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Selection and evaluation of clinically relevant AAV variants in a xenograft liver model
Open accessAbstract
Recombinant adeno-associated viral (rAAV) vectors have shown early promise in clinical trials. The therapeutic transgene cassette can be packaged in different AAV capsid pseudotypes, each having a unique transduction profile. At present, rAAV capsid serotype selection for a specific clinical trial is based on effectiveness in animal models. However, preclinical animal studies are not always predictive of human outcome. Here, in an attempt to further our understanding of these discrepancies, we used a chimaeric human-murine liver model to compare directly the relative efficiency of rAAV transduction in human versus mouse hepatocytes in vivo. As predicted from preclinical and clinical studies, rAAV2 vectors functionally transduced mouse and human hepatocytes at equivalent but relatively low levels. However, rAAV8 vectors, which are very effective in many animal models, transduced human hepatocytes rather poorly-approximately 20 times less efficiently than mouse hepatocytes. In light of the limitations of the rAAV vectors currently used in clinical studies, we used the same murine chimaeric liver model to perform serial selection using a human-specific replication-competent viral library composed of DNA-shuffled AAV capsids. One chimaeric capsid composed of five different parental AAV capsids was found to transduce human primary hepatocytes at high efficiency in vitro and in vivo, and provided species-selected transduction in primary liver, cultured cells and a hepatocellular carcinoma xenograft model. This vector is an ideal clinical candidate and a reagent for gene modification of human xenotransplants in mouse models of human diseases. More importantly, our results suggest that humanized murine models may represent a more precise approach for both selecting and evaluating clinically relevant rAAV serotypes for gene therapeutic applications.
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“AAV-NP59 also elicited reduced anti-AAV IgG than AAV-LK03 (119) and AAV8, but not as good as previously discovered engineer capsid AAV-DJ.”
From A versatile toolkit for overcoming AAV immunity (2022) · cites this paper as [119]
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Cites
Organoid Models and Applications in Biomedical Research
Xinaris, C., Brizi, V., & Remuzzi, G. (2015) · The Nephron journals/Nephron journals · doi:10.1159/000433566 · Cited by 3,519
Manno, C. S., Pierce, G. F., Arruda, V. R., Glader, B., Ragni, M., Rasko, J. J. E., Ozelo, M. C., Hoots, K., Blatt, P., Konkle, B., et al. (2006) · Nature Medicine · doi:10.1038/nm1358 · Cited by 2,163
Self-citationEffect 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
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
Self-citationKay, M. A., Manno, C. S., Ragni, M. V., Larson, P. J., Couto, L. B., McClelland, A., Glader, B. E., Chew, A. K., Tai, S. J., Herzog, R. W., et al. (2000) · Nature Genetics · doi:10.1038/73464 · Cited by 1,019
Self-citationBoutin, S., Monteilhet, V., Veron, P., Leborgne, C., Benveniste, O., Montus, M. F., & Masurier, C. (2010) · Human Gene Therapy · doi:10.1089/hum.2009.182 · Cited by 970
Robust expansion of human hepatocytes in Fah−/−/Rag2−/−/Il2rg−/− mice
Azuma, H., Paulk, N., Ranade, A., Dorrell, C., Al-Dhalimy, M., Ellis, E., Strom, S., Kay, M. A., Finegold, M., & Grompe, M. (2007) · Nature Biotechnology · doi:10.1038/nbt1326 · Cited by 835
Self-citationWorldwide 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
Grimm, D., Lee, J. S., Wang, L., Desai, T., Akache, B., Storm, T. A., & Kay, M. A. (2008) · Journal of Virology · doi:10.1128/jvi.00254-08 · Cited by 696
Self-citationDirected 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
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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
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
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Naldini, L. (2015) · Nature · doi:10.1038/nature15818 · Cited by 1,184
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
Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain
Deverman, B. E., Pravdo, P. L., Simpson, B. P., Kumar, S. R., Chan, K. Y., Banerjee, A., Wu, W.-L., Yang, B., Huber, N., Pasca, S. P., et al. (2016) · Nature Biotechnology · doi:10.1038/nbt.3440 · Cited by 1,061
Emerging 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
Engineering adeno-associated viruses for clinical gene therapy
Kotterman, M. A., & Schaffer, D. V. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3742 · Cited by 761
An essential receptor for adeno-associated virus infection
Pillay, S., Meyer, N. L., Puschnik, A. S., Davulcu, O., Diep, J., Ishikawa, Y., Jae, L. T., Wosen, J. E., Nagamine, C. M., Chapman, M. S., et al. (2016) · Nature · doi:10.1038/nature16465 · Cited by 532
Emerging roles of lncRNA in cancer and therapeutic opportunities.
Jiang, M., Ni, J., Cui, W., Wang, B., & Zhuo, W. (2019) · PubMed · Cited by 502
Viral Vectors for Gene Therapy: Translational and Clinical Outlook
Kotterman, M. A., Chalberg, T. W., & Schaffer, D. V. (2015) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-071813-104938 · Cited by 424
Hepatocyte TAZ/WWTR1 Promotes Inflammation and Fibrosis in Nonalcoholic Steatohepatitis
Wang, X., Zheng, Z., Caviglia, J. M., Corey, K. E., Herfel, T. M., Cai, B., Masia, R., Chung, R. T., Lefkowitch, J. H., Schwabe, R. F., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.016 · Cited by 413
Leborgne, C., Barbon, E., Alexander, J. M., Hanby, H., Delignat, S., Cohen, D. M., Collaud, F., Muraleetharan, S., Lupo, D., Silverberg, J., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0911-7 · Cited by 336
Keeler, A. M., & Flotte, T. R. (2019) · Annual Review of Virology · doi:10.1146/annurev-virology-092818-015530 · Cited by 322
In Silico Reconstruction of the Viral Evolutionary Lineage Yields a Potent Gene Therapy Vector
Zinn, E., Pacouret, S., Khaychuk, V., Turunen, H. T., Carvalho, L. S., Andres-Mateos, E., Shah, S., Shelke, R., Maurer, A. C., Plovie, E., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.07.019 · Cited by 310
“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…”
BackgroundGene therapy for neurological disorders: progress and prospects
Deverman, B. E., Ravina, B. M., Bankiewicz, K. S., Paul, S. M., & Sah, D. W. Y. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.110 · Cited by 306
Hepatocyte-secreted DPP4 in obesity promotes adipose inflammation and insulin resistance
Ghorpade, D. S., Özcan, L., Zheng, Z., Nicoloro, S. M. C., Shen, Y., Chen, E., Blüher, M., Czech, M., & Tabas, I. A. (2018) · Nature · doi:10.1038/nature26138 · Cited by 295
Gene therapy advances: A meta-analysis of AAV usage in clinical settings
Au, H. K. E., Isalan, M., & Mielcarek, M. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2021.809118 · Cited by 284
“However, it transduces human hepatocytes 20-times less efficiently than mouse hepatocytes (37).”
BackgroundInfluentialWeinmann, 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
Promoterless gene targeting without nucleases ameliorates haemophilia B in mice
Barzel, A., Paulk, N. K., Shi, Y., Huang, Y., Chu, K. C., Zhang, F., Valdmanis, P. N., Spector, L. P., Porteus, M. H., Gaensler, K. M. L., et al. (2014) · Nature · doi:10.1038/nature13864 · Cited by 264
Self-citationKörbelin, J., Dogbevia, G., Michelfelder, S., Ridder, D. A., Hunger, A., Wenzel, J., Seismann, H., Lampe, M., Bannach, J., Pasparakis, M., et al. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201506078 · Cited by 253
“The fact that AAV-BR1 and wild-type AAV2 were equally effective in infecting the human hCMEC/D3 cell line (Weksler et al, 2005) might be explained by potential inter-species differences (Lisowski et al, 2014) or, not less likely, by differences between the situation in vivo and in vitro.”
BackgroundInfluentialHepatocyte Notch activation induces liver fibrosis in nonalcoholic steatohepatitis
Zhu, C., Kim, K., Wang, X., Bartolome, A., Salomao, M., Dongiovanni, P., Meroni, M., Graham, M. J., Yates, K. P., Diehl, A. M., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aat0344 · Cited by 250
Erratum: Gene therapy for neurological disorders: progress and prospects
Deverman, B. E., Ravina, B. M., Bankiewicz, K. S., Paul, S. M., & Sah, D. W. Y. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.158 · Cited by 248
Targeting hepatitis B virus cccDNA by CRISPR/Cas9 nuclease efficiently inhibits viral replication
Dong, C., Qu, L., Wang, H., Wei, L., Dong, Y., & Xiong, S. (2015) · Antiviral Research · doi:10.1016/j.antiviral.2015.03.015 · Cited by 245
Multiyear Factor VIII Expression after AAV Gene Transfer for Hemophilia A
George, L. A., Monahan, P. E., Eyster, M. E., Sullivan, S. K., Ragni, M. V., Croteau, S. E., Rasko, J. E. J., Recht, M., Samelson‐Jones, B. J., MacDougall, A., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2104205 · Cited by 248
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
Clinical development of gene therapy: results and lessons from recent successes
Kumar, S. R. P., Markusic, D. M., Biswas, M., High, K. A., & Herzog, R. W. (2016) · Molecular Therapy — Methods & Clinical Development · doi:10.1038/mtm.2016.34 · Cited by 246
Update on clinical gene therapy for hemophilia
Perrin, G. Q., Herzog, R. W., & Markusic, D. M. (2018) · Blood · doi:10.1182/blood-2018-07-820720 · Cited by 187
Drug delivery systems for CRISPR-based genome editors
Madigan, V. J., Zhang, F., & Dahlman, J. E. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00762-x · Cited by 193
“Using humanized mice, whose livers are reconstituted with mouse as well as human hepatocytes, the best AAV in mouse cells was found to differ from the best AAV in human cells 112,113 .”
BackgroundMethodRapid evolution of blood-brain-barrier-penetrating AAV capsids by RNA-driven biopanning
Nonnenmacher, M., Wang, W., Child, M. A., Ren, X.-Q., Huang, C., Ren, A. Z., Tocci, J., Chen, Q., Bittner, K., Tyson, K., et al. (2021) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2020.12.006 · Cited by 168
György, B., Meijer, E. J., Ivanchenko, M. V., Tenneson, K., Émond, F., Hanlon, K. S., Indzhykulian, A. A., Volak, A., Karavitaki, K. D., Tamvakologos, P. I., et al. (2018) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2018.11.003 · Cited by 163
Paulk, N. K., Pekrun, K., Zhu, E., Nygaard, S., Li, B., Xu, J., Chu, K., Leborgne, C., Dane, A. P., Haft, A., et al. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2017.09.021 · Cited by 161
“Please cite this article as: Paulk NK, Pekrun K, Zhu E, Nygaard S, Li B, Xu J, Chu K, Leborgne C, Dane AP, Haft A, Zhang Y, Zhang F, Morton C, Valentine MB, Davidoff AM, Nathwani AC, Mingozzi F, Grompe M, Alexander IE, Lisowski L, Kay MA, Bioengineered AAV capsids with combined high human liver transduction in vivo an…”
Self-citationAdeno-associated virus serotypes for gene therapeutics
Lisowski, L., Tay, S. S., & Alexander, I. E. (2015) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2015.07.006 · Cited by 169
Self-citationThe Balance of Stromal BMP Signaling Mediated by GREM1 and ISLR Drives Colorectal Carcinogenesis
Kobayashi, H., Gieniec, K. A., Wright, J. A., Wang, T., Asai, N., Mizutani, Y., Lida, T., Ando, R., Suzuki, N., Lannagan, T. R. M., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.11.011 · Cited by 158
“23,24 In light of new human liver-tropic bioengineered AAVs, 26 our work suggests that AAV-mediated hepatocyte-directed therapy could, in the future, serve as a novel and well-tolerated cancer therapy.”
Self-citationGenomic investigations of unexplained acute hepatitis in children
Morfopoulou, S., Buddle, S., Montaguth, O. E. T., Atkinson, L., Guerra‐Assunção, J. A., Marjaneh, M. M., Chiozzi, R. Z., Storey, N., Campos, L., Hutchinson, J. C., et al. (2023) · Nature · doi:10.1038/s41586-023-06003-w · Cited by 157
“3b), we generated functional rAAV particles that transduced Huh-7 cells with comparable efficacy to both canonical AAV2 and the synthetic liver-tropic LK03 AAV vector 15 .”
BackgroundRumachik, N. G., Malaker, S. A., Poweleit, N., Maynard, L. H., Adams, C. M., Leib, R. D., Cirolia, G., Thomas, D. R., Stamnes, S. J., Holt, K. H., et al. (2020) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2020.05.018 · Cited by 158
Rezvani, M., Español-Suñer, R., Malato, Y., Dumont, L., Grimm, A. A., Kienle, E., Bindman, J. G., Wiedtke, E., Hsu, B. Y., Naqvi, S. J., et al. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.05.005 · Cited by 150
“For this, technologies like AAV capsid DNA shuffling or peptide display could be used (Grimm 814 Cell Stem Cell 18, 809–816, June 2, 2016 et al., 2008; Lisowski et al., 2014).”
Species-dependent in vivo mRNA delivery and cellular responses to nanoparticles
Hatit, M. Z. C., Lokugamage, M. P., Dobrowolski, C. N., Paunovska, K., Ni, H., Zhao, K., Vanover, D. A., Beyersdorf, J. P., Peck, H. E., Loughrey, D., et al. (2022) · Nature Nanotechnology · doi:10.1038/s41565-021-01030-y · Cited by 158
Adeno-Associated Virus Vectors as Therapeutic and Investigational Tools in the Cardiovascular System
Zacchigna, S., Zentilin, L., & Giacca, M. (2014) · Circulation Research · doi:10.1161/circresaha.114.302331 · Cited by 144
“Similarly, AAV8, which is effective in transducing the liver in many animal models, transduced human hepatocytes in a relatively poor manner.(160) On the contrary, AAV3 efficiently transduced human but not murine hepatocytes.”
BackgroundCRISPR-Cas9 Targeting of PCSK9 in Human Hepatocytes In Vivo—Brief Report
Wang, X., Raghavan, A., Chen, T., Qiao, L., Zhang, Y., Ding, Q., & Musunuru, K. (2016) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.116.307227 · Cited by 146
Self-citationAdeno-Associated Virus Gene Therapy for Liver Disease
Kattenhorn, L. M., Tipper, C. H., Stoica, L., Geraghty, D. S., Wright, T. L., Clark, K. R., & Wadsworth, S. C. (2016) · Human Gene Therapy · doi:10.1089/hum.2016.160 · Cited by 138
Extensive double humanization of both liver and hematopoiesis in FRGN mice
Wilson, E. M., Bial, J., Tarlow, B., Bial, G., Jensen, B., Greiner, D. L., Brehm, M. A., & Grompe, M. (2014) · Stem Cell Research · doi:10.1016/j.scr.2014.08.006 · Cited by 136
“…2001; Bissig et al., 2010; Mercer et al., 2001; Morosan et al., 2006; Vaughan et al., 2012; Kawahara et al., 2013), drug metabolism (Tanoue et al., 2013; Sanoh et al., 2012), gene therapy (Lisowski et al., 2014) and hepatic stem cells (Duncan et al., 2012; Takebe et al., 2013; Zhu et al., 2014).”
Self-citationNovel vectors and approaches for gene therapy in liver diseases
Maestro, S., Weber, N. D., Zabaleta, N., Aldabe, R., & González‐Aseguinolaza, G. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100300 · Cited by 143
Surface-Engineered Viral Vectors for Selective and Cell Type-Specific Gene Delivery
Buchholz, C. J., Friedel, T., & Büning, H. (2015) · Trends in biotechnology · doi:10.1016/j.tibtech.2015.09.008 · Cited by 141
“AAV–LK03, the resulting variant, was composed out of five parental AAV capsids and indeed exhibited a substantially improved tropism for human hepatocytes [57].”
BackgroundRescue of Pompe disease in mice by AAV-mediated liver delivery of secretable acid α-glucosidase
Puzzo, F., Colella, P., Biferi, M. G., Bali, D. S., Paulk, N. K., Vidal, P., Collaud, F., Sola, M. S., Charles, S., Hardet, R., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aam6375 · Cited by 141
“8, D and E), with AAVLK03 showing significantly higher transgene expression compared to AAV8 in human primary hepatocytes (*P < 0.05, AAVLK03 compared to AAV8; Fig.”
BackgroundInfluentialSelf-citationGene Therapy 2017: Progress and Future Directions
Keeler, A. M., ElMallah, M. K., & Flotte, T. R. (2017) · Clinical and Translational Science · doi:10.1111/cts.12466 · Cited by 147
Off-target-free gene delivery by affinity-purified receptor-targeted viral vectors
Münch, R. C., Muth, A., Muik, A., Friedel, T., Schmatz, J., Dreier, B., Trkola, A., Plückthun, A., Büning, H., & Buchholz, C. J. (2015) · Nature Communications · doi:10.1038/ncomms7246 · Cited by 138
The Discovery of Extracellular Vesicles and Their Emergence as a Next-Generation Therapy
Rai, A., Claridge, B., Lozano, J., & Greening, D. W. (2024) · Circulation Research · doi:10.1161/circresaha.123.323054 · Cited by 136
Journey to the Center of the Cell: Tracing the Path of AAV Transduction
Dhungel, B. P., Bailey, C. G., & Rasko, J. E. J. (2021) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.09.010 · Cited by 122
Nanoparticles That Deliver RNA to Bone Marrow Identified by in Vivo Directed Evolution
Sago, C. D., Lokugamage, M. P., Islam, F. Z., Krupczak, B. R., Sato, M., & Dahlman, J. E. (2018) · Journal of the American Chemical Society · doi:10.1021/jacs.8b08976 · Cited by 132
Adeno-associated virus: fit to serve
Zinn, E. M., & Vandenberghe, L. H. (2014) · Current Opinion in Virology · doi:10.1016/j.coviro.2014.07.008 · Cited by 123
Neuroligin-4 Regulates Excitatory Synaptic Transmission in Human Neurons
Marro, S. G., Chanda, S., Yang, N., Janas, J. A., Valperga, G., Trotter, J. H., Zhou, B., Merrill, S. A., Yousif, I., Shelby, H., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.05.043 · Cited by 120
Weber, N. D., Stone, D., Sedlak, R. H., Feelixge, H. S. D. S., Roychoudhury, P., Schiffer, J. T., Aubert, M., & Jerome, K. R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0097579 · Cited by 122
Superior In vivo Transduction of Human Hepatocytes Using Engineered AAV3 Capsid
Vercauteren, K., Hoffman, B. E., Zolotukhin, I., Keeler, G. D., Xiao, J. W., Basner-Tschakarjan, E., High, K. A., Ertl, H. C., Rice, C. M., Srivastava, A., et al. (2016) · Molecular Therapy · doi:10.1038/mt.2016.61 · Cited by 114
In Vivo Selection Yields AAV-B1 Capsid for Central Nervous System and Muscle Gene Therapy
Choudhury, S., Fitzpatrick, Z., Harris, A. F., Maitland, S. A., Ferreira, J. S., Zhang, Y., Ma, S., Sharma, R. B., Gray‐Edwards, H. L., Johnson, J. A., et al. (2016) · Molecular Therapy · doi:10.1038/mt.2016.84 · Cited by 118
Self-citationZhang, Z., Marro, S. G., Zhang, Y., Arendt, K. L., Patzke, C., Zhou, B., Fair, T., Yang, N., Südhof, T. C., Wernig, M., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aar4338 · Cited by 110
Self-citationEngineering the AAV capsid to optimize vector–host-interactions
Büning, H., Huber, A., Zhang, L. N., Meumann, N., & Hacker, U. T. (2015) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2015.08.002 · Cited by 119
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
“AAV capsids can be improved through rational design, directed evolution techniques and in vivo selection in mouse or humanized mouse models (Asokan et al., 2010; Shen et al., 2013; Kotterman and Schaffer, 2014; Lisowski et al., 2014; Tervo et al., 2016; Kanaan et al., 2017).”
BackgroundBaruteau, J., Waddington, S. N., Alexander, I. E., & Gissen, P. (2017) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-017-0053-3 · Cited by 111
“This approach is paying off by generating re-engineered AAV variants with increased transduction efficiency in primary human hepatocytes (Lisowski et al 2014).”
BackgroundSelf-citationOptogenetic approaches to vision restoration
Simunovic, M. P., Shen, W., Lin, J. Y., Protti, D. A., Lisowski, L., & Gillies, M. C. (2018) · Experimental Eye Research · doi:10.1016/j.exer.2018.09.003 · Cited by 111
Self-citationGrimm, D., & Zolotukhin, S. (2015) · Molecular Therapy · doi:10.1038/mt.2015.173 · Cited by 108
Wang, L., Bell, P. L., Somanathan, S., Wang, Q., He, Z., Yu, H., McMenamin, D., Goode, T. L., Calcedo, R., & Wilson, J. M. (2015) · Molecular Therapy · doi:10.1038/mt.2015.179 · Cited by 106
Logan, G. J., Dane, A. P., Hallwirth, C. V., Smyth, C. M., Wilkie, E. E., Amaya, A. K., Zhu, E., Khandekar, N., Ginn, S. L., Liao, S. H. Y., et al. (2017) · Nature Genetics · doi:10.1038/ng.3893 · Cited by 105
Self-citationWesthaus, A., Cabanes-Creus, M., Rybicki, A., Baltazar, G., Navarro, R. G., Zhu, E., Drouyer, M., Knight, M., Albu, R. F., Ng, B. H., et al. (2020) · Human Gene Therapy · doi:10.1089/hum.2019.264 · Cited by 102
Self-citationCrosstalk of lncRNA and Cellular Metabolism and Their Regulatory Mechanism in Cancer
Lin, Y.-H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21082947 · Cited by 103
“After large-scale screening, ideal AAV systems have been developed to target human cancer cells [113].”
BackgroundAdeno-associated virus 2 bound to its cellular receptor AAVR
Zhang, R., Cao, L., Cui, M., Sun, Z., Hu, M., Zhang, R., Stuart, W. S., Zhao, X., Yang, Z., Li, X., et al. (2019) · Nature Microbiology · doi:10.1038/s41564-018-0356-7 · Cited by 108
Exposure to wild-type AAV drives distinct capsid immunity profiles in humans
Kuranda, K., Jean-Alphonse, P., Leborgne, C., Hardet, R., Collaud, F., Marmier, S., Costa Verdera, H., Ronzitti, G., Veron, P., & Mingozzi, F. (2018) · Journal of Clinical Investigation · doi:10.1172/jci122372 · Cited by 104
“We used the AAV8 serotype, which is highly homologous to AAV2 (49) but has a greater capacity to transduce murine hepatocytes (50).”
MethodSystemic delivery of adeno-associated viral vectors
Duan, D. (2016) · Current Opinion in Virology · doi:10.1016/j.coviro.2016.07.006 · Cited by 105
Nienhuis, A. W., Nathwani, A. C., & Davidoff, A. M. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.03.033 · Cited by 103
CRISPR-Cas9 gene editing of hepatitis B virus in chronically infected humanized mice
Stone, D., Long, K. R., Loprieno, M. A., Feelixge, H. S. D. S., Kenkel, E. J., Liley, R. M., Rapp, S., Roychoudhury, P., Nguyen, T., Stensland, L., et al. (2020) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2020.11.014 · Cited by 98
Gene therapy for hemophilia: what does the future hold?
Doshi, B. S., & Arruda, V. R. (2018) · Therapeutic Advances in Hematology · doi:10.1177/2040620718791933 · Cited by 101
Gene Therapy for the Nervous System: Challenges and New Strategies
Maguire, C. A., Ramirez, S. H., Merkel, S. F., Sena‐Esteves, M., & Breakefield, X. O. (2014) · Neurotherapeutics · doi:10.1007/s13311-014-0299-5 · Cited by 99
Using a barcoded AAV capsid library to select for clinically relevant gene therapy vectors
Pekrun, K., de Alencastro, G., Luo, Q.-J., Liu, J., Kim, Y., Nygaard, S. C., Galivo, F., Zhang, F., Song, R., Tiffany, M. R., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.131610 · Cited by 98
Self-citationErtl, H. C. J., & High, K. A. (2017) · Human Gene Therapy · doi:10.1089/hum.2016.172 · Cited by 94
“38,39 In these mice, rAAV8 and 9 vectors showed higher transduction of mouse hepatocytes compared with a capsid modified AAV3 vector, which in turn was superior in transducing human hepatocytes.”
The Promise and Challenge of In Vivo Delivery for Genome Therapeutics
Wilson, R. C., & Gilbert, L. A. (2017) · ACS Chemical Biology · doi:10.1021/acschembio.7b00680 · Cited by 98
Körbelin, J., Sieber, T., Michelfelder, S., Lunding, L. P., Spies, E., Hunger, A., Alawi, M., Rapti, K., Indenbirken, D., Müller, O. J., et al. (2016) · Molecular Therapy · doi:10.1038/mt.2016.62 · Cited by 91
Advances with RNAi-Based Therapy for Hepatitis B Virus Infection
van den Berg, F. T., Limani, S. W., Mnyandu, N., Maepa, M. B., Ely, A., & Arbuthnot, P. B. (2020) · Viruses · doi:10.3390/v12080851 · Cited by 91
“An example of directed evolution entailed use of mutated capsids, generated by DNA shuffling, which were exposed to rounds of selective pressure by neutralizing antibodies [119,122].”
BackgroundAAV vector development, back to the future
Suárez-Amarán, L., Song, L., Tretiakova, A. P., Mikhail, S., & Samulski, R. J. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.03.064 · Cited by 98
“93,94 The "shuffling approach" has undergone continuous refinement for over 2 decades.”
Adeno-associated Virus as a Mammalian DNA Vector
Salganik, M., Hirsch, M. L., & Samulski, R. J. (2015) · Microbiology Spectrum · doi:10.1128/microbiolspec.mdna3-0052-2014 · Cited by 93
“…have taken a more holistic directed evolution approach by generating libraries of novel AAV sequences either by random mutagenesis (100 – 102) or shuf fl ing of capsid sequences across multiple serotypes followed by selection on either a target cell population (99, 103 – 107) or in vivo (108 – 113).”
BackgroundTargeting hepatitis B virus cccDNA using CRISPR/Cas9
Kennedy, E. M., Kornepati, A. V. R., & Cullen, B. R. (2015) · Antiviral Research · doi:10.1016/j.antiviral.2015.10.004 · Cited by 86
Shi, H., Wang, X., Li, F., Gerlach, B. D., Yurdagul, A., Moore, M. P., Zeldin, S., Zhang, H., Cai, B., Zheng, Z., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abp8309 · Cited by 85
“We conducted another experiment in which we treated steatotic mice with AAV8-H1-shCD47 (shCD47) to silence CD47 in hepatocytes (34, 46).”
MethodState-of-the-art human gene therapy: part I. Gene delivery technologies.
Wang, D., & Gao, G. (2014) · PubMed · Cited by 87
Monahan, P. E., Négrier, C., Tarantino, M. D., Valentino, L. A., & Mingozzi, F. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10112471 · Cited by 87
“Strategies under evaluation in preclinical models and clinical trials include maximizing vector potency to decrease the therapeutic dose and the risk of immune-mediated toxicity, as well as increasing target cell transduction efficiency [96,97], transgene expression levels [44], or transgene activity [11,43].”
BackgroundChen, W., Yao, S., Wan, J., Tian, Y., Huang, L., Wang, S., Akter, F., Wu, Y., Yao, Y., & Zhang, X. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.03.029 · Cited by 81
Testing thousands of nanoparticles in vivo using DNA barcodes
Lokugamage, M. P., Sago, C. D., & Dahlman, J. E. (2018) · Current Opinion in Biomedical Engineering · doi:10.1016/j.cobme.2018.08.001 · Cited by 84
Liver induced transgene tolerance with AAV vectors
Keeler, G. D., Markusic, D. M., & Hoffman, B. E. (2019) · Cellular Immunology · doi:10.1016/j.cellimm.2017.12.002 · Cited by 81
Age-Related Seroprevalence of Antibodies Against AAV-LK03 in a UK Population Cohort
Perocheau, D. P., Cunningham, S. C., Lee, J., Antinao Diaz, J., Waddington, S. N., Gilmour, K., Eaglestone, S., Lisowski, L., Thrasher, A. J., Alexander, I. E., et al. (2019) · Human Gene Therapy · doi:10.1089/hum.2018.098 · Cited by 81
Self-citationBecker, J., Fakhiri, J., & Grimm, D. (2022) · Pathogens · doi:10.3390/pathogens11070756 · Cited by 88
“Removing this threonine in AAV-KP1, or adding it to AAV3B or AAV-LK03, allowed the authors to disable or enable the transduction of murine vs. human hepatocytes in a hFRG xenograft mouse model, respectively.”
BackgroundHuang, Q., Chen, A. T., Chan, K. Y., Sorensen, H., Barry, A. J., Azari, B., Zheng, Q., Beddow, T., Zhao, B., Tobey, I. G., et al. (2023) · PLoS Biology · doi:10.1371/journal.pbio.3002112 · Cited by 85
Han, S.-O., Ronzitti, G., Arnson, B., Leborgne, C., Li, S., Mingozzi, F., & Koeberl, D. (2017) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2016.12.010 · Cited by 78
Li, S., Ling, C., Li, Z., Li, M., Su, Q., He, R., Tang, Q., Greiner, D. L., Shultz, L. D., Brehm, M. A., et al. (2015) · Molecular Therapy · doi:10.1038/mt.2015.174 · Cited by 80
Somatic Correction of Junctional Epidermolysis Bullosa by a Highly Recombinogenic AAV Variant
Melo, S. P., Lisowski, L., Bashkirova, E., Zhen, H. H., Chu, K. C., Keene, D. R., Marinkovich, M. P., Kay, M. A., & Oro, A. E. (2014) · Molecular Therapy · doi:10.1038/mt.2013.290 · Cited by 76
Self-citationChowdhury, E. A., Meno‐Tetang, G. M. L., Chang, H. Y., Wu, S., Huang, H. W., Jamier, T., Chandran, J. S., & Shah, D. K. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.01.017 · Cited by 80
Enzyme-Responsive Charge-Reversal Polymer-Mediated Effective Gene Therapy for Intraperitoneal Tumors
Qiu, N., Gao, J., Liu, Q., Wang, J., & Shen, Y. (2018) · Biomacromolecules · doi:10.1021/acs.biomac.8b00440 · Cited by 78
Gene therapy for liver diseases — progress and challenges
Zabaleta, N., Unzu, C., Weber, N. D., & González‐Aseguinolaza, G. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-022-00729-0 · Cited by 78
Systematic multi-trait AAV capsid engineering for efficient gene delivery
Eid, F.-E., Chen, A. T., Chan, K. Y., Huang, Q., Zheng, Q., Tobey, I. G., Pacouret, S., Brauer, P. P., Keyes, C., Powell, M. M., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-50555-y · Cited by 85
“Previous efforts to develop capsids with improved human hepatocyte transduction have generated candidates that are selective for human hepatocytes but inef fi ciently transduce the mouse liver in vivo 2,15 .”
A Positive Feedback Loop of TET3 and TGF-β1 Promotes Liver Fibrosis
Xu, Y., Sun, X., Zhang, R., Cao, T., Cai, S.-Y., Boyer, J. L., Zhang, X., Li, D., & Huang, Y. (2020) · Cell Reports · doi:10.1016/j.celrep.2019.12.092 · Cited by 73
“Since AAV8 targets mainly hepatocytes (Davidoff et al., 2005; Lisowski et al., 2014; Rezvani et al., 2016), our results provide strong in vivo evidence supporting cross-talk between hepatocytes and HSCs via the TET3/ TGF-β loop in regulation of liver fibrosis (Figure 3I).”
BackgroundAdeno-associated viral vectors for the treatment of hemophilia
High, K. A., & Anguela, X. M. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv475 · Cited by 77
Cardiac gene therapy with adeno-associated virus-based vectors
Chamberlain, K., Riyad, J. M., & Weber, T. (2017) · Current Opinion in Cardiology · doi:10.1097/hco.0000000000000386 · Cited by 75
tRNA therapeutics for genetic diseases
Coller, J., & Ignatova, Z. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00829-9 · Cited by 72
“In seven clinical trials, AAV8 and AAV9 capsids are used for delivery to the CNS. Capsid evolution techniques are becoming increasingly sophisticated, enabling highly specific transduction of specific cell types.”
Marsic, D., Govindasamy, L., Currlin, S., Markusic, D. M., Tseng, Y.-S., Herzog, R. W., Agbandje‐McKenna, M., & Zolotukhin, S. (2014) · Molecular Therapy · doi:10.1038/mt.2014.139 · Cited by 75
Metadata
- Authors
- 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.
- Affiliations
- Salk Institute for Biological Studies (US)
- Stanford Medicine (US)
- Children's Medical Research Institute (AU)
- Yecuris (United States) (US)
- Oregon Health & Science University (US)
- The University of Sydney (AU)
- Corresponding author
- Kay, Mark A.
- ORCID
- Venue
- Nature
- Published
- 2013-12-25
- Volume
- 506
- Issue
- 7488
- Pages
- 382-386
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3939040
- OpenAlex
- W1981950767
- Cited by
- 450
- References
- 36
- Citations by year
- 2026: 20 · 2025: 28 · 2024: 36 · 2023: 39 · 2022: 45 · 2021: 34 · 2020: 42 · 2019: 36 · 2018: 32 · 2017: 41 · 2016: 35 · 2015: 46 · 2014: 14 · 2013: 1
- FWCI
- 21.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL064274, HL092096, R01HL092096, R01HL064274)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK048252, DK048252)
- 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
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- recombinant adeno-associated virus, AAV serotype 2, xenotransplantation, DNA shuffling, gene therapy vectors
- MeSH terms
- Dependovirus, Animals, Capsid, Cells, Cultured, Chimera, Clinical Trials as Topic, Disease Models, Animal, Female, Genetic Vectors, Carcinoma, Hepatocellular, Humans, Liver, Male, Species Specificity, Transduction, Genetic, Genetic Therapy, Transgenes, Hepatocytes, Capsid Proteins, Cell Line, Tumor, Mice, Heterografts
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