Adeno-Associated Virus Integration: Virus versus Vector
Abstract
Although a large percentage of the world population is seropositive for exposure to various strains of adeno-associated virus (AAV), a human parvovirus, AAV has never been identified as an etiologic agent of human disease. Most likely contributing to the pronounced lack of pathogenicity is the fact that AAV is a naturally defective virus that requires a helper virus for productive replication of its genome. Another unusual aspect of wild-type AAV biology is the ability of the virus to establish latent infection by preferential integration of its genome into a specific locus of human chromosome 19. Site-specific integration was a major impetus for the development of recombinant AAV vectors, which typically lack all AAV coding sequences. It was soon realized, however, that expression of at least one species of the virally encoded initiator proteins, Rep78 or Rep68, is necessary for targeted integration of AAV-derived DNA constructs to occur. This article will present a chronological outline of studies characterizing site-specific integration of wild-type AAV sequences and the quasi-random target site selection observed with recombinant AAV vectors.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Recombinant AAV rarely integrates into the host cell genome, reducing the risk of insertional mutagenesis following gene therapy.
“Furthermore, recombinant AAV (rAAV) rarely integrates into the host cell genome, thereby reducing the risk of insertional mutagenesis following gene therapy [44].”
From Immune responses to gene editing by viral and non-viral delivery vectors used in retinal gene therapy (2022) · cites this paper as [44]
Cites
Adenovirus-Associated Defective Virus Particles
Atchison, R. W., Casto, B. C., & Hammon, W. M. (1965) · Science · doi:10.1126/science.149.3685.754 · Cited by 1,004 · see citing works
Site-specific integration by adeno-associated virus.
Kotin, R. M., Siniscalco, M., Samulski, R. J., Zhu, X. D., Hunter, L., Laughlin, C. A., McLaughlin, S., Muzyczka, N., Rocchi, M., & Berns, K. I. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.6.2211 · Cited by 906 · see citing works
Site-specific integration by adeno-associated virus.
Linden, R. M., Ward, P., Giraud, C., Winocour, E., & Berns, K. I. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.21.11288 · Cited by 805 · see citing works
Targeted integration of adeno‐associated virus (AAV) into human chromosome 19.
Samulski, R. J., Zhu, X., Xiao, X., Brook, J. D., Housman, D. E., Epstein, N., & Hunter, L. A. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb04964.x · Cited by 783 · see citing works
Recombinant adeno-associated virus for muscle directed gene therapy
Fisher, K. J., Jooss, K., Alston, J., Yang, Y., Haecker, S. E., High, K., Pathak, R., Raper, S. E., & Wilson, J. M. (1997) · Nature Medicine · doi:10.1038/nm0397-306 · Cited by 654 · see citing works
Kotin, R. M., Linden, R. M., & Berns, K. I. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05614.x · Cited by 513 · see citing works
Nakai, H., Yant, S. R., Storm, T. A., Fuess, S., Meuse, L., & Kay, M. A. (2001) · Journal of Virology · doi:10.1128/jvi.75.15.6969-6976.2001 · Cited by 478 · see citing works
Im, D., & Muzyczka, N. (1990) · Cell · doi:10.1016/0092-8674(90)90526-k · Cited by 466 · see citing works
AAV serotype 2 vectors preferentially integrate into active genes in mice
Nakai, H., Montini, E., Fuess, S., Storm, T. A., Grompe, M., & Kay, M. A. (2003) · Nature Genetics · doi:10.1038/ng1179 · Cited by 392 · see citing works
Weitzman, M. D., Kyöstió, S. R., Kotin, R. M., & Owens, R. A. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.13.5808 · Cited by 379 · see citing works
Thomas, C. E., Storm, T. A., Huang, Z., & Kay, M. A. (2004) · Journal of Virology · doi:10.1128/jvi.78.6.3110-3122.2004 · Cited by 358 · see citing works
Cheung, A. K., HOGGAN, M. D., Hauswirth, W. W., & Berns, K. I. (1980) · Journal of Virology · doi:10.1128/jvi.33.2.739-748.1980 · Cited by 287 · see citing works
Adeno-associated virus Rep proteins target DNA sequences to a unique locus in the human genome
Surosky, R. T., Urabe, M., Godwin, S. G., McQuiston, S. A., Kurtzman, G. J., OZAWA, K., & Natsoulis, G. (1997) · Journal of Virology · doi:10.1128/jvi.71.10.7951-7959.1997 · Cited by 244 · see citing works
Smith-Arica, J. R., Maguire, S. F., Davis, L. A., Alexander, M., Yang, F., Chandran, S., ffrench‐Constant, C., & Pedersen, R. A. (2007) · Stem Cells · doi:10.1634/stemcells.2007-0039 · Cited by 241 · see citing works
The recombination signals for adeno-associated virus site-specific integration.
Linden, R. M., Winocour, E., & Berns, K. I. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.15.7966 · Cited by 241 · see citing works
The kinetics of rAAV integration in the liver
Miao, C. H., Snyder, R., Schowalter, D., Patijn, G., Donahue, B., Winther, B. L., & Kay, M. (1998) · Nature Genetics · doi:10.1038/ng0598-13 · Cited by 198 · see citing works
Kearns, W. G., Afione, S. A., Fulmer, S. B., Pang, M. C., Erikson, D., Egan, M. E., Landrum, M., Flotte, T. R., & Cutting, G. R. (1996) · PubMed · Cited by 191 · see citing works
Large‐scale molecular characterization of adeno‐associated virus vector integration in mouse liver
Nakai, H., Wu, X., Fuess, S., Storm, T. A., Munroe, D., Montini, E., Burgess, S. M., Grompe, M., & Kay, M. A. (2005) · Journal of Virology · doi:10.1128/jvi.79.6.3606-3614.2005 · Cited by 190 · see citing works
Isolation of Recombinant Adeno-Associated Virus Vector-Cellular DNA Junctions from Mouse Liver
Nakai, H., Iwaki, Y., Kay, M. A., & Couto, L. B. (1999) · Journal of Virology · doi:10.1128/jvi.73.7.5438-5447.1999 · Cited by 186 · see citing works
Large-Scale Analysis of Adeno-Associated Virus Vector Integration Sites in Normal Human Cells
Miller, D. G., Trobridge, G. D., Petek, L. M., Jacobs, M. A., Kaul, R., & Russell, D. W. (2005) · Journal of Virology · doi:10.1128/jvi.79.17.11434-11442.2005 · Cited by 171 · see citing works
Site-specific integration by adeno-associated virus is directed by a cellular DNA sequence.
Giraud, C., Winocour, E., & Berns, K. I. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.21.10039 · Cited by 149 · see citing works
Berns, K. I., Pinkerton, T. C., Thomas, G., & HOGGAN, M. D. (1975) · Virology · doi:10.1016/0042-6822(75)90298-6 · Cited by 147 · see citing works
Balagué, C., Kalla, M., & Zhang, W. (1997) · Journal of Virology · doi:10.1128/jvi.71.4.3299-3306.1997 · Cited by 147 · see citing works
Urcelay, E., Ward, P., Wiener, S. M., Safer, B., & Kotin, R. M. (1995) · Journal of Virology · doi:10.1128/jvi.69.4.2038-2046.1995 · Cited by 131 · see citing works
Organization of adeno-associated virus DNA in latently infected detroit 6 cells
Kotin, R. M., & Berns, K. I. (1989) · Virology · doi:10.1016/0042-6822(89)90437-6 · Cited by 128 · see citing works
Identification of a DNA-binding domain in the amino terminus of adeno-associated virus Rep proteins
Owens, R. A., Weitzman, M. D., Kyöstió, S. R., & Carter, B. J. (1993) · Journal of Virology · doi:10.1128/jvi.67.2.997-1005.1993 · Cited by 107 · see citing works
Hauck, B., Zhao, W., High, K. A., & Xiao, W. (2004) · Journal of Virology · doi:10.1128/jvi.78.24.13678-13686.2004 · Cited by 98 · see citing works
Ogata, T., Kozuka, T., & Kanda, T. (2003) · Journal of Virology · doi:10.1128/jvi.77.16.9000-9007.2003 · Cited by 73 · see citing works
Lamartina, S., Sporeno, E., Fattori, E., & Toniatti, C. (2000) · Journal of Virology · doi:10.1128/jvi.74.16.7671-7677.2000 · Cited by 49 · see citing works
Gonçalves, M. A. F. V., van Nierop, G. P., Tijssen, M. R., Lefesvre, P., Knaän‐Shanzer, S., van der Velde, I., van Bekkum, D. W., Valerio, D., & de Vries, A. A. F. (2005) · Journal of Virology · doi:10.1128/jvi.79.5.3146-3162.2005 · Cited by 46 · see citing works
Cortés, M. L., Oehmig, A., Saydam, O., Sanford, J. D., Perry, K. F., Fraefel, C., & Breakefield, X. O. (2008) · Molecular Therapy · doi:10.1038/sj.mt.6300338 · Cited by 37 · see citing works
Wang, H., & Lieber, A. (2006) · Journal of Virology · doi:10.1128/jvi.00779-06 · Cited by 37 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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 · see citing works
Lee, C. S., Bishop, E. S., Zhang, R., Yu, X., Farina, E. M., Yan, S., Zhao, C., Zeng, Z., Shu, Y., Wu, X., et al. (2017) · Genes & Diseases · doi:10.1016/j.gendis.2017.04.001 · Cited by 691 · see citing works
Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas
Nault, J.-C., Datta, S., Imbeaud, S., Franconi, A., Mallet, M., Couchy, G., Letouzé, E., Pilati, C., Verret, B., Blanc, J.-F., et al. (2015) · Nature Genetics · doi:10.1038/ng.3389 · Cited by 489 · see citing works
Human Immune Responses to Adeno-Associated Virus (AAV) Vectors
Ronzitti, G., Gross, D.-A., & Mingozzi, F. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00670 · Cited by 357 · see citing works
Genetic profiling of hepatocellular carcinoma using next-generation sequencing
Schulze, K., Nault, J., & Villanueva, A. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.05.035 · Cited by 318 · see citing works
(2013) · PubMed · Cited by 308 · see citing works
Polymeric Materials for Gene Delivery and DNA Vaccination
Nguyen, D. N., Green, J. J., Chan, J. M., Langer, R., & Anderson, D. G. (2008) · Advanced Materials · doi:10.1002/adma.200801478 · Cited by 273 · see citing works
Virus-mediated gene delivery for human gene therapy
Giacca, M., & Zacchigna, S. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.04.008 · Cited by 302 · see citing works
Bucher, K., Rodríguez-Bocanegra, E., Dauletbekov, D., & Fischer, M. D. (2021) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100915 · Cited by 242 · 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
Jüttner, J., Szabo, A., Gross-Scherf, B., Morikawa, R. K., Rompani, S. B., Hantz, P., Szikra, T., Esposti, F., Cowan, C. S., Bharioke, A., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0431-2 · Cited by 218 · see citing works
Advances in Gene Delivery Systems
Kamimura, K., Suda, T., Zhang, G., & Liu, D. (2011) · Pharmaceutical Medicine · doi:10.1007/bf03256872 · Cited by 211 · see citing works
Genomes in conflict: maintaining genome integrity during virus infection.
Weitzman, M., Lilley, C., & Chaurushiya, M. S. (2010) · Annual Review of Microbiology · doi:10.1146/annurev.micro.112408.134016 · Cited by 201 · see citing works
Adeno-associated viral vector-mediated immune responses: Understanding barriers to gene delivery
Nidetz, N. F., McGee, M. C., Tse, L. V., Li, C., Cong, L., Li, Y., & Huang, W. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.107453 · Cited by 174 · see citing works
“While the WT AAV genome integrates into the host genome after transduction, recombinant AAV transgenes have conversely been shown to remain episomal in transduced cells (Grieger & Samulski, 2012; Smith, 2008; Valdmanis, et al., 2012).”
BackgroundSaunders, A. B., Johnson, C. A., & Sabatini, B. L. (2012) · Frontiers in Neural Circuits · doi:10.3389/fncir.2012.00047 · Cited by 165 · see citing works
Targeting microglia with lentivirus and AAV: Recent advances and remaining challenges
Maes, M. E., Colombo, G., Schulz, R., & Siegert, S. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.134310 · Cited by 145 · see citing works
Durability of transgene expression after rAAV gene therapy
Muhuri, M., Lévy, D., Schulz, M., McCarty, D. M., & Gao, G. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.03.004 · Cited by 148 · see citing works
Adeno-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 · 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
Schulz, M., Lévy, D., Petropoulos, C. J., Bashirians, G., Winburn, I. C., Mahn, M., Somanathan, S., Cheng, S. H., & Byrne, B. J. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2023.01.010 · Cited by 132 · see citing works
Targeting T cell malignancies using CAR-based immunotherapy: challenges and potential solutions
Fleischer, L. C., Spencer, H. T., & Raikar, S. S. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0801-y · Cited by 126 · see citing works
Viral manipulation of DNA repair and cell cycle checkpoints
Chaurushiya, M. S., & Weitzman, M. D. (2009) · DNA repair · doi:10.1016/j.dnarep.2009.04.016 · Cited by 120 · see citing works
Adeno-associated viral vectors do not efficiently target muscle satellite cells
Arnett, A. L. H., Konieczny, P., Ramos, J., Hall, J. K., Odom, G., Yablonka-Reuveni, Z., Chamberlain, J. R., & Chamberlain, J. (2014) · Molecular Therapy: Methods & Clinical Development · doi:10.1038/mtm.2014.38 · Cited by 82 · see citing works
Methods for Gene Transfer to the Central Nervous System
Kantor, B., Bailey, R. M., Wimberly, K., Kalburgi, S. N., & Gray, S. J. (2014) · Advances in Genetics · doi:10.1016/b978-0-12-800149-3.00003-2 · Cited by 109 · see citing works
Development of hybrid viral vectors for gene therapy
Huang, S., & Kamihira, M. (2012) · Biotechnology Advances · doi:10.1016/j.biotechadv.2012.10.001 · Cited by 99 · see citing works
Li, X., Salvia, S. L., Liang, Y., Adamiak, M., Kohlbrenner, E., Jeong, D., Chepurko, E., Ceholski, D. K., López-Gordo, E., Yoon, S., et al. (2023) · Circulation · doi:10.1161/circulationaha.122.063759 · Cited by 91 · see citing works
Delbeke, J., Hoffman, L., Mols, K., Braeken, D., & Prodanov, D. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00663 · Cited by 87 · see citing works
Monahan, P. E., Négrier, C., Tarantino, M. D., Valentino, L. A., & Mingozzi, F. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10112471 · Cited by 85 · see citing works
The Different Faces of Rolling-Circle Replication and Its Multifunctional Initiator Proteins
Wawrzyniak, P., Płucienniczak, G., & Bartosik, D. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.02353 · Cited by 84 · see citing works
Engineering Gene Therapy: Advances and Barriers
Shahryari, A., Burtscher, I., Nazari, Z., & Lickert, H. (2021) · Advanced Therapeutics · doi:10.1002/adtp.202100040 · Cited by 84 · see citing works
Single‐stranded DNA viruses employ a variety of mechanisms for integration into host genomes
Krupovìč, M., & Forterre, P. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12675 · Cited by 76 · see citing works
Non-Integrating Lentiviral Vectors
Sarkis, C., Philippe, S., Mallet, J. J., & Serguera, C. (2008) · Current Gene Therapy · doi:10.2174/156652308786848012 · Cited by 74 · see citing works
tRNA therapeutics for genetic diseases
Coller, J., & Ignatova, Z. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00829-9 · Cited by 72 · see citing works
Cystic fibrosis: Exploiting its genetic basis in the hunt for new therapies
Kreindler, J. L. (2009) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2009.10.006 · Cited by 67 · see citing works
Torres‐Torronteras, J., Viscomi, C. F., Cabrera-Pérez, R., Cámara, Y., Meo, I. D., Barquinero, J., Auricchio, A., Pizzorno, G., Hirano, M., Zeviani, M., et al. (2014) · Molecular Therapy · doi:10.1038/mt.2014.6 · Cited by 65 · see citing works
Gross, D., Tedesco, N., Leborgne, C., & Ronzitti, G. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.857276 · Cited by 63 · see citing works
Locating and labeling neural stem cells in the brain
Landgren, H., & Curtis, M. A. (2010) · Journal of Cellular Physiology · doi:10.1002/jcp.22319 · Cited by 63 · see citing works
Strecker, M. I., Wlotzka, K., Straßheimer, F., Roller, B., Ludmirski, G., König, S., Röder, J., Opitz, C., Alekseeva, T., Reul, J., et al. (2022) · OncoImmunology · doi:10.1080/2162402x.2022.2127508 · Cited by 60 · see citing works
Advancements in the design and scalable production of viral gene transfer vectors
Sharon, D., & Kamen, A. (2018) · Biotechnology and Bioengineering · doi:10.1002/bit.26461 · Cited by 51 · see citing works
AAV for Gene Therapy in Ocular Diseases: Progress and Prospects
He, X., Fu, Y., Ma, L., Yao, Y., Ge, S., Yang, Z. H., & Fan, X. (2023) · Research · doi:10.34133/research.0291 · Cited by 59 · see citing works
Targeted in vivo knock-in of human alpha-1-antitrypsin cDNA using adenoviral delivery of CRISPR/Cas9
Stephens, C. J., Kashentseva, E. A., Everett, W., Kaliberova, L. N., & Curiel, D. T. (2018) · Gene Therapy · doi:10.1038/s41434-018-0003-1 · Cited by 57 · see citing works
Rittiner, J. E., Moncalvo, M., Chiba‐Falek, O., & Kantor, B. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00148 · Cited by 51 · see citing works
Ren, D., Fisson, S., Dalkara, D., & Ail, D. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14091973 · Cited by 52 · see citing works
Non-Retroviral Fossils in Vertebrate Genomes
Horie, M., & Tomonaga, K. (2011) · Viruses · doi:10.3390/v3101836 · Cited by 51 · see citing works
Progress and challenges of gene therapy for Pompe disease
Ronzitti, G., Collaud, F., Laforêt, P., & Mingozzi, F. (2019) · Annals of Translational Medicine · doi:10.21037/atm.2019.04.67 · Cited by 52 · see citing works
Viral and Transgenic Reporters and Genetic Analysis of Adult NeurogenesisPreprint
Enikolopov, G., Overstreet‐Wadiche, L., & Ge, S. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a018804 · Cited by 51 · see citing works
Gene Therapy Developments for Pompe Disease
Unnisa, Z., Yoon, J. K., Schindler, J. W., Mason, C., & van Til, N. P. (2022) · Biomedicines · doi:10.3390/biomedicines10020302 · Cited by 52 · see citing works
Hippert, C., Ibanes, S., Serratrice, N., Court, F., Malecaze, F., Kremer, E. J., & Kalatzis, V. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035318 · Cited by 47 · see citing works
AAV for pain: steps towards clinical translation
Beutler, A. S., & Reinhardt, M. (2009) · Gene Therapy · doi:10.1038/gt.2009.23 · Cited by 44 · see citing works
Targeting adeno-associated virus and adenoviral gene therapy for hepatocellular carcinoma
Wang, Y. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i1.326 · Cited by 41 · see citing works
Viral vector approaches to modify gene expression in the brain
Papale, A., Cerovic, M., & Brambilla, R. (2009) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2009.08.013 · Cited by 39 · see citing works
Gene Therapy for Mucopolysaccharidosis Type II—A Review of the Current Possibilities
Zapolnik, P., & Pyrkosz, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115490 · Cited by 39 · see citing works
Rittiner, J. E., Cumaran, M., Malhotra, S., & Kantor, B. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.1035543 · Cited by 40 · see citing works
Approaches to gene modulation therapy for ALS
Meijboom, K. E., & Brown, R. H. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01285-w · Cited by 38 · see citing works
Updates on current advances in gene therapy.
Tani, J., Faustine, & Sufian, J. T. (2011) · PubMed · Cited by 37 · see citing works
van Nierop, G. P., de Vries, A. A. F., Holkers, M., Vrijsen, K. R., & Gonçalves, M. A. F. V. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp643 · Cited by 37 · 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
He, S., Li, Z., Xie, L., Lin, R., Yan, B., Li, B., Luo, L., Xv, Y., Wen, H., Liang, Y., et al. (2025) · Journal of Nanobiotechnology · doi:10.1186/s12951-025-03261-w · Cited by 32 · see citing works
Kantor, B., O’Donovan, B., & Chiba‐Falek, O. (2025) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2025.102635 · Cited by 36 · see citing works
Riedel, M. J., Gaddy, D. F., Asadi, A., Robbins, P. D., & Kieffer, T. J. (2009) · Gene Therapy · doi:10.1038/gt.2009.143 · Cited by 31 · see citing works
Gene Transfer Therapy for Neurodevelopmental Disorders
Özlü, C., Bailey, R. M., Sinnett, S. E., & Goodspeed, K. (2021) · Developmental Neuroscience · doi:10.1159/000515434 · Cited by 31 · see citing works
Zdechlik, A. C., He, Y., Aird, E. J., Gordon, W. R., & Schmidt, D. (2019) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.9b00790 · Cited by 28 · see citing works
Ussher, J. E., & Taylor, J. A. (2010) · Human Gene Therapy · doi:10.1089/hum.2010.087 · Cited by 29 · see citing works
Shoop, W. K., Bacman, S. R., Barrera-Paez, J. D., & Moraes, C. T. (2023) · Nature Reviews Methods Primers · doi:10.1038/s43586-023-00200-7 · Cited by 33 · see citing works
Recombinant AAV-directed gene therapy for type I glycogen storage diseases
CHOU, J. Y., & Mansfield, B. C. (2011) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2011.578067 · Cited by 27 · see citing works
Grinshpun, A., Condiotti, R., Waddington, S. N., Peer, M., Zeig, E., Peretz, S., Simerzin, A., CHOU, J. Y., Pan, C., Giladi, H., et al. (2010) · Molecular Therapy · doi:10.1038/mt.2010.119 · Cited by 26 · see citing works
Systemic administration of AAV-Slc25a46 mitigates mitochondrial neuropathy in Slc25a46−/− mice
Yang, L., Slone, J. D., Li, Z., Lou, X., Hu, Y., Queme, L. F., Jankowski, M. P., & Huang, T. (2020) · Human Molecular Genetics · doi:10.1093/hmg/ddz277 · Cited by 26 · see citing works
Vectors for pulmonary gene therapy
Geiger, J. P., Aneja, M. K., & Rudolph, C. (2009) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2009.10.010 · Cited by 25 · see citing works
Jackson, R., Togtema, M., Lambert, P. F., & Zehbe, I. (2014) · PLoS ONE · doi:10.1371/journal.pone.0101540 · Cited by 24 · see citing works
Ex Vivo Gene Therapy and Vision
Gregory-Evans, K., Bashar, E., & Tan, M. (2012) · Current Gene Therapy · doi:10.2174/156652312800099607 · Cited by 23 · see citing works
AAV-mediated gene therapy for galactosialidosis: A long-term safety and efficacy study
Hu, H., Mosca, R., Gomero, E. M., van de Vlekkert, D., Campos, Y., Fremuth, L. E., Brown, S. A., Weesner, J. A., Annunziata, I., & d’Azzo, A. (2021) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2021.10.007 · Cited by 22 · see citing works
Human artificial chromosomes for Duchenne muscular dystrophy and beyond: challenges and hopes
Tedesco, F. S. (2015) · Chromosome Research · doi:10.1007/s10577-014-9460-6 · Cited by 21 · see citing works
Gonçalves, M. A. F. V., Holkers, M., van Nierop, G. P., Wieringa, R., Pau, M. G., & de Vries, A. A. F. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003084 · Cited by 21 · see citing works
Silva-Pilipich, N., Smerdou, C., & Vanrell, L. (2021) · Microorganisms · doi:10.3390/microorganisms9091956 · Cited by 21 · see citing works
Prospects for genetic modulation of corneal graft survival
Williams, K. A., Brereton, H. M., & Coster, D. J. (2008) · Eye · doi:10.1038/eye.2008.378 · Cited by 21 · see citing works
Xu, M., Leskinen, K., Gritti, T., Groma, V., Arola, J. T., Lepistö, A., Sipponen, T. M., Saavalainen, P., & Söderlund‐Venermo, M. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.914181 · Cited by 20 · see citing works
Hall, M. S., Decker, J. T., & Shea, L. D. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.120189 · Cited by 20 · see citing works
Geiling, B., Vandal, G., Posner, A., de Bruyns, A., Dutchak, K., Garnett, S., & Dankort, D. L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0076279 · Cited by 19 · see citing works
Prea, S. M., Chan, E. C., Dusting, G. J., Vingrys, A. J., Bui, B. V., & Liu, G. (2015) · Journal of Ophthalmology · doi:10.1155/2015/201726 · Cited by 20 · see citing works
Virally mediated gene manipulation in the adult CNS
Edry, E., Lamprecht, R., Wagner, S., & Rosenblum, K. (2011) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2011.00057 · Cited by 18 · see citing works
Han, Q., Xiang, J., Zhang, Y., Qiao, H., YongWei, S., & Zhang, C. (2014) · Chinese Medical Journal · doi:10.3760/cma.j.issn.0366-6999.20141717 · Cited by 18 · see citing works
Adeno-Associated Viral Gene Delivery in Neurodegenerative Disease
Morgenstern, P. F., Marongiu, R., Musatov, S. A., & Kaplitt, M. G. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-328-8_29 · Cited by 19 · see citing works
Genomics of Viral Hepatitis-Associated Liver Tumors
Péneau, C., Zucman-Rossi, J., & Nault, J. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10091827 · Cited by 17 · see citing works
Genetic vaccination for re-establishing T-cell tolerance in type 1 diabetes
Johnson, M. C., Wang, B., & Tisch, R. (2011) · Human Vaccines · doi:10.4161/hv.7.1.12848 · Cited by 18 · see citing works
Advances in viral vector-based delivery systems for gene therapy: a comprehensive review
Singh, K., Jain, D., Sethi, P., Gupta, J. K., Dubey, A., Noman, A. A., lal, S., Sharma, P., & Abdallah, E. M. (2025) · 3 Biotech · doi:10.1007/s13205-025-04366-7 · Cited by 19 · see citing works
Eisenman, D., & Swindle, S. (2022) · Applied biosafety : journal of the American Biological Safety Association · doi:10.1089/apb.2022.0022 · Cited by 17 · see citing works
Hoad, M., Cross, E. M., Donnelly, C. M., Sarker, S., Roby, J. A., & Forwood, J. K. (2023) · Viruses · doi:10.3390/v15020315 · Cited by 17 · see citing works
Use of gene therapy for optic nerve protection: Current concepts
Xu, K., Yu, L., Wang, Z., Lin, P., Zhang, N., Xing, Y., & Yang, N. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1158030 · Cited by 17 · see citing works
Singh, M., Brööks, A. G., Toofan, P., & McLuckie, K. (2023) · Gene Therapy · doi:10.1038/s41434-023-00417-x · Cited by 15 · see citing works
Gene Therapy - Developments and Future Perspectives
Kang, C. (2011) · InTech eBooks · doi:10.5772/748 · Cited by 16 · see citing works
Urich, J., Cucchiarini, M., & Rey‐Rico, A. (2020) · Nanomaterials · doi:10.3390/nano10061238 · Cited by 16 · see citing works
Context-Specific Function of the Engineered Peptide Domain of PHP.B
Martino, R. A., Fluck, E. C., Murphy, J., Wang, Q., Hoff, H. B., Pumroy, R. A., Lee, C. Y., Sims, J. J., Roy, S., Moiseenkova‐Bell, V. Y., et al. (2021) · Journal of Virology · doi:10.1128/jvi.01164-21 · Cited by 16 · see citing works
An ex vivo gene therapy approach in X-linked retinoschisis.
Bashar, E., Metcalfe, A. L., viringipurampeer, I. A., Yanai, A., Gregory, C. Y., & Gregory-Evans, K. (2016) · PubMed Central · Cited by 16 · see citing works
Stolte, B., Schreiber-Katz, O., Günther, R., Wurster, C. D., Petri, S., Osmanovic, A., Freigang, M., Uzelac, Z., Leo, M., von Velsen, O., et al. (2022) · Human Gene Therapy · doi:10.1089/hum.2022.054 · Cited by 15 · see citing works
Day, J., Mendell, J. R., Burghes, A. H. M., van Olden, R. W., Adhikary, R. R., & Dilly, K. W. (2023) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2023.101117 · Cited by 14 · see citing works
A Simple, Two-Step, Small-Scale Purification of Recombinant Adeno-Associated Viruses
Chen, S., Papaneri, A. B., Walker, M., Scappini, E., Keys, R. D., & Martin, N. P. (2020) · Journal of Virological Methods · doi:10.1016/j.jviromet.2020.113863 · Cited by 14 · see citing works
High-efficiency knock-in of degradable tags (dTAG) at endogenous loci in cell lines
Mehta, S., Buyanbat, A., Orkin, S. H., & Nabet, B. (2022) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2022.08.045 · Cited by 13 · see citing works
Multidimensional Genome-wide Analyses Show Accurate FVIII Integration by ZFN in Primary Human Cells
Sivalingam, J., Kenanov, D., Han, H., Nirmal, A. J., Ng, W. H., Lee, S. S., Masilamani, J., Phan, T. T., Maurer‐Stroh, S., & Kon, O. L. (2015) · Molecular Therapy · doi:10.1038/mt.2015.223 · Cited by 13 · see citing works
Binny, C., & Nathwani, A. C. (2012) · Humana Press eBooks · doi:10.1007/978-1-61779-873-3_6 · Cited by 12 · see citing works
Huang, S., Kawabe, Y., Itô, A., & Kamihira, M. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.11.059 · Cited by 11 · see citing works
- Authors
- Smith, R. H.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Smith, R H
- ORCID
- Smith, R H
- Venue
- Gene Therapy
- Published
- 2008-04-10
- Volume
- 15
- Issue
- 11
- Pages
- 817-822
- ISSN
- 0969-7128 (ISSN-L)
- 1476-5462
- OpenAlex
- W2034226542
- Cited by
- 178
- References
- 32
- Citations by year
- 2026: 1 · 2025: 11 · 2024: 8 · 2023: 11 · 2022: 16 · 2021: 12 · 2020: 11 · 2019: 10 · 2018: 10 · 2017: 8 · 2016: 5 · 2015: 9 · 2014: 11 · 2013: 4 · 2012: 11
- FWCI
- 1.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gene Therapy (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Infectious Diseases › Parvovirus B19 Infection Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- adeno-associated virus, site-specific integration, chromosome 19, recombinant AAV vectors, Rep78, Rep68, initiator protein, latent infection, target site selection, gene therapy vectors
- MeSH terms
- Dependovirus, Genetic Vectors, Humans, Transduction, Genetic, Genetic Therapy, Mutagenesis, Site-Directed, Virus Integration, Genome, Viral, Virus Latency
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
