Terminal differentiation of cardiac and skeletal myocytes induces permissivity to AAV transduction by relieving inhibition imposed by DNA damage response proteins
Open accessAbstract
Gene therapy vectors based on the adeno-associated virus (AAV) are extremely efficient for gene transfer into post-mitotic cells of heart, muscle, brain, and retina. The reason for their exquisite tropism for these cells has long remained elusive. Here, we show that upon terminal differentiation, cardiac and skeletal myocytes downregulate proteins of the DNA damage response (DDR) and that this markedly induces permissivity to AAV transduction. We observed that expression of members of the MRN complex (Mre11, Rad50, Nbs1), which bind the incoming AAV genomes, faded in cardiomyocytes at ~2 weeks after birth, as well as upon myoblast differentiation in vitro; in both cases, withdrawal of the cells from the cell cycle coincided with increased AAV permissivity. Treatment of proliferating cells with short-interfering RNAs (siRNAs) against the MRN proteins, or with microRNA-24, which is normally upregulated upon terminal differentiation and negatively controls the Nbs1 levels, significantly increased permissivity to AAV transduction. Consistently, delivery of these small RNAs to the juvenile liver concomitant with AAV markedly improved in vivo hepatocyte transduction. Collectively, these findings support the conclusion that cellular DDR proteins inhibit AAV transduction and that terminal cell differentiation relieves this restriction.
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Non-dividing terminally differentiated cells allow efficient expression from rAAV gene therapy vectors because the cells downregulate proteins of the DNA damage response.
“Non-dividing terminally differentiated cells allow efficient expression from rAAV gene therapy vectors because the cells downregulate proteins of the DNA damage response [312].”
From Recombinant Adeno-Associated Viral Vectors (rAAV)-Vector Elements in Ocular Gene Therapy Clinical Trials and Transgene Expression and Bioactivity Assays (2020) · cites this paper as [312]
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van Rooij, E., Sutherland, L. B., Liu, N., Williams, A. H., McAnally, J., Gerard, R. D., Richardson, J. A., & Olson, E. N. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608791103 · Cited by 1,498 · see citing works
Analysis of AAV Serotypes 1–9 Mediated Gene Expression and Tropism in Mice After Systemic Injection
Zincarelli, C., Soltys, S., Rengo, G., & Rabinowitz, J. E. (2008) · Molecular Therapy · doi:10.1038/mt.2008.76 · Cited by 1,490 · see citing works
Cheng, A. M. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki200 · Cited by 1,420 · see citing works
Pathways of DNA Double-Strand Break Repair during the Mammalian Cell Cycle
Rothkamm, K., Krüger, I., Thompson, L. H., & Lübrich, M. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.16.5706-5715.2003 · Cited by 1,187 · see citing works
Adeno-associated Virus Serotypes: Vector Toolkit for Human Gene Therapy
Wu, Z., Asokan, A., & Samulski, R. J. (2006) · Molecular Therapy · doi:10.1016/j.ymthe.2006.05.009 · Cited by 921 · see citing works
Xiao, X., Li, J., & Samulski, R. J. (1996) · Journal of Virology · doi:10.1128/jvi.70.11.8098-8108.1996 · Cited by 913 · see citing works
Therapeutic in vivo gene transfer for genetic disease using AAV: Progress and challenges
Mingozzi, F., & High, K. A. (2011) · Nature Reviews Genetics · doi:10.1038/nrg2988 · Cited by 893 · see citing works
Ferrari, F. K., Samulski, T., Shenk, T., & Samulski, R. J. (1996) · Journal of Virology · doi:10.1128/jvi.70.5.3227-3234.1996 · Cited by 761 · see citing works
The MRE11 complex: starting from the ends
Stracker, T. H., & Petrini, J. H. J. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3047 · Cited by 734 · see citing works
Inagaki, K., Fuess, S., Storm, T. A., Gibson, G. A., Mctiernan, C. F., Kay, M. A., & Nakai, H. (2006) · Molecular Therapy · doi:10.1016/j.ymthe.2006.03.014 · Cited by 610 · see citing works
Lal, A., Navarro, F., Maher, C. A., Maliszewski, L. E., Yan, N., O’Day, E. M., Chowdhury, D., Dykxhoorn, D. M., Tsai, P., Hofmann, O., et al. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.08.020 · Cited by 573 · see citing works
McCarty, D. M., Fu, H., Monahan, P. E., Toulson, C. E., Naik, P., & Samulski, R. J. (2003) · Gene Therapy · doi:10.1038/sj.gt.3302134 · Cited by 547 · see citing works
Fisher, K. J., Gao, G. P., Weitzman, M. D., DeMatteo, R. P., Burda, J. F., & Wilson, J. M. (1996) · Journal of Virology · doi:10.1128/jvi.70.1.520-532.1996 · Cited by 546 · see citing works
Mishra, P. J., Humeniuk, R., Mishra, P. J., Longo-Sorbello, G. S. A., Banerjee, D., & Bertino, J. R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706217104 · Cited by 417 · see citing works
Wang, Z., Ma, H.-I., Li, J., Sun, L., Zhang, J., & Xiao, X. (2003) · Gene Therapy · doi:10.1038/sj.gt.3302133 · Cited by 413 · see citing works
Arnaudeau, C., Lundin, C., & Helleday, T. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.4564 · Cited by 387 · see citing works
Role of mammalian Mre11 in classical and alternative nonhomologous end joining
Xie, A., Kwok, A., & Scully, R. (2009) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1640 · Cited by 351 · see citing works
Role of Mre11 in chromosomal nonhomologous end joining in mammalian cells
Rass, E., Grabarz, A., Plo, I., Gautier, J., Bertrand, P., & López, B. S. (2009) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1641 · Cited by 325 · see citing works
Cell cycle exit upon myogenic differentiation
Walsh, K., & Perlman, H. (1997) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(97)80005-6 · Cited by 325 · see citing works
Adeno-Associated Virus Vector Genomes Persist as Episomal Chromatin in Primate Muscle
Penaud‐Budloo, M., Guiner, C. L., Nowrouzi, A., Toromanoff, A., Chérel, Y., Chenuaud, P., Schmidt, M., Kalle, C. V., Rolling, F., Moullier, P., et al. (2008) · Journal of Virology · doi:10.1128/jvi.00649-08 · Cited by 319 · see citing works
Human gene targeting by viral vectors
Russell, D. W., & Hirata, R. K. (1998) · Nature Genetics · doi:10.1038/ng0498-325 · Cited by 316 · see citing works
The MRN complex: coordinating and mediating the response to broken chromosomes
van den Bosch, M., Bree, R. T., & Lowndes, N. F. (2003) · The EMBO Reports · doi:10.1038/sj.embor.embor925 · Cited by 289 · see citing works
p16INK4a Translation Suppressed by miR-24
Lal, A., Kim, H. H., Abdelmohsen, K., Kuwano, Y., Pullmann, R., Srikantan, S., Subrahmanyam, R., Martindale, J. L., Yang, X., Ahmed, F., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001864 · Cited by 268 · see citing works
Transforming growth factor- -regulated miR-24 promotes skeletal muscle differentiation
Sun, Q., Zhang, Y., Yang, G., Chen, X., Zhang, Y., Cao, G., Wang, J., Sun, Y., Zhang, Y., Fan, M., et al. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn032 · Cited by 261 · see citing works
Mre11 Complex and DNA Replication: Linkage to E2F and Sites of DNA Synthesis
Maser, R. S., Mirzoeva, O. K., Wells, J. M., Olivares, H. A., Williams, B. R., Zinkel, R. A., Farnham, P., & Petrini, J. H. J. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.17.6006-6016.2001 · Cited by 212 · see citing works
VandenDriessche, T., Thorrez, L., Acosta‐Sanchez, A., Petrus, I., Wang, L., Ma, L., Waele, L. D., Iwasaki, Y., Gillijns, V., Wilson, J. M., et al. (2006) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2006.02220.x · Cited by 210 · see citing works
Gene Delivery to the Juvenile Mouse Liver Using AAV2/8 Vectors.
Cunningham, S., Dane, A. P., Spinoulas, A., & Alexander, I. (2008) · Molecular Therapy · doi:10.1038/mt.2008.72 · Cited by 175 · see citing works
Notch1 signaling stimulates proliferation of immature cardiomyocytes
Collesi, C., Zentilin, L., Sinagra, G., & Giacca, M. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200806091 · Cited by 169 · 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
Systematic Evaluation of AAV Vectors for Liver directed Gene Transfer in Murine Models
Wang, L., Wang, H., Bell, P. L., McCarter, R., He, J., Calcedo, R., Vandenberghe, L. H., Morizono, H., Batshaw, M. L., & Wilson, J. M. (2009) · Molecular Therapy · doi:10.1038/mt.2009.246 · Cited by 135 · 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
Self-citationCell proliferation and renewal of normal hepatocytes and bile duct cells in adult mouse liver
Magami, Y., Azuma, T., Inokuchi, H., Kokuno, S., Moriyasu, F., Kawai, K., & Hattori, T. (2002) · Liver International · doi:10.1034/j.1600-0676.2002.01702.x · Cited by 124 · see citing works
Structure of Adeno-Associated Virus Vector DNA following Transduction of the Skeletal Muscle
Vincent, N., Snyder, R. O., Gluzman, R., Bohl, D., Lagarde, C., & Danos, O. (1999) · Journal of Virology · doi:10.1128/jvi.73.3.1949-1955.1999 · Cited by 112 · see citing works
Characterization of function and regulation of miR-24-1 and miR-31
Sun, F., Wang, J., Pan, Q., Yu, Y., Zhang, Y., Wan, Y., Wang, J., Li, X., & Hong, A. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.01.161 · Cited by 108 · see citing works
Zentilin, L., Marcello, A., & Giacca, M. (2001) · Journal of Virology · doi:10.1128/jvi.75.24.12279-12287.2001 · Cited by 108 · see citing works
Self-citationAutonomous and Growth Factor–Induced Hypertrophy in Cultured Neonatal Mouse Cardiac Myocytes
Deng, X.-F., Rokosh, G. D., & Simpson, P. C. (2000) · Circulation Research · doi:10.1161/01.res.87.9.781 · Cited by 107 · see citing works
Mishra, P. J., Song, B., Mishra, P. J., Wang, Y., Humeniuk, R., Banerjee, D., Merlino, G. T., Ju, J., & Bertino, J. R. (2009) · PLoS ONE · doi:10.1371/journal.pone.0008445 · Cited by 104 · see citing works
Chiang, Y.-C., Teng, S., Su, Y., Hsieh, F., & Wu, K. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212043200 · Cited by 91 · 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
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
Okuyama, T., Huber, R., Bowling, W. M., Pearline, R. V., Kennedy, S. C., Flye, M. W., & Ponder, K. P. (1996) · Human Gene Therapy · doi:10.1089/hum.1996.7.5-637 · Cited by 69 · see citing works
Şanlıoğlu, S., Benson, P. K., & Engelhardt, J. F. (2000) · Virology · doi:10.1006/viro.1999.0137 · Cited by 61 · see citing works
Rad50 Is Dispensable for the Maintenance and Viability of Postmitotic Tissues
Adelman, C. A., De, S., & Petrini, J. H. J. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01525-08 · Cited by 45 · see citing works
Cataldi, M., & Mccarty, D. (2010) · Journal of Virology · doi:10.1128/jvi.00641-10 · Cited by 42 · see citing works
Sipo, I., Fechner, H., Pinkert, S., Suckau, L., Wang, X., Weger, S., & Poller, W. C. (2007) · Gene Therapy · doi:10.1038/sj.gt.3302987 · Cited by 40 · see citing works
DNA damage and cellular differentiation: More questions than responses
Simonatto, M., Latella, L., & Puri, P. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21275 · Cited by 39 · see citing works
Expression pattern of the Nijmegen breakage syndrome gene, Nbs1, during murine development
Wilda, M. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.12.1739 · Cited by 38 · see citing works
Flageul, M., Aubert, D., Pichard, V., Nguyen, T. H., Nowrouzi, A., Schmidt, M., & Ferry, N. (2009) · The Journal of Gene Medicine · doi:10.1002/jgm.1343 · Cited by 28 · see citing works
Mouse RAD50 Has Limited Epitopic Homology to p53 and Is Expressed in the Adult Myocardium
Kim, K. K., DAUD, A. I., Wong, S. C., Pajak, L., Tsai, S.-C., Wang, H., Henzel, W. J., & Field, L. J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.46.29255 · Cited by 22 · see citing works
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Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic Approaches
Beermann, J., Piccoli, M.-T., Viereck, J., & Thum, T. (2016) · Physiological Reviews · doi:10.1152/physrev.00041.2015 · Cited by 1,727 · see citing works
AAV Vector Immunogenicity in Humans: A Long Journey to Successful Gene Transfer
Costa Verdera, H., Kuranda, K., & Mingozzi, F. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2019.12.010 · Cited by 641 · see citing works
Lesizza, P., Prosdocimo, G., Martinelli, V. C., Sinagra, G., Zacchigna, S., & Giacca, M. (2017) · Circulation Research · doi:10.1161/circresaha.116.309589 · Cited by 208 · see citing works
Self-citationAdeno-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 140 · see citing works
Self-citationSurface-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 134 · see citing works
Buck, T., & Wijnholds, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124197 · Cited by 92 · see citing works
“Non-dividing terminally differentiated cells allow efficient expression from rAAV gene therapy vectors because the cells downregulate proteins of the DNA damage response [312].”
BackgroundNon-coding RNA therapeutics for cardiac regeneration
Braga, L., Ali, H., Secco, I., & Giacca, M. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa071 · Cited by 97 · see citing works
Self-citationManso, A. M., Hashem, S. I., Nelson, B., Gault, E., Soto‐Hermida, A., Villarruel, E. E., Brambatti, M., Bogomolovas, J., Bushway, P., Chen, C., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aax1744 · Cited by 85 · see citing works
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 88 · see citing works
m6A epitranscriptomic regulation of tissue homeostasis during primate aging
Wu, Z., Lu, M., Liu, D., Shi, Y. X., Ren, J., Wang, S., Jing, Y., Zhang, S., Zhao, Q., Li, H., et al. (2023) · Nature Aging · doi:10.1038/s43587-023-00393-2 · Cited by 82 · see citing works
Cappellari, G. G., Zanetti, M., Semolic, A., Vinci, P., Ruozi, G., Falcione, A., Filigheddu, N., Guarnieri, G., Graziani, A., Giacca, M., et al. (2016) · Diabetes · doi:10.2337/db15-1019 · Cited by 77 · see citing works
Self-citationFelician, G., Collesi, C., Lušić, M., Martinelli, V. C., Ferro, M. D., Zentilin, L., Zacchigna, S., & Giacca, M. (2014) · Circulation Research · doi:10.1161/circresaha.115.304517 · Cited by 74 · see citing works
Self-citationJohansen, A. K., Molenaar, B., Versteeg, D., Leitoguinho, A. R., Demkes, C. J., Spanjaard, B., de Ruiter, H., Moqadam, F. A., Kooijman, L., Zentilin, L., et al. (2017) · Circulation Research · doi:10.1161/circresaha.116.310370 · Cited by 69 · see citing works
Self-citationPhysiological and Pharmacological Roles of FGF21 in Cardiovascular Diseases
Cheng, P., Zhang, F., Yu, L., Lin, X., He, L., Li, X., Lu, X., Yan, X., Tan, Y., & Zhang, C. (2016) · Journal of Diabetes Research · doi:10.1155/2016/1540267 · Cited by 67 · see citing works
Long‐Term miR‐669a Therapy Alleviates Chronic Dilated Cardiomyopathy in Dystrophic Mice
Quattrocelli, M., Crippa, S., Montecchiani, C., Camps, J., Cornaglia, A. I., Boldrin, L., Morgan, J. E., Calligaro, A., Casasco, A., Orlacchio, A., et al. (2013) · Journal of the American Heart Association · doi:10.1161/jaha.113.000284 · Cited by 63 · see citing works
Piras, B. A., Tian, Y., Xu, Y., Thomas, N. A., O’Connor, D. M., & French, B. A. (2016) · Gene Therapy · doi:10.1038/gt.2016.20 · Cited by 63 · 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
Zhang, C., Wang, F., Zhang, Y., Kang, Y., Wang, H., Si, M., Su, L., Xin, X., Xue, F., Hao, F., et al. (2015) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12709 · Cited by 59 · see citing works
Pryadkina, 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
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Bongianino, R., & Priori, S. (2015) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2015.61 · 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
Reversible Notch1 acetylation tunes proliferative signalling in cardiomyocytes
Collesi, C., Felician, G., Secco, I., Gutiérrez, M. I., Martelletti, E., Ali, H., Zentilin, L., Myers, M. P., & Giacca, M. (2017) · Cardiovascular Research · doi:10.1093/cvr/cvx228 · Cited by 47 · see citing works
Self-citationFattah, C., Nather, K., McCarroll, C. S., Hortigon-Vinagre, M. P., Zamora, V., Flores‐Muñoz, M., McArthur, L., Zentilin, L., Giacca, M., Touyz, R. M., et al. (2016) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2016.09.946 · Cited by 47 · see citing works
Self-citationCappellari, G. G., Semolic, A., Ruozi, G., Vinci, P., Guarnieri, G., Bortolotti, F., Barbetta, D., Zanetti, M., Giacca, M., & Barazzoni, R. (2017) · The FASEB Journal · doi:10.1096/fj.201700126r · Cited by 45 · see citing works
Self-citationDepletion of the Insulator Protein CTCF Results in Herpes Simplex Virus 1 Reactivation In Vivo
Washington, S. D., Edenfield, S., Lieux, C., Watson, Z. L., Taasan, S. M., Dhummakupt, A., Bloom, D. C., & Neumann, D. M. (2018) · Journal of Virology · doi:10.1128/jvi.00173-18 · Cited by 43 · see citing works
Jin, Q., Qiao, C., Li, J., Xiao, B., Li, J., & Xiao, X. (2019) · Skeletal Muscle · doi:10.1186/s13395-019-0197-y · Cited by 41 · see citing works
Inducing Endogenous Cardiac Regeneration: Can Biomaterials Connect the Dots?
Bar, A., & Cohen, S. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00126 · Cited by 40 · see citing works
Genome-wide RNAi screening identifies host restriction factors critical for in vivo AAV transduction
Mano, M., Ippodrino, R., Zentilin, L., Zacchigna, S., & Giacca, M. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1503607112 · Cited by 39 · see citing works
Self-citationHCE-T cell-based permeability model: A well-maintained or a highly variable barrier phenotype?
Juretić, M., Dukovski, B. J., Krtalić, I., Reichl, S., Cetina‐Čižmek, B., Filipović‐Grčić, J., Lovrić, J., & Pepić, I. (2017) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2017.03.018 · Cited by 33 · see citing works
Piras, B. A., O’Connor, D. M., & French, B. A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0075894 · Cited by 31 · see citing works
Kok, C. Y., Tsurusaki, S., Cabanes-Creus, M., Igoor, S., Rao, R., Skelton, R., Liao, S. H., Ginn, S., Knight, M., Scott, S., et al. (2023) · Molecular Therapy: Methods & Clinical Development · doi:10.1016/j.omtm.2023.08.010 · Cited by 28 · see citing works
Effects of bisphenol A exposure during cardiac cell differentiation
Escarda‐Castro, E., Herráez, M. P., & Lombó, M. (2021) · Environmental Pollution · doi:10.1016/j.envpol.2021.117567 · Cited by 29 · see citing works
Dupont, J.-B., Tournaire, B., Georger, C., Marolleau, B., Jeanson, L., Ledevin, M., Lindenbaum, P., Lecomte, É., Cogné, B., Dubreil, L., et al. (2015) · Molecular Therapy — Methods & Clinical Development · doi:10.1038/mtm.2015.10 · Cited by 23 · see citing works
Peraza-Vega, R. I., Valverde, M., & Rojas, E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23063231 · Cited by 20 · see citing works
Therapeutic applications of noncoding RNAs
Latronico, M. V. G., & Condorelli, G. (2015) · Current Opinion in Cardiology · doi:10.1097/hco.0000000000000162 · Cited by 19 · see citing works
Watson, Z. L., Ertel, M. K., Lewin, A. S., Tuli, S. S., Schultz, G. S., Neumann, D. M., & Bloom, D. C. (2016) · Journal of Virology · doi:10.1128/jvi.01028-16 · Cited by 17 · see citing works
Millet, R., Jolinon, N., Nguyen, X.-N., Berger, G., Cimarelli, A., Greco, A., Bertrand, P., Odenthal, M., Büning, H., & Salvetti, A. (2015) · Journal of Virology · doi:10.1128/jvi.00171-15 · Cited by 16 · see citing works
Li, Z., Wang, X., Janssen, J. M., Liu, J., Tasca, F., Hoeben, R. C., & Gonçalves, M. A. F. V. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae1213 · Cited by 15 · see citing works
Wu, Q.-X., de Isla, N., & Zhang, L. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26157384 · Cited by 14 · see citing works
Hao, S., Zhang, X., Ning, K., Feng, Z., Park, S. Y., Küz, Ç. A., McFarlin, S., Richart, D., Cheng, F., Zhang, E. Y., et al. (2023) · Journal of Virology · doi:10.1128/jvi.01330-23 · Cited by 15 · see citing works
Arabian, M., Azad, F. M., Maleki, M., & Malakootian, M. (2020) · PubMed Central · doi:10.22038/ijbms.2020.40974.10015 · Cited by 14 · see citing works
Gene therapy in monogenic congenital myopathies
Guan, X., Goddard, M. A., Mack, D. L., & Childers, M. K. (2015) · Methods · doi:10.1016/j.ymeth.2015.10.004 · Cited by 12 · see citing works
Moimas, S., Manasseri, B., Cuccia, G., d’Alcontres, F. S., Geuna, S., Pattarini, L., Zentilin, L., Giacca, M., & Colonna, M. R. (2015) · Journal of Tissue Engineering · doi:10.1177/2041731415611717 · Cited by 11 · see citing works
Self-citationPreparation of rAAV9 to Overexpress or Knockdown Genes in Mouse Hearts
Ding, J., Lin, Z., Jiang, J., Seidman, C. E., Seidman, J. G., Pu, W. T., & Wang, D. (2016) · Journal of Visualized Experiments · doi:10.3791/54787 · Cited by 11 · see citing works
Shanks, J. A., Herring, N., Johnson, E., Liu, K., Li, D., & Paterson, D. J. (2017) · Hypertension · doi:10.1161/hypertensionaha.116.08507 · Cited by 10 · see citing works
Use of Adeno-Associated Virus to Enrich Cardiomyocytes Derived from Human Stem Cells
Guan, X., Wang, Z., Czerniecki, S., Mack, D. L., François, V., Blouin, V., Moullier, P., & Childers, M. K. (2015) · Human Gene Therapy Clinical Development · doi:10.1089/humc.2015.052 · Cited by 10 · see citing works
Piccolo, P., Attanasio, S., Secco, I., Sangermano, R., Strisciuglio, C., Limongelli, G., Miele, E., Mutarelli, M., Banfi, S., Nigro, V., et al. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw365 · Cited by 9 · see citing works
Self-citationPinto, M. S.-L., Marti, L., Alarcón, J. F., Sitia, G., Fornaguera, C., Borrós, S., & Guerra‐Rebollo, M. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.113896 · Cited by 8 · see citing works
Casein kinase 2 activity is a host restriction factor for AAV transduction
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Notch pathway activation enhances cardiosphere in vitro expansion
Secco, I., Barile, L., Torrini, C., Zentilin, L., Vassalli, G., Giacca, M., & Collesi, C. (2018) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13832 · Cited by 7 · see citing works
Self-citationIn vivo rescue of genetic dilated cardiomyopathy by systemic delivery of nexilin
Shao, Y., Liu, C., Liao, H., Zhang, R., Yuan, B., Yang, H., Li, R., Zhu, S., Fang, X., Esteban, C. R., et al. (2024) · Genome biology · doi:10.1186/s13059-024-03283-x · Cited by 5 · see citing works
Interactions between noncoding RNAs as epigenetic regulatory mechanisms in cardiovascular diseases
Moukette, B. M., Barupala, N. P., Aonuma, T., Sepúlveda, M., Kawaguchi, S., & Kim, I. (2021) · Methods in cell biology · doi:10.1016/bs.mcb.2021.06.002 · Cited by 4 · see citing works
Cell Therapies and Gene Therapy for Diabetes: Current Progress
Ghassemifard, L., Hasanlu, M., Parsamanesh, N., Atkin, S. L., Almahmeed, W. A., & Sahebkar, A. (2024) · Current Diabetes Reviews · doi:10.2174/0115733998292392240425122326 · Cited by 4 · see citing works
Adeno-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
Volf, N., Vuerich, R., Colliva, A., Volpe, M. C., Marengon, M., Zentilin, L., Giacca, M., Ring, N., Vodret, S., Braga, L., et al. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.08.014 · Cited by 2 · see citing works
Self-citationDirected Evolution of AAV9 for Efficient Gene Expression in Cardiomyocytes In Vitro and In Vivo
Hüttermann, L., Schröder, L. C., Shetty, P. M. V., Jonker, T., Hille, S. S., Remes, A. K., Matzen, A., Boender, A., Grimm, D., Frank, D., et al. (2025) · Human Gene Therapy · doi:10.1089/hum.2024.126 · Cited by 2 · see citing works
Gene Therapy in Monogenic Congenital Myopathies
Guan, X., Goddard, M. A., Mack, D. L., & Childers, M. K. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-800548-4.00013-9 · Cited by 2 · see citing works
Hepatocarcinoma Angiogenesis and DNA Damage Repair Response: An Update
Long, X., Long, Z.-X., Huang, X., Yao, J., Xia, Q., & Deng, Y. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.82034 · Cited by 2 · see citing works
Wu, S., Xue, L., Li, X., Wang, Y., Zhu, Y., Luo, Y., Sun, J., Jin, T., Shu, W., & Wang, Z. (2025) · Immunologic Research · doi:10.1007/s12026-025-09609-6 · Cited by 1 · see citing works
López-García, M. Á., Feria-Romero, I. A., Segura-Uribe, J. J., Escalante-Santiago, D., & Orozco-Suárez, S. A. (2016) · Methods in pharmacology and toxicology · doi:10.1007/978-1-4939-6355-3_10 · Cited by 1 · see citing works
Gene Therapy for Neurological Diseases
Simonato, M., Wahlberg, L. U., Goins, W. F., & Glorioso, J. C. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-800563-7.00009-9 · Cited by 1 · see citing works
Use of adeno-associated virus to enrich cardiomyocytes derived from human stem cells
Guan, X., Wang, Z., Czerniecki, S., Mack, D. R., François, V., Blouin, V., Moullier, P., & Childers, M. K. (2015) · Human Gene Therapy Clinical Development · doi:10.1089/hum.2015.052 · Cited by 1 · see citing works
Li, X. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15793-6.00001-9 · Cited by 1 · see citing works
Gene therapy strategies for X-linked myotubular myopathy
Pierson, C. R. (2018) · Expert Opinion on Orphan Drugs · doi:10.1080/21678707.2018.1443807 · Cited by 1 · see citing works
Isolation and Characterisation of Relaxed Specificity I-TevI Nuclease Domain Mutants
Roy, A. C. (2015) · Scholarship@Western (Western University)
Neuropilin-1-Expressing Monocytes: Implications for Therapeutic Angiogenesis and Cancer Therapy
Zacchigna, S., & Giacca, M. (2017) · Springer eBooks · doi:10.1007/978-3-319-48824-0_12
Self-citationMelaku, L. S., & Debela, N. (2020) · Indian Journal of Health Sciences and Biomedical Research (KLEU) · doi:10.4103/kleuhsj.kleuhsj_92_20
Hao, S.-Y., Zhang, X., Ning, K., Feng, Z., Park, S. Y., Kuz, C. A., McFarlin, S., Richart, D., Cheng, F., Zhang, E. Y., et al. (2023) · bioRxiv · doi:10.1101/2023.09.27.559795 · Cited by 1 · see citing works
Gene Therapy for Genetic Muscle Diseases
Lee, J. W. (2023) · Korean Journal of Neuromuscular Disorders · doi:10.46518/kjnmd.2023.15.2.31
Shao, Y., Liu, C., Liao, H.-K., Zhang, R., Yuan, B., Yang, H., Li, R., Zhu, S., Fang, X., Rodrı́guez-Esteban, C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25893966
Shao, Y., Liu, C., Liao, H.-K., Zhang, R., Yuan, B., Yang, H., Li, R., Zhu, S., Fang, X., Rodrı́guez-Esteban, C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26724662
Shao, Y., Liu, C., Liao, H.-K., Zhang, R., Yuan, B., Yang, H., Li, R., Zhu, S., Fang, X., Rodrı́guez-Esteban, C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25893815
Shao, Y., Liu, C., Liao, H.-K., Zhang, R., Yuan, B., Yang, H., Li, R., Zhu, S., Fang, X., Rodrı́guez-Esteban, C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26724665
Yang, A., Chen, J., Liao, C., Miao, B., & Chen, S. (2026) · Virology · doi:10.1016/j.virol.2026.110819
Hydrogels loaded with different substances for treating heart failure: a promising therapy
Meng, R., Xiao, W., Liang, S., Shen, J., Xu, H., Li, H., Xue, X., Zheng, M., Wang, X., & Wei, M. (2026) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2026.1744301
- Authors
- Lovric, J., Mano, M., Zentilin, L., Eulalio, A., Zacchigna, S., & Giacca, M.
- Affiliations
- International Centre for Genetic Engineering and Biotechnology (IT)
- Corresponding author
- Giacca, Mauro
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2012-11
- Volume
- 20
- Issue
- 11
- Pages
- 2087-2097
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC3493462
- OpenAlex
- W2162955406
- Cited by
- 77
- References
- 49
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 9 · 2023: 6 · 2022: 1 · 2021: 2 · 2020: 7 · 2019: 2 · 2018: 3 · 2017: 7 · 2016: 9 · 2015: 17 · 2014: 3 · 2013: 4
- FWCI
- 4.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ArTS Archivio della ricerca di Trieste (University of Trieste https://www.units.it/) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Defense Acquisition Program Administration
- 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, AAV transduction, DNA damage response, terminal differentiation, cardiomyocytes, skeletal myocytes, MRN complex, MRE11, RAD50, NBS1, microRNA-24, hepatocyte transduction, siRNA knockdown, postmitotic cells, gene therapy vectors
- MeSH terms
- MRE11 Homologue Protein, Dependovirus, Animals, beta-Galactosidase, Cell Cycle, Cell Differentiation, DNA Damage, DNA-Binding Proteins, Heart, HeLa Cells, Humans, Liver, Nuclear Proteins, Transduction, Genetic, Down-Regulation, Acid Anhydride Hydrolases, Muscle Fibers, Skeletal, Gene Expression Regulation, Developmental, ATP-Binding Cassette Transporters, Cell Cycle Proteins, Myocytes, Cardiac, RNA, Small Interfering, MicroRNAs, DNA Repair Enzymes, Cell Proliferation, Mice, Rats, Gene Knockdown Techniques
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