associated viruses
Katrekar, D., Moreno, A. M., Chen, G., Worlikar, A., & Mali, P. (2018) · Scientific Reports · doi:10.1038/s41598-018-21742-x · Cited by 57 · see citing works
Ilyinskii, P. O., Michaud, A. M., Roy, C. J., Rizzo, G. L., Elkins, S. L., Capela, T., Chowdhury, A. C., Leung, S. S., & Kishimoto, T. K. (2021) · Science Advances · doi:10.1126/sciadv.abd0321 · Cited by 56 · see citing works
Humoral immune responses to <scp>AAV</scp> gene therapy in the ocular compartment
Whitehead, M., Osborne, A., Yu‐Wai‐Man, P., & Martin, K. (2021) · Biological Reviews · doi:10.1111/brv.12718 · Cited by 52 · see citing works
Welles, H. C., Jennewein, M. F., Mason, R. D., Narpala, S., Wang, L., Cheng, C., Zhang, Y., Todd, J.-P., Lifson, J. D., Balazs, A. B., et al. (2018) · PLOS Pathogens · doi:10.1371/journal.ppat.1007395 · Cited by 53 · see citing works
Optimization of AAV vectors to target persistent viral reservoirs
Colón-Thillet, R., Jerome, K. R., & Stone, D. (2021) · Virology Journal · doi:10.1186/s12985-021-01555-7 · Cited by 50 · see citing works
Xu, L., Yao, S., Ding, Y. E., Xie, M., Feng, D., Sha, P., Tan, L., Bei, F., & Yao, Y. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05661-2 · Cited by 48 · see citing works
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Ail, D., Malki, H., Zin, E. A., & Dalkara, D. (2023) · The Application of Clinical Genetics · doi:10.2147/tacg.s383453 · Cited by 40 · see citing works
In Situ Detection of Adeno-associated Viral Vector Genomes with SABER-FISH
Wang, S. K., Lapan, S. W., Hong, C. M., Krause, T. B., & Cepko, C. L. (2020) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2020.10.003 · Cited by 36 · see citing works
Ilyinskii, P. O., Michaud, A. M., Rizzo, G. L., Roy, C. J., Leung, S. S., Elkins, S. L., Capela, T., Chowdhury, A., Li, L., Chandler, R. J., et al. (2021) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2021.06.015 · Cited by 39 · see citing works
Self-citationAn adeno-associated virus variant enabling efficient ocular-directed gene delivery across species
Luo, S., Jiang, H., Li, Q., Qin, Y., Yang, S., Li, J., Xu, L., Gou, Y., Zhang, Y., Liu, F., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48221-4 · Cited by 39 · see citing works
Evasion of Pre-Existing Immunity to Cas9: A Prerequisite for Successful Genome Editing In Vivo?
Wignakumar, T., & Fairchild, P. J. (2019) · Current Transplantation Reports · doi:10.1007/s40472-019-00237-2 · Cited by 19 · see citing works
Risk mitigation of immunogenicity: a key to personalized retinal gene therapy
Varin, J., Morival, C., Maillard, N., Adjali, O., & Cronin, T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222312818 · Cited by 19 · see citing works
Brydon, E. M., Bronstein, R., Buskin, A., Lako, M., Pierce, E. A., & Fernandez-Godino, R. (2019) · doi:10.1101/729160 · Cited by 56 · see citing works
- Authors
- Zinn, E., Pacouret, S., Khaychuk, V., Turunen, H. T., Carvalho, L. S., Andres-Mateos, E., Shah, S., Shelke, R., Maurer, A. C., Plovie, E., Xiao, R., & Vandenberghe, L. H.
- Affiliations
- Massachusetts Eye and Ear Infirmary (US)
- Corresponding author
- Vandenberghe, Luk H.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-08
- Volume
- 12
- Issue
- 6
- Pages
- 1056-1068
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC4536165
- OpenAlex
- W1518729035
- Cited by
- 310
- References
- 56
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 33 · 2023: 18 · 2022: 28 · 2021: 39 · 2020: 40 · 2019: 40 · 2018: 35 · 2017: 33 · 2016: 10 · 2015: 5
- FWCI
- 19.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- TECNALIA Publications (Fundación TECNALIA Research & Innovation) (submittedVersion, public-domain)
- Funders
- National Institutes of Health (1dp1od008267-01)
- National Eye Institute (DP1EY023177)
- National Center for Chronic Disease Prevention and Health Promotion (5DP1EY023177-03)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Environmental Science › Ecology › Bacteriophages and microbial interactions
- Keywords
- adeno-associated virus, ancestral sequence reconstruction, AAV serotypes, liver targeting, monogenic disorders
- MeSH terms
- Dependovirus, Genetic Vectors, Molecular Sequence Data, Genetic Therapy, Gene Transfer Techniques
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