Trans-splicing vectors expand the utility of adeno-associated virus for gene therapy
Open accessAbstract
Adeno-associated viral (AAV) vectors have demonstrated considerable promise for gene therapy of inherited diseases. However, with a packaging size of <5 kb, applications have been limited to relatively small disease genes. Based on the finding that AAV genomes undergo intermolecular circular concatamerization after transduction in muscle, we have developed a paradigm to increase the size of delivered transgenes with this vector through trans-splicing between two independent vectors coadministered to the same tissue. When two vectors encoding either the 5′ or 3′ portions of the erythropoietin genomic locus were used, functional erythropoietin protein was expressed in muscle subsequent to the formation of intermolecular circular concatamers in a head-to-tail orientation through trans-splicing between these two independent vector genomes. These findings will allow for the application of AAV technologies to a wider variety of diseases for which therapeutic transgenes exceed the packaging limitation of present AAV vectors.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Split vector systems exploiting head-to-tail concatamerization have been developed to circumvent the small packaging capacity of AAV genomes.
“Recently, split vector systems, exploiting head-to-tail concatamerization formation, have been developed to circumvent the small packaging capacity of AAV genomes (13-16, 41, 52).”
From Packaging Capacity of Adeno-Associated Virus Serotypes: Impact of Larger Genomes on Infectivity and Postentry Steps (2005) · cites this paper as [52]
The trans-splicing method to expand the size of ORFs that can be successfully expressed using AAV vectors was originally developed in the laboratory of John Engelhardt and has since been utilized in several studies with varying success.
“The trans-splicing method to expand the size of ORFs that can be successfully expressed using AAV vectors was originally developed in the laboratory of John Engelhardt 52,53 and has since been utilized in several studies with varying success (e.g., refs. 53-57 ).”
From Expressing Transgenes That Exceed the Packaging Capacity of Adeno-Associated Virus Capsids (2016) · cites this paper as [53]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Summerford, C., & Samulski, R. J. (1998) · Journal of Virology · doi:10.1128/jvi.72.2.1438-1445.1998 · Cited by 1,409 · see citing works
Use of Adeno-Associated Virus as a General Transduction Vector for Mammalian Cells
Muzyczka, N. (1992) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-75608-5_5 · Cited by 756 · see citing works
αVβ5 integrin: a co-receptor for adeno-associated virus type 2 infection
Summerford, C., Bartlett, J. S., & Samulski, R. J. (1999) · Nature Medicine · doi:10.1038/4768 · Cited by 711 · see citing works
Duan, D., Sharma, P., Yang, J., Yue, Y., Dudus, L., Zhang, Y., Fisher, K. J., & Engelhardt, J. F. (1998) · Journal of Virology · doi:10.1128/jvi.72.11.8568-8577.1998 · Cited by 522 · see citing works
Self-citationSamulski, R. J., Chang, L., & Shenk, T. E. (1987) · Journal of Virology · doi:10.1128/jvi.61.10.3096-3101.1987 · Cited by 449 · see citing works
Human fibroblast growth factor receptor 1 is a co-receptor for infection by adeno-associated virus 2
Qing, K., Mah, C., Hansen, J., Zhou, S., Dwarki, V., & Srivastava, A. (1999) · Nature Medicine · doi:10.1038/4758 · Cited by 443 · see citing works
Animal Model of Adenine-Induced Chronic Renal Failure in Rats
Yokozawa, T., Zheng, P., Oura, H., & Koizumi, F. (2008) · The Nephron journals/Nephron journals · doi:10.1159/000183992 · Cited by 356 · see citing works
Biology of Adeno-associated Virus
Berns, K. I., & Giraud, C. (1996) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-80207-2_1 · Cited by 308 · see citing works
Clark, K. R., Liu, X., McGrath, J. P., & Johnson, P. R. (1999) · Human Gene Therapy · doi:10.1089/10430349950018427 · Cited by 306 · see citing works
Yang, J., Zhou, W., Zhang, Y., Zidon, T. M., Ritchie, T. L., & Engelhardt, J. F. (1999) · Journal of Virology · doi:10.1128/jvi.73.11.9468-9477.1999 · Cited by 201 · see citing works
Self-citationAdeno-associated virus vectors
Carter, B. J. (1992) · Current Opinion in Biotechnology · doi:10.1016/0958-1669(92)90082-t · Cited by 160 · see citing works
Structural Analysis of Adeno-Associated Virus Transduction Circular Intermediates
Duan, D., Yan, Z., Yue, Y., & Engelhardt, J. F. (1999) · Virology · doi:10.1006/viro.1999.9821 · Cited by 100 · see citing works
Self-citationDuan, D., Sharma, P., Dudus, L., Zhang, Y., Şanlıoğlu, S., Yan, Z., Yue, Y., Ye, Y., Lester, R., Yang, J., et al. (1999) · Journal of Virology · doi:10.1128/jvi.73.1.161-169.1999 · Cited by 91 · see citing works
Self-citationSanlioglu, S., Duan, D.-S., & Engelhardt, J. F. (1999) · Human Gene Therapy · doi:10.1089/10430349950018661 · Cited by 70 · see citing works
Self-citationRegulation of red blood cell production
Adamson, J. W. (1996) · The American Journal of Medicine · doi:10.1016/s0002-9343(96)00160-x · Cited by 46 · see citing works
Structural and functional heterogeneity of integrated recombinant AAV genomes
Duan, D., Fisher, K. J., Burda, J. F., & Engelhardt, J. F. (1997) · Virus Research · doi:10.1016/s0168-1702(96)01425-6 · Cited by 45 · see citing works
Self-citationAdeno-Associated Virus (AAV) Vectors in Gene Therapy
(1996) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-80207-2 · Cited by 36 · see citing works
Effect of chronic renal failure on the expression of erythropoietin message in a murine model.
Zhang, F., Laneuville, P., Gagnon, R. F., Morin, B., & Brox, A. G. (1996) · PubMed · Cited by 19 · see citing works
Qu, N., Wen, J. K., & Li, E. (1995) · PubMed · Cited by 1 · see citing works
Flagged first, then by citations
1 of the 20 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- [16]Qu N, Wen J K, Li E. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih. 1995;15:222–224. [Google Scholar]
- [18]Zhang F, Laneuville P, Gagnon R F, Morin B, Brox A G. Exp Hematol. 1996;24:1469–1474. [PubMed] [Google Scholar]
Cited by
Sorted by citations
Viral vectors for gene therapy: the art of turning infectious agents into vehicles of therapeutics
Kay, M., Glorioso, J., & Naldini, L. (2001) · Nature Medicine · doi:10.1038/83324 · Cited by 1,444 · see citing works
Effect of genome size on AAV vector packaging
Wu, Z., Yang, H., & Colosi, P. (2010) · Molecular Therapy · doi:10.1038/mt.2009.255 · Cited by 1,025 · see citing works
Gene therapy using adeno-associated virus vectors
Daya, S., & Berns, K. I. (2008) · Clinical Microbiology Reviews · doi:10.1128/cmr.00008-08 · Cited by 926 · see citing works
Gene therapy: trials and tribulations
Somia, N. V., & Verma, I. M. (2000) · Nature Reviews Genetics · doi:10.1038/35038533 · Cited by 711 · see citing works
Integration of Adeno-Associated Virus (AAV) and Recombinant AAV Vectors
McCarty, D. M., Young, S. M., & Samulski, R. J. (2004) · Annual Review of Genetics · doi:10.1146/annurev.genet.37.110801.143717 · Cited by 450 · see citing works
Grieger, J. C., & Samulski, R. J. (2005) · Journal of Virology · doi:10.1128/jvi.79.15.9933-9944.2005 · Cited by 419 · see citing works
AAV vectors: The Rubik’s cube of human gene therapy
Pupo, A., Fernández, A., Low, S. H., François, A., Suárez-Amarán, L., & Samulski, R. J. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.09.015 · Cited by 361 · see citing works
Gene Therapy: Promises and Problems
Pfeifer, A., & Verma, I. M. (2001) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.2.1.177 · Cited by 344 · see citing works
Keeler, A. M., & Flotte, T. R. (2019) · Annual Review of Virology · doi:10.1146/annurev-virology-092818-015530 · Cited by 322 · see citing works
Clark, K. R., Liu, X., McGrath, J. P., & Johnson, P. R. (1999) · Human Gene Therapy · doi:10.1089/10430349950018427 · Cited by 306 · see citing works
Regulatable gene expression systems for gene therapy applications: progress and future challenges
Goverdhana, S., Puntel, M., Xiong, W., Zirger, J. M., Barcia, C., Curtin, J. F., Soffer, E. B., Mondkar, S., King, G. D., Hu, J., et al. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2005.03.022 · Cited by 283 · see citing works
Viral vectors for gene delivery to the central nervous system
Lentz, T. B., Gray, S. J., & Samulski, R. J. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.09.014 · Cited by 274 · see citing works
Effective delivery of large genes to the retina by dual AAV vectors
Trapani, I., Colella, P., Sommella, A., Iodice, C., Cesi, G., de Simone, S., Marrocco, E., Rossi, S., Giunti, M., Palfi, A., et al. (2014) · EMBO Molecular Medicine · doi:10.1002/emmm.201302948 · Cited by 269 · see citing works
Duan, D., Yue, Y., & Engelhardt, J. F. (2001) · Molecular Therapy · doi:10.1006/mthe.2001.0456 · Cited by 262 · see citing works
Self-citationFlotte, T. R., Zeitlin, P. L., Reynolds, T. C., Heald, A. E., Pedersen, P. S., Beck, S. E., Conrad, C., Brass‐Ernst, L., Humphries, M. R., Sullivan, K., et al. (2003) · Human Gene Therapy · doi:10.1089/104303403322124792 · Cited by 244 · see citing works
Al‐Moyed, H., Cepeda, A. P., Jung, S., Moser, T., Kügler, S., & Reisinger, E. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201809396 · Cited by 230 · see citing works
Adeno-associated virus vectors for gene therapy: more pros than cons?
Monahan, P. E., & Samulski, R. J. (2000) · Molecular Medicine Today · doi:10.1016/s1357-4310(00)01810-4 · Cited by 228 · see citing works
Basic Biology of Adeno-Associated Virus (AAV) Vectors Used in Gene Therapy
Balakrishnan, B., & Jayandharan, G. (2014) · Current Gene Therapy · doi:10.2174/1566523214666140302193709 · Cited by 225 · see citing works
Efficient in vivo gene expression by trans-splicing adeno-associated viral vectors
Lai, Y., Yue, Y., Liu, M., Ghosh, A., Engelhardt, J. F., Chamberlain, J. S., & Duan, D. (2005) · Nature Biotechnology · doi:10.1038/nbt1153 · Cited by 224 · see citing works
Self-citationYan, Z., Zak, R., Luxton, G. W. G., Ritchie, T. C., Bantel-Schaal, U., & Engelhardt, J. F. (2002) · Journal of Virology · doi:10.1128/jvi.76.5.2043-2053.2002 · Cited by 222 · see citing works
Self-citationVorburger, S. A., & Hunt, K. K. (2002) · The Oncologist · doi:10.1634/theoncologist.7-1-46 · Cited by 220 · see citing works
Total correction of hemophilia A mice with canine FVIII using an AAV 8 serotype
Sarkar, R., Tetreault, R., Gao, G., Wang, L., Bell, P. L., Chandler, R. J., Wilson, J. M., & Kazazian, H. H. (2003) · Blood · doi:10.1182/blood-2003-08-2954 · Cited by 201 · see citing works
Tornabene, P., Trapani, I., Minopoli, R., Centrulo, M., Lupo, M., de Simone, S., Tiberi, P., Dell’Aquila, F., Marrocco, E., Iodice, C., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aav4523 · Cited by 192 · see citing works
Viral vectors for therapy of neurologic diseases
Choudhury, S. R., Hudry, E., Maguire, C. A., Sena-Esteves, M., Breakefield, X. O., & Grandi, P. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.02.013 · Cited by 190 · see citing works
Vector platforms for gene therapy of inherited retinopathies
Trapani, I., Puppo, A., & Auricchio, A. (2014) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2014.08.001 · Cited by 184 · see citing works
Adenovirus and Adeno-Associated Virus Vectors
Lai, C. –., Lai, Y. K. Y., & Rakoczy, P. E. (2002) · DNA and Cell Biology · doi:10.1089/104454902762053855 · Cited by 176 · see citing works
Gene Transfer to Salivary Glands
Baum, B. J., Wellner, R. B., & Zheng, C. (2002) · International review of cytology · doi:10.1016/s0074-7696(02)13013-0 · Cited by 175 · see citing works
Efficient recovery of dysferlin deficiency by dual adeno-associated vector-mediated gene transfer
Lostal, W., Bartoli, M., Bourg, N., Roudaut, C., Bentaïb, A., Miyake, K., Guerchet, N., Fougerousse, F., McNeil, P., & Richard, I. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq065 · Cited by 173 · see citing works
Kwon, I., & Schaffer, D. V. (2007) · Pharmaceutical Research · doi:10.1007/s11095-007-9431-0 · Cited by 164 · see citing works
Ghosh, A., Yue, Y., Lai, Y., & Duan, D. (2008) · Molecular Therapy · doi:10.1038/sj.mt.6300322 · Cited by 161 · see citing works
Self-citationGene Therapy Tools for Brain Diseases
Ingusci, S., Verlengia, G., Soukupova, M., Zucchini, S., & Simonato, M. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00724 · Cited by 158 · see citing works
Treatment of human disease by adeno-associated viral gene transfer
Warrington, K. H., & Herzog, R. W. (2006) · Human Genetics · doi:10.1007/s00439-006-0165-6 · Cited by 155 · see citing works
Animal models for muscular dystrophy: valuable tools for the development of therapies
Allamand, V. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.16.2459 · Cited by 150 · see citing works
Expressing Transgenes That Exceed the Packaging Capacity of Adeno-Associated Virus Capsids
Chamberlain, K., Riyad, J. M., & Weber, T. (2016) · Human Gene Therapy Methods · doi:10.1089/hgtb.2015.140 · Cited by 141 · see citing works
Adeno-Associated Virus Biology
Weitzman, M. D., & Linden, R. M. (2012) · Methods in Molecular Biology · doi:10.1007/978-1-61779-370-7_1 · Cited by 132 · see citing works
Precise hit: adeno-associated virus in gene targeting
Vasileva, A., & Jessberger, R. (2005) · Nature Reviews Microbiology · doi:10.1038/nrmicro1266 · Cited by 148 · see citing works
Dyka, F. M., Boye, S. L., Chiodo, V. A., Hauswirth, W. W., & Boye, S. E. (2014) · Human Gene Therapy Methods · doi:10.1089/hgtb.2013.212 · Cited by 128 · see citing works
Triple Vectors Expand AAV Transfer Capacity in the Retina
Maddalena, A., Tornabene, P., Tiberi, P., Minopoli, R., Manfredi, A., Mutarelli, M., Rossi, S., Simonelli, F., Naggert, J. K., Cacchiarelli, D., et al. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2017.11.019 · Cited by 128 · see citing works
Biomaterial-guided delivery of gene vectors for targeted articular cartilage repair
Cucchiarini, M., & Madry, H. (2018) · Nature Reviews Rheumatology · doi:10.1038/s41584-018-0125-2 · Cited by 128 · see citing works
Adeno-associated Virus Vectors in Gene Therapy
Mary, B., Khan, N., Arumugam, S., Saxena, H., Kumar, M., Manimaran, P., Chattopadhyay, S., & Jayandharan, G. R. (2018) · Springer eBooks · doi:10.1007/978-981-13-0481-1_2 · Cited by 124 · see citing works
Halbert, C. L., Allen, J. M., & Miller, A. D. (2002) · Nature Biotechnology · doi:10.1038/nbt0702-697 · Cited by 121 · see citing works
Clinical applications of retinal gene therapy
Lipinski, D. M., Thake, M., & MacLaren, R. E. (2012) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2012.09.001 · Cited by 122 · see citing works
Adeno-Associated Viral Vectors in Neuroscience Research
Haggerty, D. L., Grecco, G. G., Reeves, K. C., & Atwood, B. K. (2019) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2019.11.012 · Cited by 123 · see citing works
Protein Trans -Splicing as a Means for Viral Vector-Mediated In Vivo Gene Therapy
Li, J., Sun, W., Wang, B., Xiao, X., & Liu, X. (2008) · Human Gene Therapy · doi:10.1089/hum.2008.009 · Cited by 115 · see citing works
Adeno-Associated Virus Structural Biology as a Tool in Vector Development
Drouin, L. M., & Agbandje-McKenna, M. (2013) · Future Virology · doi:10.2217/fvl.13.112 · Cited by 114 · see citing works
Adeno-associated virus vectors: potential applications for cancer gene therapy
Li, C., Bowles, D. E., Dyke, T. V., & Samulski, R. J. (2005) · Cancer Gene Therapy · doi:10.1038/sj.cgt.7700876 · Cited by 110 · see citing works
Wu, J., Zhao, W., Zhong, L., Han, Z., Li, B., Ma, W., Weigel-Kelley, K. A., Warrington, K. H., & Srivastava, A. (2007) · Human Gene Therapy · doi:10.1089/hum.2006.088 · Cited by 108 · see citing works
Yan, Z., Zak, R., Zhang, Y., & Engelhardt, J. F. (2005) · Journal of Virology · doi:10.1128/jvi.79.1.364-379.2005 · Cited by 107 · see citing works
Self-citationOstedgaard, L. S., Rokhlina, T., Karp, P. H., Lashmit, P., Afione, S., Schmidt, M., Zabner, J., Stinski, M. F., Chiorini, J. A., & Welsh, M. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409845102 · Cited by 105 · see citing works
Efficient gene delivery to the cone-enriched pig retina by dual AAV vectors
Colella, P., Trapani, I., Cesi, G., Sommella, A., Manfredi, A., Puppo, A., Iodice, C., Rossi, S., Simonelli, F., Giunti, M., et al. (2014) · Gene Therapy · doi:10.1038/gt.2014.8 · Cited by 103 · see citing works
Fitzsimons, H. L., Bland, R. J., & During, M. J. (2002) · Methods · doi:10.1016/s1046-2023(02)00227-x · Cited by 101 · see citing works
Correction of muscular dystrophies by CRISPR gene editing
Chemello, F., Bassel‐Duby, R., & Olson, E. N. (2020) · Journal of Clinical Investigation · doi:10.1172/jci136873 · Cited by 101 · see citing works
Adeno-associated Virus (AAV) Dual Vector Strategies for Gene Therapy Encoding Large Transgenes.
McClements, M. E., & MacLaren, R. E. (2017) · PubMed Central · Cited by 95 · see citing works
Reich, S. J., Auricchio, A., Hildinger, M., Glover, E., Maguire, A. M., Wilson, J. M., & Bennett, J. (2003) · Human Gene Therapy · doi:10.1089/10430340360464697 · Cited by 96 · see citing works
Murphy, S. L., & High, K. (2008) · British Journal of Haematology · doi:10.1111/j.1365-2141.2007.06942.x · Cited by 57 · see citing works
AAV 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 87 · see citing works
Evaluating 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
Virus-Based Gene Delivery Systems
Mah, C. S., Byrne, B. J., & Flotte, T. R. (2002) · Clinical Pharmacokinetics · doi:10.2165/00003088-200241120-00001 · Cited by 85 · see citing works
Rate Limiting Steps of AAV Transduction and Implications for Human Gene Therapy
Şanlıoğlu, S., Monick, M. M., Lüleci, G., Hunninghake, G. W., & Engelhardt, J. F. (2001) · Current Gene Therapy · doi:10.2174/1566523013348788 · Cited by 85 · see citing works
Self-citationDuan, D., Yan, Z., Yue, Y., Ding, W., & Engelhardt, J. F. (2001) · Journal of Virology · doi:10.1128/jvi.75.16.7662-7671.2001 · Cited by 85 · see citing works
Self-citationmRNA trans-splicing dual AAV vectors for (epi)genome editing and gene therapy
Riedmayr, L. M., Hinrichsmeyer, K. S., Thalhammer, S. B., Mittas, D. M., Karguth, N., Otify, D. Y., Böhm, S., Weber, V. J., Bartoschek, M. D., Splith, V., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-42386-0 · Cited by 87 · see citing works
Understanding Capsid Assembly and Genome Packaging for Adeno-Associated Viruses
Bennett, A., Mietzsch, M., & Agbandje-McKenna, M. (2017) · Future Virology · doi:10.2217/fvl-2017-0011 · Cited by 82 · see citing works
Gene therapy for retinal disease
McClements, M. E., & MacLaren, R. E. (2013) · Translational Research · doi:10.1016/j.trsl.2012.12.007 · Cited by 80 · see citing works
Kodippili, K., Hakim, C. H., Pan, X., Yang, H. T., Yue, Y., Zhang, Y., Shin, J., Yang, N. N., & Duan, D. (2017) · Human Gene Therapy · doi:10.1089/hum.2017.095 · Cited by 80 · see citing works
Self-citationAthanasopoulos, T., Graham, I., Foster, H., & Dickson, G. (2004) · Gene Therapy · doi:10.1038/sj.gt.3302379 · Cited by 68 · see citing works
Can Adeno-Associated Viral Vectors Deliver Effectively Large Genes?
Tornabene, P., & Trapani, I. (2020) · Human Gene Therapy · doi:10.1089/hum.2019.220 · Cited by 76 · see citing works
Emerging strategies for cell and gene therapy of the muscular dystrophies
Muir, L. A., & Chamberlain, J. (2009) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399409001100 · Cited by 77 · 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
Efficient Whole-body Transduction with Trans-splicing Adeno-associated Viral Vectors.
Ghosh, A., Yue, Y., Long, C., Bostick, B., & Duan, D. (2007) · Molecular Therapy · doi:10.1038/sj.mt.6300153 · Cited by 53 · see citing works
Self-citationLópez-Bueno, A., Mateu, M. G., & Almendral, J. M. (2003) · Journal of Virology · doi:10.1128/jvi.77.4.2701-2708.2003 · Cited by 73 · see citing works
Endothelium-Targeted Gene and Cell-Based Therapies for Cardiovascular Disease
Melo, L. G., Gnecchi, M., Pachori, A. S., Kong, D., Wang, K., Liu, X., Pratt, R. E., & Dzau, V. J. (2004) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000142363.15113.88 · Cited by 72 · see citing works
The next step in gene delivery: Molecular engineering of adeno-associated virus serotypes
Wang, J., Faust, S. M., & Rabinowitz, J. E. (2010) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2010.10.017 · Cited by 69 · see citing works
Current Status of Gene Therapy for Inherited Lung Diseases
Driskell, R. R., & Engelhardt, J. F. (2003) · Annual Review of Physiology · doi:10.1146/annurev.physiol.65.092101.142426 · Cited by 69 · see citing works
Self-citationGhosh, A., Yue, Y., & Duan, D. (2006) · The Journal of Gene Medicine · doi:10.1002/jgm.835 · Cited by 69 · see citing works
Self-citationZou, W., Cheng, F., Shen, W., Engelhardt, J. F., Yan, Z., & Qiu, J. (2016) · Journal of Virology · doi:10.1128/jvi.02964-15 · Cited by 68 · see citing works
Self-citationRecruitment of Transcription Complexes to the β-Globin Gene Locus in Vivo and in Vitro
Vieira, K. F., Levings, P. P., Hill, M. A., Crusselle‐Davis, V. J., Kang, S.-H. L., Engel, J. D., & Bungert, J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m408883200 · Cited by 68 · see citing works
Scallan, C. D., Liu, T., Parker, A. E., Patarroyo-White, S. L., Chen, H., Jiang, H., Vargas, J. A., Nagy, D., Powell, S. K., Wright, J. F., et al. (2003) · Blood · doi:10.1182/blood-2003-01-0222 · Cited by 68 · see citing works
Adeno-Associated Virus Genome Interactions Important for Vector Production and Transduction
Maurer, A. C., & Weitzman, M. D. (2020) · Human Gene Therapy · doi:10.1089/hum.2020.069 · Cited by 65 · see citing works
Adriaansen, J., Vervoordeldonk, M. J., & Tak, P. P. (2006) · Rheumatology · doi:10.1093/rheumatology/kel047 · Cited by 65 · see citing works
New developments in the use of gene therapy to treat Duchenne muscular dystrophy
Jarmin, S., Kymäläinen, H., Popplewell, L. J., & Dickson, G. (2013) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2014.866087 · Cited by 65 · see citing works
Suppression of Choroidal Neovascularization by AAV-Based Dual-Acting Antiangiogenic Gene Therapy
Askou, A. L., Alsing, S., Benckendorff, J. N. E., Holmgaard, A., Mikkelsen, J. G., Aagaard, L., Bek, T., & Corydon, T. J. (2019) · Molecular Therapy - Nucleic Acids · doi:10.1016/j.omtn.2019.01.012 · Cited by 64 · see citing works
Design of AAV Vectors for Delivery of Large or Multiple Transgenes
Patel, A., Zhao, J., Duan, D., & Lai, Y. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9139-6_2 · Cited by 64 · see citing works
Self-citationEfficient whole-body transduction with trans-splicing adeno-associated viral vectors.
Ghosh, A., Yue, Y., Long, C., Bostick, B., & Duan, D. (2007) · Molecular Therapy · doi:10.1038/sj.mt.6300081 · Cited by 41 · see citing works
Self-citationSong, Y., Lou, H. H., Boyer, J. L., Limberis, M. P., Vandenberghe, L. H., Hackett, N. R., Leopold, P. L., Wilson, J. M., & Crystal, R. G. (2009) · Human Gene Therapy · doi:10.1089/hum.2008.173 · Cited by 61 · see citing works
Effects of Adeno-Associated Virus DNA Hairpin Structure on Recombination
Choi, V., Samulski, R., & Mccarty, D. (2005) · Journal of Virology · doi:10.1128/jvi.79.11.6801-6807.2005 · Cited by 55 · see citing works
Sanlioglu, S., Duan, D.-S., & Engelhardt, J. F. (1999) · Human Gene Therapy · doi:10.1089/10430349950018661 · Cited by 70 · see citing works
Self-citationParvovirus Variation for Disease: A Difference with RNA Viruses?
López-Bueno, A., Villarreal, L. P., & Almendral, J. M. (2006) · Current topics in microbiology and immunology · doi:10.1007/3-540-26397-7_13 · Cited by 56 · see citing works
Xu, Z., Yue, Y., Lai, Y., Ye, C., Qiu, J., Pintel, D. J., & Duan, D. (2004) · Human Gene Therapy · doi:10.1089/hum.2004.15.896 · Cited by 55 · see citing works
Self-citationA User's Guide to the Inverted Terminal Repeats of Adeno-Associated Virus
Wilmott, P., Lisowski, L., Alexander, I. E., & Logan, G. J. (2019) · Human Gene Therapy Methods · doi:10.1089/hgtb.2019.276 · Cited by 54 · see citing works
Stargardt disease and progress in therapeutic strategies
Huang, D., Jeffery, R. C. H., Aung-Htut, M. T., McLenachan, S., Fletcher, S., Wilton, S. D., & Chen, F. K. (2021) · Ophthalmic Genetics · doi:10.1080/13816810.2021.1966053 · Cited by 56 · see citing works
Preclinical evaluation of the efficacy and safety of AAV1-hOTOF in mice and nonhuman primates
Zhang, L., Wang, H., Xun, M., Tang, H., Wang, J., Lv, J., Zhu, B., Chen, Y., Wang, D., Hu, S., et al. (2023) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2023.101154 · Cited by 55 · see citing works
Duan, D., Yue, Y., & Engelhardt, J. (2003) · Journal of Virology · doi:10.1128/jvi.77.8.4751-4759.2003 · Cited by 63 · see citing works
Self-citationHirano, M., Kato, S., Kobayashi, K., Okada, T., Yaginuma, H., & Kobayashi, K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0075896 · Cited by 54 · see citing works
Sarkar, R., Xiao, W., & Kazazian, H. H. (2003) · Journal of Thrombosis and Haemostasis · doi:10.1046/j.1538-7836.2003.00096.x · Cited by 54 · see citing works
Sustainable Systemic Delivery via a Single Injection of Lentivirus into Human Skin Tissue
Baek, S., Lin, Q., Robbins, P. B., Fan, H., & Khavari, P. A. (2001) · Human Gene Therapy · doi:10.1089/10430340152480276 · Cited by 54 · see citing works
Expanding Adeno-associated Viral Vector Capacity: A Tale of Two Vectors
Ghosh, A., & Duan, D. (2007) · Biotechnology & Genetic Engineering Reviews · doi:10.1080/02648725.2007.10648098 · Cited by 57 · see citing works
Self-citationPryadkina, M., Lostal, W., Bourg, N., Charton, K., Roudaut, C., Hirsch, M. L., & Richard, I. (2015) · Molecular Therapy - Methods & Clinical Development · doi:10.1038/mtm.2015.9 · Cited by 53 · see citing works
Beier, K. T., Saunders, A. B., Oldenburg, I. A., Sabatini, B. L., & Cepko, C. L. (2013) · Frontiers in Neural Circuits · doi:10.3389/fncir.2013.00011 · Cited by 52 · see citing works
Controlled release strategies for rAAV-mediated gene delivery
Rey‐Rico, A., & Cucchiarini, M. (2015) · Acta Biomaterialia · doi:10.1016/j.actbio.2015.10.015 · Cited by 52 · see citing works
Burdett, T., & Nuseibeh, S. (2022) · Gene Therapy · doi:10.1038/s41434-022-00363-0 · Cited by 51 · see citing works
- Authors
- Yan, Z., Zhang, Y., Duan, D., & Engelhardt, J. F.
- Affiliations
- University of Iowa (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2000-06-06
- Volume
- 97
- Issue
- 12
- Pages
- 6716-6721
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC18714
- OpenAlex
- W2082328650
- Cited by
- 305
- References
- 20
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 9 · 2023: 10 · 2022: 5 · 2021: 12 · 2020: 12 · 2019: 14 · 2018: 9 · 2017: 10 · 2016: 7 · 2015: 11 · 2014: 9 · 2013: 14 · 2012: 7
- FWCI
- 13.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL058340, R01 HL58340)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK 54759, P30DK054759)
- 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
- Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
- Keywords
- adeno-associated virus vectors, trans-splicing, erythropoietin, gene therapy
- MeSH terms
- Dependovirus, Anemia, Animals, Erythropoietin, Genetic Vectors, Kidney Failure, Chronic, Mice, Inbred C57BL, Muscles, Genetic Therapy, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
