Viral Single-Strand DNA Induces p53-Dependent Apoptosis in Human Embryonic Stem Cells
Open accessAbstract
Human embryonic stem cells (hESCs) are primed for rapid apoptosis following mild forms of genotoxic stress. A natural form of such cellular stress occurs in response to recombinant adeno-associated virus (rAAV) single-strand DNA genomes, which exploit the host DNA damage response for replication and genome persistence. Herein, we discovered a unique DNA damage response induced by rAAV transduction specific to pluripotent hESCs. Within hours following rAAV transduction, host DNA damage signaling was elicited as measured by increased gamma-H2AX, ser15-p53 phosphorylation, and subsequent p53-dependent transcriptional activation. Nucleotide incorporation assays demonstrated that rAAV transduced cells accumulated in early S-phase followed by the induction of apoptosis. This lethal signaling sequalae required p53 in a manner independent of transcriptional induction of Puma, Bax and Bcl-2 and was not evident in cells differentiated towards a neural lineage. Consistent with a lethal DNA damage response induced upon rAAV transduction of hESCs, empty AAV protein capsids demonstrated no toxicity. In contrast, DNA microinjections demonstrated that the minimal AAV origin of replication and, in particular, a 40 nucleotide G-rich tetrad repeat sequence, was sufficient for hESC apoptosis. Our data support a model in which rAAV transduction of hESCs induces a p53-dependent lethal response that is elicited by a telomeric sequence within the AAV origin of replication.
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?
The AAV ITR interacts with host proteins and can stimulate anti-viral and DNA damage response pathways.
“it is known that the AAV ITR interacts with a number of host proteins and can stimulate anti-viral and DNA damage response pathways.12–16”
From Adeno-Associated Virus Serotype-Specific Inverted Terminal Repeat Sequence Role in Vector Transgene Expression (2020) · cites this paper as [16]
The Introduction (page unavailable) attributes a DNA damage response after AAV infection to the ITR sequence, and reports checkpoint activation. The paper does not establish the other attributed points: that the ITR interacts with host proteins or stimulates anti-viral response pathways. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAAV vectors can induce DNA-damage responses in cells such as hematopoietic stem and progenitor cells, compromising transduction efficacy, viability and engraftment capacity in vivo.
“We and others have previously shown that AAV vectors can induce DNA-damage responses (DDR) in cells such as hematopoietic stem and progenitor cells (HSPCs), compromising the transduction efficacy, viability and engraftment capacity of these cells in vivo 26,28 .”
From AAV vectors trigger DNA damage response-dependent pro-inflammatory signalling in human iPSC-derived CNS models and mouse brain (2025) · cites this paper as [28]
Microinjection of human embryonic stem cells with oligonucleotides containing the ITR sequence was sufficient to induce DDR and apoptosis in these cells.
“In fact, microinjection of human embryonic stem cells with oligonucleotides containing the ITR sequence was sufficient to induce DDR and apoptosis in these cells 28 .”
From AAV vectors trigger DNA damage response-dependent pro-inflammatory signalling in human iPSC-derived CNS models and mouse brain (2025) · cites this paper as [28]
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
Direct Activation of Bax by p53 Mediates Mitochondrial Membrane Permeabilization and Apoptosis
Chipuk, J. E., Kuwana, T., Bouchier-Hayes, L., Droin, N. M., Newmeyer, D. D., Schuler, M., & Green, D. R. (2004) · Science · doi:10.1126/science.1092734 · Cited by 2,066 · cited 1× · see citing works
“transcription-independent apoptosis via localization to the cytoplasm and direct activation of Bax followed by cytochrome C release and caspase activation [2,26].”
BackgroundA ROCK inhibitor permits survival of dissociated human embryonic stem cells
Watanabe, K., Ueno, M., Kamiya, D., Nishiyama, A., Matsumura, M., Wataya, T., Takahashi, J. B., Nishikawa, S., Nishikawa, S.-I., Muguruma, K., et al. (2007) · Nature Biotechnology · doi:10.1038/nbt1310 · Cited by 2,055 · see citing works
p53- and ATM-Dependent Apoptosis Induced by Telomeres Lacking TRF2
Karlseder, J., Broccoli, D., Dai, Y., Hardy, S., & de Lange, T. (1999) · Science · doi:10.1126/science.283.5406.1321 · Cited by 1,086 · see citing works
Lost in Transcription: p21 Repression, Mechanisms, and Consequences
Gartel, A. L., & Radhakrishnan, S. K. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-3995 · Cited by 819 · see citing works
Low O 2 tensions and the prevention of differentiation of hES cells
Ezashi, T., Das, P., & Roberts, R. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501283102 · Cited by 804 · see citing works
McCarty, D., Monahan, P., & Samulski, R. (2001) · Gene Therapy · doi:10.1038/sj.gt.3301514 · Cited by 735 · see citing works
Self-citationGenomic alterations in cultured human embryonic stem cells
Maitra, A., Arking, D. E., Shivapurkar, N., Ikeda, M. A., Stastny, V., Kassauei, K., Sui, G., Cutler, D. J., Liu, Y., Constable, S., et al. (2005) · Nature Genetics · doi:10.1038/ng1631 · Cited by 617 · see citing works
Production and characterization of adeno-associated viral vectors
Grieger, J. C., Choi, V. W., & Samulski, R. J. (2006) · Nature Protocols · doi:10.1038/nprot.2006.207 · Cited by 567 · 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
Self-citationCellular senescence, cancer and aging: the telomere connection
Campisi, J., Kim, S.-H., Lim, C.-S., & Rubio, M. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(01)00160-7 · Cited by 400 · see citing works
Dravid, G. G., Ye, Z., Hammond, H., Chen, G., Pyle, A. D., Donovan, P. J., Yu, X., & Cheng, L. (2005) · Stem Cells · doi:10.1634/stemcells.2005-0034 · Cited by 339 · see citing works
Wobus, C. E., Hügle-Dörr, B., Girod, A., Petersen, G., Hallek, M., & Kleinschmidt, J. A. (2000) · Journal of Virology · doi:10.1128/jvi.74.19.9281-9293.2000 · Cited by 273 · cited 1× · see citing works
“It is important to note that the monoclonal A20 antibody recognizes an epitope unique to intact AAV2 capsids [37].”
BackgroundHong, Y., & Stambrook, P. J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401346101 · Cited by 248 · see citing works
Regulation of Apoptosis and Differentiation by p53 in Human Embryonic Stem Cells
Qin, H., Yu, T., Qing, T., Liu, Y., Zhao, Y., Cai, J., Li, J., Song, Z., Qu, X., Zhou, P., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m610464200 · Cited by 244 · see citing works
Virus-mediated killing of cells that lack p53 activity
Raj, K., Ogston, P., & Beard, P. (2001) · Nature · doi:10.1038/35091082 · Cited by 207 · see citing works
Using or abusing: viruses and the cellular DNA damage response
Lilley, C. E., Schwartz, R. A., & Weitzman, M. D. (2007) · Trends in Microbiology · doi:10.1016/j.tim.2007.01.003 · Cited by 207 · see citing works
Cosme‐Blanco, W., Shen, M., Lazar, A. J. F., Pathak, S., Lozano, G., Multani, A. S., & Chang, S. (2007) · The EMBO Reports · doi:10.1038/sj.embor.7400937 · Cited by 205 · see citing works
Hardin, C. C., Perry, A. G., & White, K. (2000) · Biopolymers · doi:10.1002/1097-0282(2000/2001)56:3 · Cited by 202 · see citing works
H2AX Is Required for Cell Cycle Arrest via the p53/p21 Pathway
Fragkos, M., Jurvansuu, J., & Beard, P. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01830-08 · Cited by 170 · see citing works
Enhancement of Adeno-Associated Virus Infection by Mobilizing Capsids into and Out of the Nucleolus
Johnson, J. S., & Samulski, R. J. (2008) · Journal of Virology · doi:10.1128/jvi.02309-08 · Cited by 158 · see citing works
Self-citationHost Cell DNA Repair Pathways in Adeno-Associated Viral Genome Processing
Choi, V. W., McCarty, D. M., & Samulski, R. J. (2006) · Journal of Virology · doi:10.1128/jvi.00841-06 · Cited by 144 · see citing works
Self-citationNeganova, I. E., Vilella, F., Atkinson, S. P., Lloret, M., Passos, J. F., von Zglinicki, T., O’Connor, J., Burks, D. J., Jones, R. C., Armstrong, L., et al. (2011) · Stem Cells · doi:10.1002/stem.620 · Cited by 140 · see citing works
Cell Cycle Regulation by MicroRNAs in Embryonic Stem Cells
Wang, Y., & Blelloch, R. H. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-0309 · Cited by 133 · see citing works
The Mre11/Rad50/Nbs1 complex limits adeno-associated virus transduction and replication
Schwartz, R. A., Palacios, J. A., Cassell, G. D., Adam, S., Giacca, M., & Weitzman, M. D. (2007) · Journal of Virology · doi:10.1128/jvi.01523-07 · Cited by 130 · see citing works
Engineering of human pluripotent stem cells by AAV-mediated gene targeting.
Khan, I., Hirata, R., Wang, P.-R., Li, Y., Kho, J., Nelson, A. M., Huo, Y., Zavaljevski, M., Ware, C., & Russell, D. (2010) · Molecular Therapy · doi:10.1038/mt.2010.55 · Cited by 126 · see citing works
Extension of G‐quadruplex DNA by ciliate telomerase
Oganesian, L., Moon, I. K., Bryan, T. M., & Jarstfer, M. B. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601006 · Cited by 117 · see citing works
Smith-Arica, J. R., Thomson, A. J., Ansell, R., Chiorini, J. A., Davidson, B. L., & McWhir, J. (2003) · Cloning and Stem Cells · doi:10.1089/153623003321512166 · Cited by 111 · see citing works
Human Parvovirus B19 Nonstructural Protein (NS1) Induces Cell Cycle Arrest at G 1 Phase
Morita, E., Nakashima, A., Asao, H., Sato, H., & Sugamura, K. (2003) · Journal of Virology · doi:10.1128/jvi.77.5.2915-2921.2003 · Cited by 98 · see citing works
p53 is required for etoposide-induced apoptosis of human embryonic stem cells
Grandela, C., Pera, M. F., & Wolvetang, E. J. (2007) · Stem Cell Research · doi:10.1016/j.scr.2007.10.003 · Cited by 86 · see citing works
Cervelli, T., Palacios, J. A., Zentilin, L., Mano, M., Schwartz, R. A., Weitzman, M. D., & Giacca, M. (2008) · Journal of Cell Science · doi:10.1242/jcs.003632 · Cited by 84 · see citing works
Human Embryonic Stem Cells Are Capable of Executing G1/S Checkpoint Activation
Bárta, T., Vinarský, V., Holubcová, Z., Bohačiaková, D., Verner, J., Pospı́šilová, Š., Dvořák, P., & Hampl, A. (2010) · Stem Cells · doi:10.1002/stem.451 · Cited by 83 · see citing works
Topoisomerase IIα maintains genomic stability through decatenation G2 checkpoint signaling
Bower, J. J., Karaca, G., Zhou, Y., Simpson, D. A., Cordeiro‐Stone, M., & Kaufmann, W. K. (2010) · Oncogene · doi:10.1038/onc.2010.232 · Cited by 83 · see citing works
Self-citationThe Role of DNA-PKcs and Artemis in Opening Viral DNA Hairpin Termini in Various Tissues in Mice
Inagaki, K., Ma, C.-R., Storm, T. A., Kay, M., & Nakai, H. (2007) · Journal of Virology · doi:10.1128/jvi.01225-07 · Cited by 76 · see citing works
Corbet, S. W., Clarke, A. R., Gledhill, S., & Wyllie, A. H. (1999) · Oncogene · doi:10.1038/sj.onc.1202436 · Cited by 75 · see citing works
Site-specific integration of adeno-associated virus involves partial duplication of the target locus
Henckaerts, E., Dutheil, N., Zeltner, N., Kattman, S. J., Kohlbrenner, E., Ward, P., Clément, N., Rebollo, P., Kennedy, M., Keller, G. M., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806821106 · Cited by 72 · see citing works
Gene targeting in human pluripotent stem cells with adeno-associated virus vectors
Mitsui, K., Suzuki, K., Aizawa, E., Kawase, E., Suemori, H., Nakatsuji, N., & Mitani, K. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.08.075 · Cited by 45 · see citing works
AAV Recombineering with Single Strand Oligonucleotides
Hirsch, M. L., Storici, F., Li, C., Choi, V. W., & Samulski, R. J. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007705 · Cited by 26 · see citing works
Self-citationCreating a Novel Origin of Replication through Modulating DNA-Protein Interfaces
Hewitt, F. C., & Samulski, R. J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008850 · Cited by 14 · see citing works
Self-citationVirus-mediated killing of cells that lack p53 activity
Nemunaitis, J. J., Senzer, N. N., Cunningham, C. C., & Dubensky, T. W. (2001) · Drug Resistance Updates · doi:10.1054/drup.2001.0220 · Cited by 12 · see citing works
addendum: Virus-mediated killing of cells that lack p53 activity
Raj, K., Ogston, P., & Beard, P. (2002) · Nature · doi:10.1038/416202a · Cited by 9 · see citing works
Host Cell DNA Repair Pathways in Adeno-Associated Viral Genome Processing
Choi, V. W., Samulski, R. J., & McCarty, D. M. (2020) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/dtap-1v96 · Cited by 9 · see citing works
Self-citationEnhancement of Adeno-Associated Virus Infection by Mobilizing Capsids into and Out of the Nucleolus
Johnson, J. S., & Samulski, R. J. (2020) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/vxkt-k936 · Cited by 4 · see citing works
Self-citation(2002) · Molecular Therapy · doi:10.1016/s1525-0016(16)42955-2 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Ellis, B. L., Hirsch, M. L., Barker, J. C., Connelly, J. P., Steininger, R. J., & Porteus, M. H. (2013) · Virology Journal · doi:10.1186/1743-422x-10-74 · Cited by 252 · see citing works
Self-citationEarley, L. F., Conatser, L. M., Lue, V. M., Dobbins, A. L., Li, C., Hirsch, M. L., & Samulski, R. J. (2020) · Human Gene Therapy · doi:10.1089/hum.2019.274 · Cited by 116 · see citing works
Self-citationAAV: An Overview of Unanswered Questions
Berns, K. I., & Muzyczka, N. (2017) · Human Gene Therapy · doi:10.1089/hum.2017.048 · Cited by 111 · see citing works
Dosage thresholds and influence of transgene cassette in adeno-associated virus–related toxicity
Khabou, H., Cordeau, C., Pacot, L., Fisson, S., & Dalkara, D. (2018) · Human Gene Therapy · doi:10.1089/hum.2018.144 · Cited by 93 · see citing works
AAV ablates neurogenesis in the adult murine hippocampus
Johnston, S., Parylak, S. L., Kim, S., Mac, N., Lim, C., Gallina, I., Bloyd, C., Newberry, A., Saavedra, C. D., Novak, O., et al. (2021) · eLife · doi:10.7554/elife.59291 · Cited by 87 · 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 92 · see citing works
Self-citationAdeno-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 88 · see citing works
Self-citationLiu, B., Behura, S. K., Clem, R. J., Schneemann, A., Becnel, J. J., Severson, D. W., & Zhou, L. J. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003137 · Cited by 85 · see citing works
Monosynaptic Tracing Success Depends Critically on Helper Virus Concentrations
Lavin, T. K., Jin, L., Lea, N. E., & Wickersham, I. R. (2020) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2020.00006 · Cited by 69 · see citing works
Effectiveness of gene delivery systems for pluripotent and differentiated cells
Rapti, K., Stillitano, F., Karakikes, I., Nonnenmacher, M. E., Weber, T., Hulot, J., & Hajjar, R. J. (2015) · Molecular Therapy — Methods & Clinical Development · doi:10.1038/mtm.2014.67 · Cited by 64 · see citing works
Oversized AAV Transductifon Is Mediated via a DNA-PKcs-independent, Rad51C-dependent Repair Pathway
Hirsch, M. L., Li, C., Bellon, I., Yin, C., Chavala, S., Pryadkina, M., Richard, I., & Samulski, R. J. (2013) · Molecular Therapy · doi:10.1038/mt.2013.184 · Cited by 62 · see citing works
Self-citationMa, Q., Deng, P., Zhu, G., Liu, C., Zhang, L., Zhou, Z., Luo, X. G., Li, M., Zhong, M., Yu, Z., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0090041 · Cited by 52 · see citing works
Protection from noise-induced cochlear synaptopathy by virally mediated overexpression of NT3
Hashimoto, K., Hickman, T. T., Suzuki, J., Ji, L., Kohrman, D. C., Corfas, G., & Liberman, M. C. (2019) · Scientific Reports · doi:10.1038/s41598-019-51724-6 · Cited by 49 · see citing works
Insight into the mechanism of inhibition of adeno-associated virus by the Mre11/Rad50/Nbs1 complex
Lentz, T. B., & Samulski, R. J. (2015) · Journal of Virology · doi:10.1128/jvi.01990-14 · Cited by 48 · see citing works
Self-citationAdeno-Associated Virus Vectors and Stem Cells: Friends or Foes?
Brown, N. J., Song, L., Rao, K. N., & Hirsch, M. L. (2017) · Human Gene Therapy · doi:10.1089/hum.2017.038 · Cited by 39 · see citing works
Self-citationCosta-Verdera, H., Meneghini, V., Fitzpatrick, Z., Abou Alezz, M., Fabyanic, E., Huang, X., Dzhashiashvili, Y., Ahiya, A., Mangiameli, E., Valeri, E., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-58778-3 · Cited by 32 · see citing works
Baik, R., Cromer, M. K., Glenn, S. E., Vakulskas, C. A., Chmielewski, K. O., Dudek, A. M., Feist, W. N., Klermund, J., Shipp, S., Cathomen, T., et al. (2024) · Nature Communications · doi:10.1038/s41467-023-43413-w · Cited by 32 · see citing works
Self-citationLiu, Y., Liu, W., Liu, K., Ao, L., Cao, J., Zhong, J. L., & Liu, J.-Y. (2015) · PLoS ONE · doi:10.1371/journal.pone.0139949 · Cited by 32 · see citing works
Dudek, A. M., & Porteus, M. H. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.660302 · Cited by 29 · see citing works
Self-citationAnalyzing efficacy, stability, and safety of AAV-mediated optogenetic hearing restoration in mice
Bali, B., Gruber-Dujardin, E., Kusch, K., Rankovic, V., & Moser, T. (2022) · Life Science Alliance · doi:10.26508/lsa.202101338 · Cited by 23 · see citing works
Bower, J., Song, L.-J., Bastola, P., & Hirsch, M. L. (2021) · Viruses · doi:10.3390/v13071205 · Cited by 15 · see citing works
Self-citationViral Generation, Packaging, and Transduction on a Digital Microfluidic Platform
Quach, A. B. V., Little, S. R., & Shih, S. C. C. (2022) · Analytical Chemistry · doi:10.1021/acs.analchem.1c05227 · Cited by 17 · see citing works
Adeno-Associated Virus Vector Mobilization, Risk Versus Reality
Song, L., Samulski, R. J., & Hirsch, M. L. (2020) · Human Gene Therapy · doi:10.1089/hum.2020.118 · Cited by 16 · see citing works
Self-citationAAV-Mediated Gene Editing via Double-Strand Break Repair
Hirsch, M. L., & Samulski, R. J. (2014) · Methods in molecular biology · doi:10.1007/978-1-62703-761-7_19 · Cited by 14 · see citing works
Self-citationGene Delivery to Human Limbal Stem Cells Using Viral Vectors
Song, L., Song, Z., Fry, N. J., Conatser, L., Llanga, T., Mei, H., Kafri, T., & Hirsch, M. L. (2019) · Human Gene Therapy · doi:10.1089/hum.2019.071 · Cited by 14 · see citing works
Self-citationBockstael, O., Melas, C., Pythoud, C., Levivier, M., McCarty, D. M., Samulski, R. J., Witte, O. D., & Tenenbaum, L. (2012) · Human Gene Therapy · doi:10.1089/hum.2011.216 · Cited by 14 · see citing works
Self-citationDudek, A. M., & Porteus, M. H. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.09.005 · Cited by 14 · see citing works
Self-citationTissue and cell-type-specific transduction using rAAV vectors in lung diseases
Kochergin-Nikitsky, K. S., Belova, L., Лавров, А. В., & Smirnikhina, S. (2021) · Journal of Molecular Medicine · doi:10.1007/s00109-021-02086-y · Cited by 13 · see citing works
Song, L., Hasegawa, T., Brown, N. J., Bower, J. J., Samulski, R. J., & Hirsch, M. L. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf013 · Cited by 12 · see citing works
Self-citationVinarský, V., Křivánek, J., Rankel, L., Nahácka, Z., Bárta, T., Jaroš, J., Anděra, L., & Hampl, A. (2013) · Stem Cells and Development · doi:10.1089/scd.2013.0057 · Cited by 13 · see citing works
Zubkova, E., Beloglazova, I. B., Ratner, E. I., Dyikanov, D. T., Дергилев, К. В., Menshikov, M. Y., & Parfyonova, Y. V. (2021) · Biology Open · doi:10.1242/bio.058461 · Cited by 12 · see citing works
Lkharrazi, A., Tobler, K., Marti, S., Bratus-Neuenschwander, A., Vogt, B., & Fraefel, C. (2024) · Journal of Virology · doi:10.1128/jvi.01282-24 · Cited by 12 · see citing works
Comparison of Ectopic Gene Expression Methods in Rat Neural Stem Cells
Kim, W., Kim, J. H., Kong, S.-Y., Park, M.-H., Sohn, U. D., & Kim, H. (2013) · Korean Journal of Physiology and Pharmacology · doi:10.4196/kjpp.2013.17.1.23 · Cited by 9 · see citing works
Gene Therapy for Hemophilia A: Where We Stand
Zhou, M., Hu, Z., Zhang, C., Wu, L., Li, Z., & Liang, D. (2020) · Current Gene Therapy · doi:10.2174/1566523220666200806110849 · Cited by 8 · see citing works
Small Genomes, Big Disruptions: Parvoviruses and the DNA Damage Response
Abrahams, R. R., & Majumder, K. (2025) · Viruses · doi:10.3390/v17040494 · Cited by 6 · see citing works
Summers, M. F., Haubold, M. K., Morgenstern, M., Shepherd, P. M., Larsen, C. I. S., Bartz, A. E., Thirumoorthy, G., Kirchdoerfer, R. N., Coon, J. J., Mehta, K. P. M., et al. (2025) · PLoS Pathogens · doi:10.1371/journal.ppat.1013142 · Cited by 5 · see citing works
McCall, T. F., Sawyer, E. J., Darnell, J., Hirsch, M. L., & Bower, J. J. (2025) · Molecular Therapy Oncology · doi:10.1016/j.omton.2025.201020 · Cited by 4 · see citing works
Self-citationAdeno-associated Virus as a Mammalian DNA Vector
Salganik, M., Hirsch, M. L., & Samulski, R. J. (2015) · ASM Press eBooks · doi:10.1128/9781555819217.ch37 · Cited by 4 · see citing works
Self-citationHalim, V. C., Bahader, I., Derstroff, D., Ullrich, C., Kuwabara, M. F., Hultqvist, G., Kusch, K., Slitin, L., Becker, L., de Angelis, M. H., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.11.664127 · Cited by 3 · see citing works
AAV vectors trigger DNA damage responses and STING-dependent inflammation in human CNS cells
Costa-Verdera, H., Meneghini, V., Fitzpatrick, Z., Alezz, M. A., Fabyanic, E., Huang, X., Dzhashiashvili, Y., Ahiya, A., Mangiameli, E., Valeri, E., et al. (2024) · doi:10.21203/rs.3.rs-4171795/v1 · Cited by 32 · see citing works
Du, C. (2022) · AIP conference proceedings · doi:10.1063/5.0093889 · Cited by 2 · see citing works
Unveiling Small Non‐Coding RNA Dynamics During Recombinant Adeno‐Associated Virus Production
Burkhart, M., Langenbach, K., Holzmann, K., Hornung, N., Baiz, J., & Otte, K. (2025) · Biotechnology Journal · doi:10.1002/biot.70092 · Cited by 1 · see citing works
Natsagdorj, M., Hara, H., Uosaki, H., Nakahara, F., Inoue, M., & Hanazono, Y. (2026) · Communications Biology · doi:10.1038/s42003-026-09604-z · Cited by 4 · see citing works
AAV transduction of human glioblastoma cell lines induces perturbation in cell proliferation
Wu, A. J., Dumo, C. J., Cook, W. H., Richards, I., Foliaki, J. M., Cooper, E., Fong, D. M., Mouravlev, A., Park, T. I., Dragunow, M., et al. (2026) · Molecular Therapy Oncology · doi:10.1016/j.omton.2026.201216 · Cited by 1 · see citing works
Stimulation of AAV Gene Editing via DSB Repair
Mitchell, A. M., Moser, R. J., Samulski, R. J., & Hirsch, M. L. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-1-4939-3509-3_8 · Cited by 1 · see citing works
Self-citationWild type AAV, recombinant AAV, and Adenovirus super infection impact on AAV vector mobilizationPreprint
Song, L., Samulski, R. J., & Hirsch, M. L. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.05.13.094201 · Cited by 1 · see citing works
Self-citationReply to “Efficient Nuclease-free HR by Clade F AAV Requires High MOIs with High Quality Vectors”
Rogers, G. L., Chen, H.-Y., Morales, H., & Cannon, P. M. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.11.003
Lkharrazi, A., Tobler, K., Marti, S., Bratus-Neuenschwander, A., Vogt, B., & Fraefel, C. (2023) · bioRxiv · doi:10.1101/2023.11.13.566888
rAAV-Mediated Gene Therapy Targeting CNS Disorders
Suárez-Amarán, L., Chatzi, C. A., Flier, I., & Samulski, R. J. (2025) · Springer eBooks · doi:10.1007/978-3-031-89307-0_2
Self-citationDevelopment of safe and efficient aav vectors for retinal gene therapy
Khabou, H. (2018) · theses.fr (ABES) · doi:10.70675/aa896663z9772z4d87z9bd1z247af1f0e3f1
abdelnaby, M., Galiakberova, A. A., & Dashinimaev, E. B. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27156846
Park, H., Jung, Y. M., Choi, H. J., Song, H., & Kim, Y. (2026) · Research Square · doi:10.21203/rs.3.rs-10990457/v1
- Authors
- Hirsch, M. L., Fagan, B. M., Dumitru, R., Bower, J. J., Yadav, S., Porteus, M. H., Pevny, L. H., & Samulski, R. J.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Stanford University (US)
- Corresponding author
- Hirsch, Matthew L.
- Samulski, R. Jude
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-11-17
- Volume
- 6
- Issue
- 11
- Pages
- e27520
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3219675
- OpenAlex
- W2063552605
- Cited by
- 53
- References
- 41
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 5 · 2020: 5 · 2019: 4 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 4 · 2014: 3 · 2013: 5 · 2012: 2
- FWCI
- 2.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, public-domain)
- Europe PMC (PubMed Central) (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- UNC Libraries
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL051818, P01HL051818, P01HL066973, HL 066973)
- National Institute of General Medical Sciences (GM0529299)
- National Institute of Allergy and Infectious Diseases (R01AI072176, AI072176)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- human embryonic stem cells, adeno-associated virus, single-stranded DNA, p53-dependent apoptosis, DNA damage response, telomeric sequences, γH2AX, pluripotency, neuronal differentiation
- MeSH terms
- Dependovirus, Cells, Cultured, DNA Damage, DNA Replication, DNA, Single-Stranded, Fibroblasts, Flow Cytometry, Fluorescent Antibody Technique, Histones, Humans, Phosphorylation, RNA, Messenger, Blotting, Western, Signal Transduction, Tumor Suppressor Protein p53, Apoptosis, Embryonic Stem Cells, Real-Time Polymerase Chain Reaction
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
