The woodchuck hepatitis virus post-transcriptional regulatory element reduces readthrough transcription from retroviral vectors
Abstract
The woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) increases transgene expression from a variety of viral vectors, although the precise mechanism is not known. WPRE is most effective when placed downstream of the transgene, proximal to the polyadenylation signal. We hypothesized that WPRE likely reduces viral mRNA readthrough transcription by improving transcript termination, which in turn would increase viral titers and expression. Using a Cre-lox-mediated plasmid-based assay, we found significant readthrough transcription from gamma-retroviral vector (RV) long terminal repeat (wt RV-LTR) and RV LTR with a self-inactivating deletion (SIN RV-LTR). WPRE, when placed upstream of the RV LTRs, significantly reduced readthrough transcription. Readthrough, present at much lower levels with the SIN HIV-1 LV-LTR, was also reduced with WPRE. When placed in RV vectors, WPRE increased total RV genomic mRNA; and increased viral titers from transiently transfected 293T cells and stable PG13 producer cells by 7- to 15-fold. The mechanism of increased titers and expression was not due to increased nuclear mRNA export, increased rate of viral transcription or a significant increase in viral mRNA half-life. Our results showed that WPRE improved vector genomic transcript termination to increase titers and expression from RVs.
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WPRE is often included in AAV cassettes to improve viral titer and transduction efficiency via stabilizing mRNA and regulating transcriptional termination.
“The woodchuck hepatitis post-transcriptional regulatory element (WPRE) is often included in AAV cassettes to improve viral titer and transduction efficiency via stabilizing mRNA and regulating transcriptional termination [26, 27].”
From Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside (2024) · cites this paper as [27]
Cites
In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral Vector
Naldini, L., Blömer, U., Gallay, P., Ory, D., Mulligan, R., Gage, F. H., Verma, I. M., & Trono, D. (1996) · Science · doi:10.1126/science.272.5259.263 · Cited by 4,903 · see citing works
Zufferey, R., Donello, J. E., Trono, D., & Hope, T. J. (1999) · Journal of Virology · doi:10.1128/jvi.73.4.2886-2892.1999 · Cited by 1,012 · see citing works
A transient three-plasmid expression system for the production of high titer retroviral vectors
Soneoka, Y., Cannon, P. M., Ramsdale, E. E., Griffiths, J. C., Romano, G., Kingsman, S. M., & Kingsman, A. J. (1995) · Nucleic Acids Research · doi:10.1093/nar/23.4.628 · Cited by 686 · see citing works
Woodchuck hepatitis virus contains a tripartite posttranscriptional regulatory element
Donello, J. E., Loeb, J. E., & Hope, T. J. (1998) · Journal of Virology · doi:10.1128/jvi.72.6.5085-5092.1998 · Cited by 350 · see citing works
Loeb, J. E., Cordier, W. S., Harris, M. E., Weitzman, M. D., & Hope, T. J. (1999) · Human Gene Therapy · doi:10.1089/10430349950016942 · Cited by 279 · see citing works
Inefficient processing impairs release of RNA from the site of transcription
Custódio, N., Carmo‐Fonseca, M., Geraghty, F., Periera, H. S., Grosveld, F. G., & Antoniou, M. N. (1999) · The EMBO Journal · doi:10.1093/emboj/18.10.2855 · Cited by 220 · see citing works
Schambach, A., Wodrich, H., Hildinger, M., Bohne, J., Kräusslich, H.-G., & Baum, C. (2000) · Molecular Therapy · doi:10.1006/mthe.2000.0191 · Cited by 194 · see citing works
Krall, W. J., Challita, P. M., Perlmutter, L., Skelton, D. C., & Kohn, D. B. (1994) · Blood · doi:10.1182/blood.v83.9.2737.2737 · Cited by 163 · see citing works
Self-citationHuang, Z., & Yen, T. S. B. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.7.3864 · Cited by 149 · see citing works
Schambach, A., Bohne, J., Baum, C., Hermann, F. G., Egerer, L., von Laer, D., & Giroglou, T. (2005) · Gene Therapy · doi:10.1038/sj.gt.3302698 · Cited by 145 · see citing works
Robbins, P. B., Skelton, D. C., Yu, X., Halene, S., Leonard, E. H., & Kohn, D. B. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.17.10182 · Cited by 139 · see citing works
Self-citationRNA 3′ Readthrough of Oncoretrovirus and Lentivirus: Implications for Vector Safety and Efficacy
Zaiss, A. K., Son, S., & Chang, L. (2002) · Journal of Virology · doi:10.1128/jvi.76.14.7209-7219.2002 · Cited by 135 · see citing works
Self-citationIsolation of a recombinant murine leukemia virus utilizing a new primer tRNA
Colicelli, J., & Goff, S. P. (1986) · Journal of Virology · doi:10.1128/jvi.57.1.37-45.1986 · Cited by 125 · see citing works
Moreau‐Gaudry, F., Xia, P., Jiang, G., Perelman, N., Bauer, G., Ellis, J., Surinya, K. H., Mavilio, F., Shen, C.-K. J., & Malik, P. (2001) · Blood · doi:10.1182/blood.v98.9.2664 · Cited by 115 · see citing works
Self-citationIntronless mRNA transport elements may affect multiple steps of pre‐mRNA processing
Huang, Y., Wimler, K. M., & Carmichael, G. (1999) · The EMBO Journal · doi:10.1093/emboj/18.6.1642 · Cited by 112 · see citing works
Mogen, B. D., MacDonald, M. H., Graybosch, R. A., & Hunt, A. G. (1990) · The Plant Cell · doi:10.1105/tpc.2.12.1261 · Cited by 95 · see citing works
The hepatitis B virus posttranscriptional regulatory element is composed of two subelements
Donello, J. E., Beeche, A. A., Smith, G. J., Lucero, G. R., & Hope, T. J. (1996) · Journal of Virology · doi:10.1128/jvi.70.7.4345-4351.1996 · Cited by 91 · see citing works
Schek, N., Cooke, C., & Alwine, J. C. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.12.5386 · Cited by 85 · see citing works
Malik, P., McQuiston, S. A., Yu, X., Pepper, K. A., Krall, W. J., Podsakoff, G. M., Kurtzman, G. J., & Kohn, D. B. (1997) · Journal of Virology · doi:10.1128/jvi.71.3.1776-1783.1997 · Cited by 83 · see citing works
Self-citationCRM1-Dependent Function of a cis-Acting RNA Export Element
Popa, I., Harris, M. E., Donello, J. E., & Hope, T. J. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.7.2057-2067.2002 · Cited by 82 · see citing works
WPRE-mediated enhancement of gene expression is promoter and cell line specific
Klein, R., Ruttkowski, B., Knapp, E., Salmons, B., Günzburg, W. H., & Hohenadl, C. (2006) · Gene · doi:10.1016/j.gene.2005.12.018 · Cited by 81 · see citing works
Zang, W.-Q., Fieno, A. M., Grant, R. A., & Yen, T. S. B. (1998) · Virology · doi:10.1006/viro.1998.9255 · Cited by 76 · see citing works
Valsamakis, A., Schek, N., & Alwine, J. C. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.9.3699 · Cited by 70 · see citing works
Russnak, R. (1991) · Nucleic Acids Research · doi:10.1093/nar/19.23.6449 · Cited by 57 · see citing works
Mastroyiannopoulos, N. P., Feldman, M. L., Uney, J. B., Mahadevan, M. S., & Phylactou, L. A. (2005) · EMBO Reports · doi:10.1038/sj.embor.7400390 · Cited by 49 · see citing works
Xu, Z., Mizuguchi, H., Mayumi, T., & Hayakawa, T. (2003) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/s0304-4165(03)00078-3 · Cited by 43 · see citing works
Cherrington, J. M., Russnak, R., & Ganem, D. (1992) · Journal of Virology · doi:10.1128/jvi.66.12.7589-7596.1992 · Cited by 39 · see citing works
Cellular Proteins That Bind to the Hepatitis B Virus Posttranscriptional Regulatory Element
Huang, Z., Zang, W.-Q., & Yen, T. S. B. (1996) · Virology · doi:10.1006/viro.1996.0152 · Cited by 38 · see citing works
Hlavatý, J., Schittmayer, M., Stracke, A., Jandl, G., Knapp, E., Felber, B. K., Salmons, B., Günzburg, W. H., & Renner, M. (2005) · Virology · doi:10.1016/j.virol.2005.06.037 · Cited by 33 · see citing works
Graveley, B. R., & Gilmartin, G. M. (1996) · Journal of Virology · doi:10.1128/jvi.70.3.1612-1617.1996 · Cited by 32 · see citing works
A human U2 RNA mutant stalled in 3' end processing is impaired in nuclear import
Huang, Q. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.4.1025 · Cited by 30 · see citing works
Malik, P., Krall, W. J., Yu, X., Zhou, C., & Kohn, D. B. (1995) · Blood · doi:10.1182/blood.v86.8.2993.2993 · Cited by 26 · see citing works
Self-citationAmino Acids Responsible for Decreased 2, 3-Biphosphosphoglycerate Binding to Fetal Hemoglobin
Adachi, K., Konitzer, P., Pang, J., Reddy, K. S., & Surrey, S. (1997) · Blood · doi:10.1182/blood.v90.8.2916 · Cited by 24 · see citing works
Increased in vitro and in vivo transgene expression levels mediated through cis‐acting elements
Johansen, J. L., Tornøe, J., Møller, A., & Johansen, T. E. (2003) · The Journal of Gene Medicine · doi:10.1002/jgm.444 · Cited by 22 · see citing works
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Beane, O. S., Fonseca, V. C., Cooper, L. L., Koren, G., & Darling, E. M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0115963 · Cited by 325 · see citing works
Lentiviral Vectors to Probe and Manipulate the Wnt Signaling Pathway
Fuerer, C., & Nusse, R. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009370 · Cited by 287 · see citing works
Biosafety Features of Lentiviral Vectors
Schambach, A., Zychlinski, D., Ehrnstroem, B., & Baum, C. (2013) · Human Gene Therapy · doi:10.1089/hum.2012.229 · Cited by 173 · see citing works
Viral Vectors: The Road to Reducing Genotoxicity
David, R. M., & Doherty, A. (2016) · Toxicological Sciences · doi:10.1093/toxsci/kfw220 · Cited by 170 · see citing works
State-of-the-Art Lentiviral Vectors for Research Use: Risk Assessment and Biosafety Recommendations
Pauwels, K., Gijsbers, R., Toelen, J., Schambach, A., Willard-Gallo, K. E., Verheust, C., Debyser, Z., & Herman, P. (2009) · Current Gene Therapy · doi:10.2174/156652309790031120 · Cited by 124 · see citing works
New developments in lentiviral vector design, production and purification
Segura, M. M., Mangion, M., Gaillet, B., & Garnier, A. (2013) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2013.779249 · Cited by 119 · see citing works
Designing Lentiviral Vectors for Gene Therapy of Genetic Diseases
Poletti, V., & Mavilio, F. (2021) · Viruses · doi:10.3390/v13081526 · Cited by 105 · see citing works
CAR-T cell potency: from structural elements to vector backbone components
Mazinani, M., & Rahbarizadeh, F. (2022) · Biomarker Research · doi:10.1186/s40364-022-00417-w · Cited by 105 · see citing works
Emery, D. W. (2011) · Human Gene Therapy · doi:10.1089/hum.2010.233 · Cited by 92 · see citing works
Zanta, M.-A., Charrier, S., Brice-Ouzet, A., Martin, S., Opolon, P., Thrasher, A. J., Hope, T. J., & Galy, A. H. M. (2009) · Gene Therapy · doi:10.1038/gt.2009.3 · Cited by 86 · see citing works
Lin, P. Y., Lin, Y., Lennon, D. P., Correa, D., SCHLUCHTER, M. D., & Caplan, A. I. (2012) · Stem Cells Translational Medicine · doi:10.5966/sctm.2012-0086 · Cited by 83 · see citing works
Avoiding cytotoxicity of transposases by dose-controlled mRNA delivery
Galla, M., Schambach, A., Falk, C. S., Maetzig, T., Kuehle, J., Lange, K., Zychlinski, D., Heinz, N., Brugman, M. H., Göhring, G., et al. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr384 · Cited by 73 · see citing works
Use of HIV as a gene transfer vector.
Pluta, K. D., & Kacprzak, M. M. (2009) · Acta Biochimica Polonica · doi:10.18388/abp.2009_2490 · Cited by 68 · see citing works
Mechanism of Reduction in Titers From Lentivirus Vectors Carrying Large Inserts in the 3′LTR
Urbinati, F., Arumugam, P. I., Higashimoto, T., Perumbeti, A., Mitts, K., Xia, P., & Malik, P. (2009) · Molecular Therapy · doi:10.1038/mt.2009.89 · Cited by 67 · see citing works
Self-citationAdeno-Associated Viral Gene Therapy for Inherited Retinal Disease
Ong, T., Pennesi, M. E., Birch, D. G., Lam, B. L., & Tsang, S. H. (2019) · Pharmaceutical Research · doi:10.1007/s11095-018-2564-5 · Cited by 66 · see citing works
Avoiding cytotoxicity of transposases by dose-controlled mRNA delivery
Galla, M., Schambach, A., Falk, C. S., Maetzig, T., Kuehle, J., Lange, K., Zychlinski, D., Heinz, N., Brugman, M. H., Göhring, G., et al. (2012) · Nucleic Acids Research · doi:10.1093/nar/gkr1266 · Cited by 59 · see citing works
Patrício, M. I., Barnard, A. R., Orlans, H. O., McClements, M. E., & MacLaren, R. E. (2017) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2016.12.006 · Cited by 59 · see citing works
Transient Retrovirus-Based CRISPR/Cas9 All-in-One Particles for Efficient, Targeted Gene Knockout
Knopp, Y., Geis, F. K., Heckl, D., Horn, S., Neumann, T., Kuehle, J., Meyer, J., Fehse, B., Baum, C., Morgan, M. A., et al. (2018) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2018.09.006 · Cited by 58 · see citing works
Palfi, A., Millington‐Ward, S., Chadderton, N., O’Reilly, M., Goldmann, T., Humphries, M. M., Li, T., Uwe Wolfrum, B., Humphries, P., Kenna, P. F., et al. (2009) · Human Gene Therapy · doi:10.1089/hum.2009.119 · Cited by 56 · see citing works
Xu, L., Yao, S., Ding, Y. E., Xie, M., Feng, D., Sha, P., Tan, L., Bei, F., & Yao, Y. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05661-2 · Cited by 48 · see citing works
Ottaviano, G., & Qasim, W. (2025) · Leukemia · doi:10.1038/s41375-025-02585-8 · Cited by 44 · see citing works
Genetic Therapy for Beta-Thalassemia: From the Bench to the Bedside
Arumugam, P. I., & Malik, P. (2010) · Hematology · doi:10.1182/asheducation-2010.1.445 · Cited by 40 · see citing works
Self-citationGenetic modification of lymphocytes by retrovirus-based vectors
Suerth, J. D., Schambach, A., & Baum, C. (2012) · Current Opinion in Immunology · doi:10.1016/j.coi.2012.08.007 · Cited by 38 · see citing works
Zeng, J., Du, J., Lin, J., Bak, X. Y., Wu, C., & Wang, S. (2009) · Molecular Therapy · doi:10.1038/mt.2009.124 · Cited by 38 · see citing works
Evolving Lessons on Nanomaterial-Coated Viral Vectors for Local and Systemic Gene Therapy
Kasala, D., Yoon, A. R., Hong, J., Kim, S. W., & Yun, C. (2016) · Nanomedicine · doi:10.2217/nnm-2016-0060 · Cited by 38 · see citing works
Larson, S. M., Truscott, L. C., Chiou, T., Patel, A., Kao, R. L., Tu, A. A., Tyagi, T., Lü, X., Elashoff, D. A., & Oliveira, S. N. D. (2017) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2016.1268745 · Cited by 32 · see citing works
Strategies to improve safety profile of AAV vectors
Suoranta, T., Laham-Karam, N., & Ylä‐Herttuala, S. (2022) · Frontiers in Molecular Medicine · doi:10.3389/fmmed.2022.1054069 · Cited by 30 · see citing works
The transformative potential of HSC gene therapy as a genetic medicine
Sagoo, P., & Gaspar, H. B. (2021) · Gene Therapy · doi:10.1038/s41434-021-00261-x · Cited by 26 · 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
Sustained Expression from DNA Vectors
Wong, S. P., Argyros, O., & Harbottle, R. P. (2014) · Advances in genetics · doi:10.1016/bs.adgen.2014.11.002 · Cited by 26 · see citing works
The design of retroviral vectors used in the CAR‐T products, risk management, and future perspective
Yin, H., & Wei, X.-J. (2025) · MedComm · doi:10.1002/mco2.70067 · Cited by 25 · see citing works
McKee, K. K., & Yurchenco, P. D. (2022) · JCI Insight · doi:10.1172/jci.insight.158397 · Cited by 23 · see citing works
Chu, T. L., Chen, P., Yu, A. X., Kong, M., Tan, Z., Tsang, K. Y., Zhou, Z., & Cheah, K. S. E. (2023) · eLife · doi:10.7554/elife.82142 · Cited by 20 · see citing works
Boulaire, J., Balani, P., & Wang, S. (2009) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2009.02.007 · Cited by 21 · see citing works
Genetically engineered birds; pre-CRISPR and CRISPR era
Dehdilani, N., Taemeh, S. Y., Goshayeshi, L., & Dehghani, H. (2021) · Biology of Reproduction · doi:10.1093/biolre/ioab196 · Cited by 21 · see citing works
Advances in Recombinant Adeno-Associated Virus Vectors for Neurodegenerative Diseases
Li, L., Vasan, L., Kartono, B., Clifford, K. P., Attarpour, A., Sharma, R., Mandrozos, M., Kim, A., Zhao, W., Belotserkovsky, A., et al. (2023) · Biomedicines · doi:10.3390/biomedicines11102725 · Cited by 19 · see citing works
Generation of High-Titer Self-Inactivated γ-Retroviral Vector Producer Cells
Ghani, K., Boivin-Welch, M., Roy, S., Piaceski, A. D., Barbier, M. A., Pope, E., Germain, L., & Caruso, M. (2019) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2019.05.013 · Cited by 20 · see citing works
Prevention of transgene silencing during human pluripotent stem cell differentiation
Uenaka, T., Napole, A., Saha, A., Sun, D., Singavarapu, A., Calzada, E., Chen, J., Erlebach, L., McQuade, A., Ramos, D. M., et al. (2026) · Cell stem cell · doi:10.1016/j.stem.2026.01.007 · Cited by 20 · see citing works
Kitazawa, T., Minoux, M., Ducret, S., & Rijli, F. M. (2022) · Journal of Developmental Biology · doi:10.3390/jdb10010009 · Cited by 16 · see citing works
Chen, X., Gao, W., Gambotto, A. A., & Finn, O. J. (2008) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-008-0624-0 · Cited by 15 · see citing works
HIV-1-Based Lentiviral Vectors
Liu, Y. P., & Berkhout, B. (2013) · Methods in molecular biology · doi:10.1007/978-1-62703-670-2_22 · Cited by 15 · see citing works
Lentiviral Vectors: From Wild-Type Viruses to Efficient Multi-Functional Delivery Vectors
Arrasate, A., Lopez-Robles, C., Zuazo, M., Baños-Mateos, S., Martı́n, C., Lamsfus‐Calle, A., & Fertin, M. J. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26178497 · Cited by 14 · see citing works
Elements of lentiviral vector design toward gene therapy for treating mucopolysaccharidosis I
Ou, L., Przybilla, M. J., Koniar, B. L., & Whitley, C. B. (2016) · Molecular Genetics and Metabolism Reports · doi:10.1016/j.ymgmr.2015.11.004 · Cited by 14 · see citing works
Develop an efficient and specific AAV-based labeling system for Muller glia in mice
Gao, Y., Fang, K., Yan, Z., Zhang, H., Geng, G., Wu, W., Ding, X., Zhang, H., Zhong, N., Wang, Q., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-27013-0 · Cited by 13 · see citing works
Improved microRNA suppression by WPRE-linked tough decoy microRNA sponges
Hollensen, A. K., Thomsen, R., Bak, R. O., Petersen, C. C., Ermegaard, E. R., Aagaard, L., Damgaard, C. K., & Mikkelsen, J. G. (2017) · RNA · doi:10.1261/rna.061192.117 · Cited by 13 · see citing works
Retrovirus-Based mRNA Transfer for Transient Cell Manipulation
Galla, M., Schambach, A., & Baum, C. (2012) · Methods in molecular biology · doi:10.1007/978-1-62703-260-5_10 · Cited by 13 · see citing works
ExportAid: database of RNA elements regulating nuclear RNA export in mammals
Giulietti, M., Milantoni, S. A., Armeni, T., Principato, G., & Piva, F. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu620 · Cited by 12 · see citing works
Dodd, M., Marquez‐Curtis, L. A., Janowska‐Wieczorek, A., & Hortelano, G. (2014) · The Journal of Gene Medicine · doi:10.1002/jgm.2769 · Cited by 11 · see citing works
Comparison of Lentiviral Packaging Mixes and Producer Cell Lines for RNAi Applications
Albrecht, C. H., Hosiner, S., Tichy, B., Aldrian, S. M., Hajdú, Š., & Nürnberger, S. (2015) · Molecular Biotechnology · doi:10.1007/s12033-015-9843-8 · Cited by 10 · see citing works
Richard, É., Lalanne, M., Lamrissi‐Garcia, I., Guyonnet‐Dupérat, V., Richard, E., Pitard, V., Mazurier, F., Moreau‐Gaudry, F., Ged, C., & de Verneuil, H. (2010) · The Journal of Gene Medicine · doi:10.1002/jgm.1478 · Cited by 10 · see citing works
Fan, X., Truong, J. B., Okada, K., Lin, H., Ori-McKenney, K. M., & McKenney, R. J. (2026) · Communications Biology · doi:10.1038/s42003-026-10797-6 · Cited by 9 · see citing works
The Post-Transcriptional Regulatory Element of Hepatitis B Virus: From Discovery to Therapy
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Luchicchi, A., Pattij, T., Viaña, J. N. M., de Kloet, S. F., & Marchant, N. J. (2020) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2020.109004 · Cited by 7 · see citing works
Neural development in human embryonic stem cells-applications of lentiviral vectors
Dottori, M., Tay, C. Y., & Hughes, S. M. (2011) · Journal of Cellular Biochemistry · doi:10.1002/jcb.23116 · Cited by 7 · see citing works
Lentiviral vectors with amplified β cell-specific gene expression
Shaw, K. L., Pais, E., Ge, S., Hardee, C. L., Skelton, D. C., Hollis, R. P., Crooks, G. M., & Kohn, D. B. (2009) · Gene Therapy · doi:10.1038/gt.2009.49 · Cited by 7 · see citing works
Self-citationOjiro, I., Katsuyama, H., Kaneko, R., Ogasawara, S., Murata, T., Terada, Y., & Ito, K. (2024) · PLoS ONE · doi:10.1371/journal.pone.0306029 · Cited by 6 · see citing works
Wright, J. H., Huang, L.-Y., Weaver, S., Archila, L. D., McAfee, M. S., Hirayama, A. V. V., Chapuis, A. G., Bleakley, M., Rongvaux, A., Turtle, C. J., et al. (2020) · Journal of Immunological Methods · doi:10.1016/j.jim.2020.112955 · Cited by 6 · see citing works
Wang, X.-Y., Zhang, W., Jia, Y., Wang, M., Yi, D., & Wang, T. (2020) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmaa105 · Cited by 6 · see citing works
Ali, A. M., Özdemirli, M., Hamilton, M. P., & Jain, M. D. (2026) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-026-01147-w · Cited by 7 · see citing works
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Schambach, A., Maetzig, T., & Baum, C. (2008) · CRC Press eBooks · doi:10.1201/9780849387999.pt1 · Cited by 5 · see citing works
Plugging synthetic DNA nanoparticles into the central dogma of life
Neyra, K., Desai, S., & Mathur, D. (2024) · Chemical Communications · doi:10.1039/d4cc04648j · Cited by 4 · see citing works
Obeid, M., Akkawi, R., Repudi, S., Singh, P. K., Abudiab, B., Jebara, T., Berent, A., Brennan, T., Weiss, Y., Shekh‐Ahmad, T., et al. (2026) · Molecular Therapy Advances · doi:10.1016/j.omta.2026.201791 · Cited by 4 · see citing works
Andrés‐Mateos, E., Kozlowski, C., Zhang, H., Fajardo, D., Xu, E., Navas‐Enamorado, I., Calabro, K. R., Rayaprolu, S., Havlik, L. P., Handy, T. E., et al. (2026) · Molecular Therapy · doi:10.1016/j.ymthe.2026.03.014 · Cited by 3 · see citing works
Adenovirus 5 Vectors Expressing SARS-CoV-2 Proteins
Bachus, S., Akkerman, N., Fulham, L., Graves, D., Stephanson, C., Memon, H., Miller, M. S., & Pelka, P. (2022) · mSphere · doi:10.1128/msphere.00998-21 · Cited by 3 · see citing works
Zhou, X., Liu, Q., Wang, D., Zhang, X., Emery, D. W., & Li, C. L. (2017) · Cytogenetic and Genome Research · doi:10.1159/000464315 · Cited by 3 · see citing works
Bauer, G., & Anderson, J. S. (2014) · SpringerBriefs in biochemistry and molecular biology · doi:10.1007/978-1-4939-0434-1_4 · Cited by 3 · see citing works
Goldman, C., Kareva, T., Sarrafha, L., Schuldt, B. R., Sahasrabudhe, A., Ahfeldt, T., & Blanchard, J. (2025) · iScience · doi:10.1016/j.isci.2025.112816 · Cited by 2 · see citing works
Humanized extracellular vesicles for efficient RNA delivery
Ma, X., Zhao, S. R., & Cepko, C. L. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2525726123 · Cited by 2 · see citing works
Meganck, R. M., Ogurlu, R., Liu, J., Møller-Tank, S., Tse, L. V., Blondel, L. O., Rosales, A., Hall, A. C., Vincent, H. A., Moorman, N. J., et al. (2024) · Journal of Virology · doi:10.1128/jvi.00095-24 · Cited by 2 · see citing works
Ma, J., Meyer, S., Olweus, J., Jin, C., & Yu, D. (2024) · Immuno-Oncology Technology · doi:10.1016/j.iotech.2024.101031 · Cited by 2 · see citing works
Dady, A., Davidson, L., Loyer, N., Rappich, S., Findlay, G. M., Sanders, T., Januschke, J., & Storey, K. G. (2025) · Development · doi:10.1242/dev.205082 · Cited by 2 · see citing works
Jäschke, N. M., & Büning, H. (2022) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2022.04.002 · Cited by 2 · see citing works
Müller, L., Milsom, M. D., & Williams, D. A. (2010) · Springer eBooks · doi:10.1007/978-1-4419-7656-7_6 · Cited by 2 · see citing works
Jones, A., Massey, S. E., Zhang, D., Deigin, Y., & Quay, S. C. (2022) · Applied Microbiology · doi:10.3390/applmicrobiol2040068 · Cited by 2 · see citing works
Retroviral Integration Target Site Selection
Ciuffi, A., & Bushman, F. D. (2011) · Wiley eBooks · doi:10.1002/9781118015377.ch5 · Cited by 2 · see citing works
Development of viral & non-viral episomal vectors for gene therapy applications
Kymäläinen, H. (2012) · OpenGrey (Institut de l'Information Scientifique et Technique) · Cited by 2 · see citing works
Pullarkat, S., Black, G., Bleakley, M., Buenrostro, D., Chapuis, A. G., Hirayama, A. V. V., Jaeger-Ruckstuhl, C. A., Kimble, E. L., Lee, B. M., Maloney, D. G., et al. (2024) · PLoS ONE · doi:10.1371/journal.pone.0303057 · Cited by 1 · see citing works
Enhancing human ACE2 expression in mouse models to improve COVID ‐19 research
Jiaoyang, S., Shaofei, C., Guangliang, H., Xiongzhi, Q., Haofeng, L., Rui, M., Grillari, J., Zheng‐Li, S., Jiekai, C., Meiqin, L., et al. (2024) · FEBS Open Bio · doi:10.1002/2211-5463.13934 · Cited by 1 · see citing works
Tsachaki, M., Peltret, M., Laplace, T. B., Vaxelaire-Hily, E., Mosbaoui, F., Aillerie, C., Schmid, A., Galea, A., Contarin, F., Duarte, L., et al. (2026) · New Biotechnology · doi:10.1016/j.nbt.2026.03.008 · Cited by 1 · see citing works
Structural basis of lipid-dependent allosteric gating mechanisms for PC1-PC2 ion channel
Chen, M., Wang, Z., Shi, Y., Huang, G., Morais, T. D. C., Pillai, A., Wang, Y., Mou, M. A., Jing, D., Fan, R., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-75084-8 · Cited by 1 · see citing works
Dady, A., Davidson, L., Loyer, N., Rappich, S., Findlay, G. M., Sanders, T., Januschke, J., & Storey, K. G. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.01.591467 · Cited by 1 · see citing works
Transcription, Translation, and the Control of Gene Expression in Mammalian Cells
Mullick, A., & Bernard Massie, B. (2010) · Encyclopedia of Industrial Biotechnology · doi:10.1002/9780470054581.eib565
PROTEASOME INHIBITION ENHANCES THE EFFECT OF BIKDD GENE THERAPY
Sun, Y. (2014) · Digital Commons-TMC (Texas Medical Center)
Strategies for Restoring Vision by Transducing a Channelrhodopsin Gene into Retinal Ganglion Cells
Tomita, H., & Sugano, E. (2017) · Cambridge University Press eBooks · doi:10.1017/9781107281875.028
The WPRE improves genetic engineering with site-specific nucleasesPreprint
Ong, J. M., Brown, C. R., Mendel, M. C., & Cost, G. J. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/126904
Foamy virus vector integration and application in gene therapy
Sweeney, N. P. (2015) · Spiral (Imperial College London) · doi:10.25560/50704
Digital Droplet PCR Method for the Quantification of AAV Transduction Efficiency in Murine Retina
Okan, I. C. T., Ahmadian, M., Tutuncu, Y., Altay, H. Y., & Ağca, C. (2021) · Journal of Visualized Experiments · doi:10.3791/63038
Jones, A., Massey, S. E., Zhang, D., Deigin, Y., & Quay, S. C. (2022) · Research Square · doi:10.21203/rs.3.rs-1836803/v1
Jones, A., Massey, S. E., Zhang, D., Deigin, Y., & Quay, S. C. (2022) · Research Square · doi:10.21203/rs.3.rs-1836803/v2
Goldman, C., Kareva, T., Sarrafha, L., Schuldt, B. R., Sahasrabudhe, A., Ahfeldt, T., & Blanchard, J. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4886465
Jin, H., Cho, Y. R., & Jung, Y. T. (2025) · Acta Virologica · doi:10.3389/av.2025.14262
de Silly, R. V., Seijo, B., Maillard, J., Reichenbach, P., & Irving, M. B. (2025) · NAR Molecular Medicine · doi:10.1093/narmme/ugaf030
NATO3 protects dopaminergic neurons in mouse in vivo and human in vitro Parkinson’s disease modelsPreprint
Valencia-Alarcón, E. P., Duret, L. C., Kobayashi, E., Cattaneo, O., Schneider, B. L., & Nagoshi, E. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.10.681573
Investigation of the effects of virus integration on host gene expression in mouse tumour samples
Osejindu, E. (2011) · Brunel University Research Archive (BURA) (Brunel University London)
Wright, J., Alberts, B. M., Quiles, M. L. M., Guarino, A., Chipchase, D., Clarkson, N. G., Mitrophanous, K. A., & Farley, D. C. (2025) · Molecular Therapy Advances · doi:10.1016/j.omta.2025.201654
AAV-TNNI3 rescues an experimental murine Tnni3 mutation resulting in thin filament mediated DCM
Bushway, P., Feng, W., Cruz, M. S., Maisel, S., Shathaya, A., Rao, P., Patel, U., Park, J., Chen, C., Tang, Z., et al. (2026) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2026.01.001
Coppens-Exandier, H., Mackanga, F., Darde, T., Bonhomme, C., Angenard, G., Leroyer, P., Ribault, C., Gicquel, T., Pelletier, R., Roshchina, F., et al. (2026) · Archives of Toxicology · doi:10.1007/s00204-026-04453-5
Highly Efficient Lentiviral Transduction of Human iPSC-Derived Microglia and MacrophagesPreprint
Goberdhan, S. C., Czubala, M. A., Thomas, S. E., Taylor, P. R., & Connor‐Robson, N. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.23.727402
Polymerizing laminins: Assembly, functions and disorders
Yurchenco, P. D. (2026) · Matrix Biology · doi:10.1016/j.matbio.2026.102031
- Authors
- Higashimoto, T., Urbinati, F., Perumbeti, A., Jiang, G., Zarzuela, A., Chang, L.-J., Kohn, D. B., & Malik, P.
- Affiliations
- University of Southern California (US)
- University of Florida (US)
- Corresponding author
- Malik, P
- Venue
- Gene Therapy
- Published
- 2007-06-28
- Volume
- 14
- Issue
- 17
- Pages
- 1298-1304
- ISSN
- 0969-7128 (ISSN-L)
- 1476-5462
- OpenAlex
- W1975554944
- Cited by
- 101
- References
- 34
- Citations by year
- 2026: 13 · 2025: 9 · 2024: 10 · 2023: 2 · 2022: 10 · 2021: 4 · 2020: 3 · 2019: 3 · 2018: 1 · 2017: 6 · 2016: 3 · 2015: 2 · 2014: 6 · 2013: 3 · 2012: 5
- FWCI
- 2.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gene Therapy (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5u54hl070595-05)
- National Heart, Lung, and Blood Institute (P01HL073104, U54-HL070595, R01-HL70135-01, R01HL070135)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Keywords
- read-through transcription, retroviral vectors, long terminal repeat, HIV-1 long terminal repeat, viral titer, transgene expression, polyadenylation signal
- MeSH terms
- Animals, Cell Line, Genetic Engineering, Genetic Vectors, Humans, Leukemia Virus, Murine, Retroviridae, RNA Processing, Post-Transcriptional, Transcription, Genetic, Transfection, Simian Immunodeficiency Virus, Gene Expression, Gene Expression Regulation, Viral, Reading Frames, Hepatitis B Virus, Woodchuck, Transgenes, Terminal Repeat Sequences, Regulatory Elements, Transcriptional
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