Genomic editing of the HIV-1 coreceptor CCR5 in adult hematopoietic stem and progenitor cells using zinc finger nucleases
Open accessAbstract
The HIV-1 coreceptor CCR5 is a validated target for HIV/AIDS therapy. The apparent elimination of HIV-1 in a patient treated with an allogeneic stem cell transplant homozygous for a naturally occurring CCR5 deletion mutation (CCR5(Δ32/Δ32)) supports the concept that a single dose of HIV-resistant hematopoietic stem cells can provide disease protection. Given the low frequency of naturally occurring CCR5(Δ32/Δ32) donors, we reasoned that engineered autologous CD34(+) hematopoietic stem/progenitor cells (HSPCs) could be used for AIDS therapy. We evaluated disruption of CCR5 gene expression in HSPCs isolated from granulocyte colony-stimulating factor (CSF)-mobilized adult blood using a recombinant adenoviral vector encoding a CCR5-specific pair of zinc finger nucleases (CCR5-ZFN). Our results demonstrate that CCR5-ZFN RNA and protein expression from the adenoviral vector is enhanced by pretreatment of HSPC with protein kinase C (PKC) activators resulting in >25% CCR5 gene disruption and that activation of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway is responsible for this activity. Importantly, using an optimized dose of PKC activator and adenoviral vector we could generate CCR5-modified HSPCs which engraft in a humanized mouse model (albeit at a reduced level) and support multilineage differentiation in vitro and in vivo. Together, these data establish the basis for improved approaches exploiting adenoviral vector delivery in the modification of HSPCs.
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?
Li and co-workers modified CCR5 at a ratio more than 25% in adult HSCs using adenoviral vector-delivered ZFN assisted with optimized dose of protein kinase C activator.
“Most recently, Li and co-workers modified CCR5 at a ratio more than 25% in adult HSCs (HSCs isolated from adult blood after mobilization with GMCSF) by using adenoviral vector-delivered ZFN, assisted with optimized dose of protein kinase C activator.”
From Newer Gene Editing Technologies toward HIV Gene Therapy (2013) · cites this paper as [46]
For CD34+ cells, ZFN-AD5 vector achieved >25% CCR5 disruption.
“For CD34+ cells, ZFN-AD5 vector also achieved >25% CCR5 disruption [46].”
From Newer Gene Editing Technologies toward HIV Gene Therapy (2013) · cites this paper as [46]
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
Long-Term Control of HIV by CCR5 Delta32/Delta32 Stem-Cell Transplantation
Hütter, G., Nowak, D., Mossner, M., Ganepola, S., Muessig, A., Allers, K., Schneider, T., Hofmann, J., Kücherer, C., Blau, O., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0802905 · Cited by 1,837 · see citing works
IFNα activates dormant haematopoietic stem cells in vivo
Essers, M. A. G., Offner, S., Blanco-Bose, W. E., Waibler, Z., Kalinke, U., Duchosal, M. A., & Trumpp, A. (2009) · Nature · doi:10.1038/nature07815 · Cited by 1,368 · see citing works
Humanized mice in translational biomedical research
Shultz, L. D., Ishikawa, F., & Greiner, D. L. (2007) · Nature reviews. Immunology · doi:10.1038/nri2017 · Cited by 1,281 · see citing works
Retinoblastoma protein recruits histone deacetylase to repress transcription
Brehm, A., Miska, E. A., McCance, D. J., Reid, J. L., Bannister, A. J., & Kouzarides, T. (1998) · Nature · doi:10.1038/35404 · Cited by 1,231 · see citing works
Estimated HIV Incidence in the United States, 2006–2009
Prejean, J., Song, R., Hernandez, A., Ziebell, R., Green, T., Walker, F., Lin, L. S., An, Q., Mermin, J., Lansky, A., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017502 · Cited by 1,071 · see citing works
Humanized mice in translational biomedical research
Shultz, L. (2007) · The Mouseion at the JAXlibrary (Jackson Laboratory) · Cited by 1,036 · see citing works
Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases
Perez, E. E., Wang, J., Miller, J. C., Jouvenot, Y., Kim, K. A., Liu, O., Wang, N., Lee, G., Bartsevich, V. V., Lee, Y.-L., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1410 · Cited by 999 · see citing works
Self-citationDevelopment of functional human blood and immune systems in NOD/SCID/IL2 receptor γ chainnull mice
Ishikawa, F., Yasukawa, M., Lyons, B. L., Yoshida, S., Miyamoto, T., Yoshimoto, G., Watanabe, T., Akashi, K., Shultz, L. D., & Harada, M. (2005) · Blood · doi:10.1182/blood-2005-02-0516 · Cited by 933 · see citing works
Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation
Allers, K., Hütter, G., Hofmann, J., Loddenkemper, C., Rieger, K., Thiel, E., & Schneider, T. (2011) · Blood · doi:10.1182/blood-2010-09-309591 · Cited by 681 · see citing works
Holt, N., Wang, J., Kim, K., Friedman, G., Wang, X., Taupin, V., Crooks, G. M., Kohn, D. B., Gregory, P. D., Holmes, M. C., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt.1663 · Cited by 677 · see citing works
Self-citationAn unbiased genome-wide analysis of zinc-finger nuclease specificity
Gabriel, R., Lombardo, A., Arens, A., Miller, J. C., Genovese, P., Kaeppel, C., Nowrouzi, A., Bartholomae, C. C., Wang, J., Friedman, G., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1948 · Cited by 526 · see citing works
Self-citationGene transfer in humans using a conditionally replicating lentiviral vector
Levine, B. L., Humeau, L. M. P. F., Boyer, J., MacGregor, R.-R., Rebello, T., Lü, X., Binder, G. K., Slepushkin, V., Lemiale, F., Mascola, J. R., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608138103 · Cited by 505 · see citing works
A Rapid and General Assay for Monitoring Endogenous Gene Modification
Guschin, D. Y., Waite, A. J., Katibah, G. E., Miller, J. C., Holmes, M. C., & Rebar, E. J. (2010) · Methods in molecular biology · doi:10.1007/978-1-60761-753-2_15 · Cited by 500 · see citing works
Self-citationBaltimore, D. (1988) · Nature · doi:10.1038/335395a0 · Cited by 422 · see citing works
Targeted gene knockout in mammalian cells by using engineered zinc-finger nucleases
Santiago, Y., Chan, E. M., Liu, P., Orlando, S., Zhang, L., Urnov, F. D., Holmes, M. C., Guschin, D. Y., Waite, A. J., Miller, J. C., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800940105 · Cited by 358 · see citing works
Self-citationPleiotrophin regulates the expansion and regeneration of hematopoietic stem cells
Himburg, H. A., Muramoto, G. G., Daher, P., Meadows, S. K., Russell, J. L., Doan, P. L., Chi, J., Salter, A. B., Lento, W. E., Reya, T., et al. (2010) · Nature Medicine · doi:10.1038/nm.2119 · Cited by 285 · see citing works
Simultaneous measurement of multiple active kinase states using polychromatic flow cytometry
Perez, O. D., & Nolan, G. P. (2002) · Nature Biotechnology · doi:10.1038/nbt0202-155 · Cited by 279 · see citing works
Phase 2 gene therapy trial of an anti-HIV ribozyme in autologous CD34+ cells
Mitsuyasu, R. T., Merigan, T. C., Carr, A. D., Zack, J. A., Winters, M. A., Workman, C., Bloch, M. T., Lalezari, J. P., Becker, S., Thornton, L., et al. (2009) · Nature Medicine · doi:10.1038/nm.1932 · Cited by 263 · see citing works
Fredericksen, B. L., Wei, B. L., Yao, J. Q., Luo, T., & García, J. V. (2002) · Journal of Virology · doi:10.1128/jvi.76.22.11440-11446.2002 · Cited by 211 · see citing works
Synthetic lethality: exploiting the addiction of cancer to DNA repair
Shaheen, M. F., Allen, C., Nickoloff, J. A., & Hromas, R. (2011) · Blood · doi:10.1182/blood-2011-01-313734 · Cited by 200 · see citing works
Durable remissions with autologous stem cell transplantation for high-risk HIV-associated lymphomas
Krishnan, A. Y., Molina, A., Zaia, J. A., Smith, D. D., Vasquez, D. S., Kogut, N. M., Falk, P., Rosenthal, J., Alvarnas, J., & Forman, S. J. (2004) · Blood · doi:10.1182/blood-2004-04-1532 · Cited by 188 · see citing works
Self-citationAttenuation of Zinc Finger Nuclease Toxicity by Small-Molecule Regulation of Protein Levels
Pruett‐Miller, S. M., Reading, D. W., Porter, S. N., & Porteus, M. H. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000376 · Cited by 135 · see citing works
Nilsson, M., Ljungberg, J., Richter, J., Kiefer, T., Magnusson, M., Lieber, A., Widegren, B., Karlsson, S., & Fan, X. (2004) · The Journal of Gene Medicine · doi:10.1002/jgm.543 · Cited by 129 · see citing works
Shayakhmetov, D. M., Li, Z.-Y., Ternovoi, V. V., Gaggar, A., Gharwan, H., & Lieber, A. (2003) · Journal of Virology · doi:10.1128/jvi.77.6.3712-3723.2003 · Cited by 123 · see citing works
Shiraishi, T., & Nielsen, P. E. (2006) · Nature Protocols · doi:10.1038/nprot.2006.92 · Cited by 116 · see citing works
Generation of a triple-gene knockout mammalian cell line using engineered zinc-finger nucleases
Liu, P., Chan, E. M., Cost, G. J., Zhang, L., Wang, J., Miller, J. C., Guschin, D. Y., Reik, A., Holmes, M. C., Mott, J. E., et al. (2010) · Biotechnology and Bioengineering · doi:10.1002/bit.22654 · Cited by 107 · see citing works
Self-citationAntineoplastic bryostatins are multipotential stimulators of human hematopoietic progenitor cells.
May, W. S., Sharkis, S. J., Esa, A. H., Gebbia, V., Kraft, A. S., Pettit, G. R., & Sensenbrenner, L. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.23.8483 · Cited by 102 · see citing works
Second messengers regulate endosomal acidification in Swiss 3T3 fibroblasts.
Zen, K., Biwersi, J., Periasamy, N., & Verkman, A. S. (1992) · The Journal of Cell Biology · doi:10.1083/jcb.119.1.99 · Cited by 88 · see citing works
Podsakoff, G. M., Engel, B. C., Carbonaro, D. A., Choi, C. Y. C., Smogorzewska, E. M., Bauer, G., Selander, D., Csik, S., Wilson, K., Betts, M. R., et al. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2005.02.024 · Cited by 81 · see citing works
Knaän‐Shanzer, S., van der Velde, I., Havenga, M. J. E., Lemckert, A. A. C., de Vries, A. A. F., & Valerio, D. (2001) · Human Gene Therapy · doi:10.1089/104303401753204562 · Cited by 70 · see citing works
Davis, T. A., Saini, A. A., Blair, P. J., Levine, B. L., Craighead, N., Harlan, D. M., June, C. H., & Lee, K. P. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.8.3689 · Cited by 70 · see citing works
Myklebust, J. H., Smeland, E. B., Josefsen, D., & Sioud, M. (2000) · Blood · doi:10.1182/blood.v95.2.510 · Cited by 61 · see citing works
Novel Cell and Gene Therapies for HIVPreprint
Hoxie, J. A., & June, C. H. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a007179 · Cited by 61 · see citing works
Pleiotrophin as a Possible New Target for Angiogenesis-Related Diseases and Cancer
Mikelis, C. M., Κουτσιούμπα, Μ., & Papadimitriou, Ε. (2007) · Recent Patents on Anti-Cancer Drug Discovery · doi:10.2174/157489207780832405 · Cited by 59 · see citing works
HIV-1 Nef-induced FasL induction and bystander killing requires p38 MAPK activation
Muthumani, K., Choo, A. Y., Hwang, D. S., Arumugam, P., Dayes, N. S., Harris, C. A., Green, D. R., Wadsworth, S. A., Siekierka, J. J., & Weiner, D. B. (2005) · Blood · doi:10.1182/blood-2005-03-0932 · Cited by 53 · see citing works
The protein kinase C (PKC) family of proteins in cytokine signaling in hematopoiesis
Redig, A. J., & Platanias, L. C. (2007) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2007.0007 · Cited by 51 · see citing works
Friebe, A., & Volk, H. (2008) · PubMed · doi:10.5858/132.11.1802 · Cited by 46 · see citing works
Role of HIV Vpr as a Regulator of Apoptosis and an Effector on Bystander Cells
Moon, H. S., & Yang, J.-S. (2006) · Molecules and Cells · doi:10.1016/s1016-8478(23)12897-4 · Cited by 46 · see citing works
Gschwend, J. E., Fair, W. R., & Powell, C. T. (2000) · PubMed · Cited by 43 · see citing works
Permeability characteristics of erythrocyte membrane to okadaic acid and calyculin A
Namboodiripad, A. N., & Jennings, M. L. (1996) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1996.270.2.c449 · Cited by 43 · see citing works
Zielske, S. P., & Gerson, S. L. (2003) · Molecular Therapy · doi:10.1016/s1525-0016(03)00005-4 · Cited by 41 · see citing works
Histone deacetylase inhibition modulates cell fate decisions during myeloid differentiation
Bartels, M., Geest, C. R., Bierings, M., Buitenhuis, M., & Coffer, P. J. (2010) · Haematologica · doi:10.3324/haematol.2009.008870 · Cited by 40 · see citing works
IFN-α wakes up sleeping hematopoietic stem cells
Passegue, E. A., & Ernst, P. (2009) · Nature Medicine · doi:10.1038/nm0609-612 · Cited by 39 · see citing works
Isern, E., Gustems, M., Messerle, M., Borst, E. M., Ghazal, P., & Angulo, A. (2010) · Journal of Virology · doi:10.1128/jvi.01713-10 · Cited by 38 · see citing works
Nilsson, M., Karlsson, S., & Fan, X. (2004) · Molecular Therapy · doi:10.1016/j.ymthe.2003.12.014 · Cited by 36 · see citing works
PRDM1 Is Required for Mantle Cell Lymphoma Response to Bortezomib
Desai, S., Maurin, M. M., Smith, M. A., Bolick, S. C. E., Dessureault, S., Tao, J., Sotomayor, E., & Wright, K. L. (2010) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-10-0131 · Cited by 31 · see citing works
Hegedűs, C., Lakatos, P., Oláh, G., Tóth, B. I., Gergely, S., Szabó, É., Bı́ró, T., Szabó, C., & Virág, L. (2008) · FEBS Letters · doi:10.1016/j.febslet.2008.04.023 · Cited by 24 · see citing works
Gschwend, J. E., Fair, W. R., & Powell, C. T. (2000) · Molecular Pharmacology · doi:10.1016/s0026-895x(24)23233-8 · Cited by 23 · see citing works
Inducible gene expression from multiple promoters by the tumor-promoting agent, PMA
LEBKOWSKI, J. S., McNally, M. A., OKARMA, T. B., & Lerch, L. B. (1987) · Nucleic Acids Research · doi:10.1093/nar/15.21.9043 · Cited by 18 · see citing works
Discovery of Novel Proteasome Inhibitors Using a High-Content Cell-Based Screening System
Lavelin, I., Beer, A., Kam, Z., Rotter, V., Oren, M., Navon, A., & Geiger, B. (2009) · PLoS ONE · doi:10.1371/journal.pone.0008503 · Cited by 17 · see citing works
Tran, C.-A., Torres-Coronado, M., Gardner, A. M., Gu, A., Vu, H., Rao, A., Cao, L., Ahmed, A. Y., & DiGiusto, D. L. (2012) · Stem Cells Translational Medicine · doi:10.5966/sctm.2011-0062 · Cited by 7 · see citing works
Self-citationBlaghen, M., Bouhalloui, A., Taleb, H., Idrissi, H., Talha, F. T., Talbi, M., & Fellat-Zarrouck, K. (1997) · Toxicon · doi:10.1016/s0041-0101(96)00199-7 · Cited by 5 · see citing works
Flagged first, then by citations
1 of the 53 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Dunbar, C. E., High, K. A., Joung, J. K., Kohn, D. B., Ozawa, K., & Sadelain, M. (2018) · Science · doi:10.1126/science.aan4672 · Cited by 1,410 · see citing works
Gene therapy returns to centre stage
Naldini, L. (2015) · Nature · doi:10.1038/nature15818 · Cited by 1,184 · see citing works
HIV infection: epidemiology, pathogenesis, treatment, and prevention
Maartens, G., Celum, C., & Lewin, S. R. (2014) · The Lancet · doi:10.1016/s0140-6736(14)60164-1 · Cited by 835 · see citing works
Genome-editing Technologies for Gene and Cell Therapy
Maeder, M. L., & Gersbach, C. A. (2016) · Molecular Therapy · doi:10.1038/mt.2016.10 · Cited by 722 · see citing works
Genome Engineering with Targetable Nucleases
Carroll, D. (2014) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060713-035418 · Cited by 541 · see citing works
RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection
Hu, W., Kaminski, R., Yang, F., Zhang, Y., Cosentino, L., Li, F., Luo, B., Alvarez-Carbonell, D., Garcia-Mesa, Y., Karn, J., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1405186111 · Cited by 527 · see citing works
Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT)
Cappellini, M. D., Cohen, A. R., Porter, J. B., Taher, A. T., & Viprakasit, V. (2014) · Cited by 400 · see citing works
Origins of Programmable Nucleases for Genome Engineering
Chandrasegaran, S., & Carroll, D. (2015) · Journal of Molecular Biology · doi:10.1016/j.jmb.2015.10.014 · Cited by 327 · see citing works
Ye, L., Wang, J., Beyer, A. I., Teque, F., Cradick, T. J., Qi, Z., Chang, J. C., Bao, G., Muench, M. O., Yu, J., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1407473111 · Cited by 320 · see citing works
Self-citationKang, X., He, W., Huang, Y., Qian, Y., Chen, Y., Gao, X., Sun, X., & Fan, Y. (2016) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-016-0710-8 · Cited by 263 · see citing works
Wang, J., Exline, C. M., DeClercq, J. J., Llewellyn, G. N., Hayward, S. B., Li, P. W.-L., Shivak, D. A., Surosky, R. T., Gregory, P. D., Holmes, M. C., et al. (2015) · Nature Biotechnology · doi:10.1038/nbt.3408 · Cited by 261 · see citing works
Self-citationXu, L., Yang, H., Gao, Y., Chen, Z., Xie, L., Liu, Y., Liu, Y., Wang, X., Li, H., Lai, W., et al. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.04.027 · Cited by 246 · see citing works
Hematopoietic Stem Cell Gene Therapy: Progress and Lessons Learned
Morgan, R. A., Gray, D., Lomova, A., & Kohn, D. B. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.10.010 · Cited by 243 · see citing works
Wang, W., Ye, C., Liu, J., Zhang, D., Kimata, J. T., & Zhou, P. (2014) · PLoS ONE · doi:10.1371/journal.pone.0115987 · Cited by 196 · see citing works
Liu, Z., Chen, S., Jin, X., Wang, Q., Yang, K., Li, C., Xiao, Q., Hou, P., Liu, S., Wu, S., et al. (2017) · Cell & Bioscience · doi:10.1186/s13578-017-0174-2 · Cited by 175 · see citing works
Didigu, C. A., Wilen, C. B., Wang, J., Duong, J., Secreto, A. J., Danet-Desnoyers, G. A., Riley, J. L., Gregory, P. D., June, C. H., Holmes, M. C., et al. (2013) · Blood · doi:10.1182/blood-2013-08-521229 · Cited by 159 · see citing works
Self-citationEngineered Viruses as Genome Editing Devices
Chen, X., & Gonçalves, M. A. F. V. (2015) · Molecular Therapy · doi:10.1038/mt.2015.164 · Cited by 151 · see citing works
Liu, J., Gaj, T., Patterson, J. T., Sirk, S. J., & Barbas, C. F. (2014) · PLoS ONE · doi:10.1371/journal.pone.0085755 · Cited by 147 · see citing works
Kang, H., Minder, P., Park, M. A., Mesquitta, W.-T., Torbett, B. E., & Slukvin, I. I. (2015) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2015.42 · Cited by 147 · see citing works
Current and future delivery systems for engineered nucleases: ZFN, TALEN and RGEN
Ain, Q. U., Chung, J. Y., & Kim, Y.-H. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.12.036 · Cited by 130 · see citing works
Therapeutic gene editing: delivery and regulatory perspectives
Shim, G., Kim, D., Park, G. T., Jin, H., Suh, S., & Oh, Y. (2017) · Acta Pharmacologica Sinica · doi:10.1038/aps.2017.2 · Cited by 121 · see citing works
Zhen, A., Peterson, C. W., Carrillo, M. A., Reddy, S. S., Youn, C., Lam, B. B., Chang, N. Y., Martin, H. A., Rick, J. W., Kim, J. S., et al. (2017) · PLoS Pathogens · doi:10.1371/journal.ppat.1006753 · Cited by 118 · see citing works
Genome Editing: A New Approach to Human Therapeutics
Porteus, M. H. (2015) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010814-124454 · Cited by 116 · see citing works
MicroRNAs and HIV-1 Infection: Antiviral Activities and Beyond
Swaminathan, G., Navas, S., & Martín‐García, J. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.12.017 · Cited by 115 · see citing works
DiGiusto, D. L., Cannon, P. M., Holmes, M. C., Li, L., Rao, A., Wang, J., Lee, G., Gregory, P. D., Kim, K. A., Hayward, S. B., et al. (2016) · Molecular Therapy — Methods & Clinical Development · doi:10.1038/mtm.2016.67 · Cited by 114 · see citing works
Self-citationTargeted genome editing by lentiviral protein transduction of zinc-finger and TAL-effector nucleases
Cai, Y., Bak, R. O., & Mikkelsen, J. G. (2014) · eLife · doi:10.7554/elife.01911 · Cited by 105 · see citing works
Ready for Repair? Gene Editing Enters the Clinic for the Treatment of Human Disease
Ernst, M. P. T., Broeders, M., Herrero-Hernandez, P., Oussoren, E., van der Ploeg, A. T., & Pijnappel, W. W. M. P. (2020) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2020.06.022 · Cited by 99 · see citing works
Richter, M., Saydaminova, K., Yumul, R., Krishnan, R., Liu, J., Nagy, E.-E., Singh, M., Izsvák, Z., Cattaneo, R., Uckert, W., et al. (2016) · Blood · doi:10.1182/blood-2016-04-711580 · Cited by 99 · see citing works
pEVL: A Linear Plasmid for Generating mRNA IVT Templates With Extended Encoded Poly(A) Sequences
Grier, A. E., Burleigh, S., Sahni, J., Clough, C. A., Cardot, V., Choe, D. C., Krutein, M. C., Rawlings, D. J., Jensen, M. C., Scharenberg, A. M., et al. (2016) · Molecular Therapy - Nucleic Acids · doi:10.1038/mtna.2016.21 · Cited by 95 · see citing works
RNA interference approaches for treatment of HIV-1 infection
Bobbin, M. L., Burnett, J., & Rossi, J. J. (2015) · Genome Medicine · doi:10.1186/s13073-015-0174-y · Cited by 93 · see citing works
State-of-the-art human gene therapy: part I. Gene delivery technologies.
Wang, D., & Gao, G. (2014) · PubMed · Cited by 85 · see citing works
Genome editing in crop improvement: Present scenario and future prospects
Miglani, G. S. (2017) · Journal of Crop Improvement · doi:10.1080/15427528.2017.1333192 · Cited by 84 · see citing works
Antiviral Goes Viral: Harnessing CRISPR/Cas9 to Combat Viruses in Humans
Soppe, J. A., & Lebbink, R. J. (2017) · Trends in Microbiology · doi:10.1016/j.tim.2017.04.005 · Cited by 77 · see citing works
The clinical potential of gene editing as a tool to engineer cell‐based therapeutics
Ashmore‐Harris, C., & Fruhwirth, G. O. (2020) · Clinical and Translational Medicine · doi:10.1186/s40169-020-0268-z · Cited by 76 · see citing works
Newer Gene Editing Technologies toward HIV Gene Therapy
Manjunath, N., Yi, G., Dang, Y., & Shankar, P. (2013) · Viruses · doi:10.3390/v5112748 · Cited by 77 · see citing works
CCR5Δ32 mutation and HIV infection: basis for curative HIV therapy
Allers, K., & Schneider, T. (2015) · Current Opinion in Virology · doi:10.1016/j.coviro.2015.06.007 · Cited by 77 · see citing works
The clinical applications of genome editing in HIV
Wang, C. X., & Cannon, P. M. (2016) · Blood · doi:10.1182/blood-2016-01-678144 · Cited by 72 · see citing works
Self-citationPeterson, C. W., Wang, J., Norman, K. K., Norgaard, Z. K., Humbert, O., Tse, C. K., Yan, J. J., Trimble, R. G., Shivak, D. A., Rebar, E. J., et al. (2016) · Blood · doi:10.1182/blood-2015-09-672337 · Cited by 67 · see citing works
Self-citationYin, C., Zhang, T., Li, F., Yang, F., Putatunda, R., Young, W., Khalili, K., Hu, W., & Zhang, Y. (2016) · AIDS · doi:10.1097/qad.0000000000001079 · Cited by 67 · see citing works
Kennedy, E. M., & Cullen, B. R. (2015) · Virology · doi:10.1016/j.virol.2015.02.024 · Cited by 64 · see citing works
Improved Cell-Penetrating Zinc-Finger Nuclease Proteins for Precision Genome Engineering
Liu, J., Gaj, T., Wallen, M. C., & Barbas, C. F. (2015) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2015.6 · Cited by 61 · see citing works
Stem-Cell-Based Gene Therapy for HIV Infection
Zhen, A., & Kitchen, S. G. (2013) · Viruses · doi:10.3390/v6010001 · Cited by 60 · see citing works
Which therapeutic strategy will achieve a cure for HIV-1?
Cillo, A. R., & Mellors, J. W. (2016) · Current Opinion in Virology · doi:10.1016/j.coviro.2016.02.001 · Cited by 59 · see citing works
Hematopoietic stem cell transplantation for HIV cure
Kuritzkes, D. R. (2016) · Journal of Clinical Investigation · doi:10.1172/jci80563 · Cited by 59 · see citing works
Saydaminova, K., Ye, X., Wang, H., Richter, M., Ho, M., Chen, H., Xu, N., Kim, J., Papapetrou, E. P., Holmes, M. C., et al. (2015) · Molecular Therapy — Methods & Clinical Development · doi:10.1038/mtm.2014.57 · Cited by 58 · see citing works
Self-citationRust, B. J., Kean, L. S., Colonna, L., Brandenstein, K. E., Poole, N. H., Obenza, W., Enstrom, M. R., Maldini, C. R., Ellis, G. I., Fennessey, C. M., et al. (2020) · Blood · doi:10.1182/blood.2020006372 · Cited by 58 · see citing works
RetractedCRISPR-Cas9: a promising tool for gene editing on induced pluripotent stem cells
Kim, E. J., Kang, K. H., & Ju, J. H. (2017) · The Korean Journal of Internal Medicine · doi:10.3904/kjim.2016.198 · Cited by 57 · see citing works
Gene Editing of Human Hematopoietic Stem and Progenitor Cells: Promise and Potential Hurdles
Yu, K., Natanson, H., & Dunbar, C. E. (2016) · Human Gene Therapy · doi:10.1089/hum.2016.107 · Cited by 54 · see citing works
Development of gene therapy for blood disorders: an update
Nienhuis, A. W. (2013) · Blood · doi:10.1182/blood-2013-04-453209 · Cited by 54 · see citing works
Adenovirus vectors in hematopoietic stem cell genome editing
Li, C., & Lieber, A. (2019) · FEBS Letters · doi:10.1002/1873-3468.13668 · Cited by 53 · see citing works
Sanz-Ramos, M., & Stoye, J. P. (2013) · Journal of General Virology · doi:10.1099/vir.0.058180-0 · Cited by 53 · see citing works
Yi, G., Choi, J. G., Bharaj, P., Abraham, S., Dang, Y., Kafri, T., Alozie, O. K., Manjunath, M. N., & Shankar, P. (2014) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2014.52 · Cited by 52 · see citing works
Knipping, F., Newby, G. A., Eide, C. R., McElroy, A. N., Nielsen, S. C., Smith, K. D., Fang, Y., Cornu, T. I., Costa, C., Gutiérrez-Guerrero, A., et al. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.10.026 · Cited by 51 · see citing works
Recent advances in genome editing of stem cells for drug discovery and therapeutic application
Lee, J., Bayarsaikhan, D., Bayarsaikhan, G., Kim, J., Schwarzbach, E., & Lee, B. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107501 · Cited by 47 · see citing works
Genome editing strategies: potential tools for eradicating HIV-1/AIDS
Khalili, K., Kaminski, R., Gordon, J., Cosentino, L., & Hu, W. (2015) · Journal of NeuroVirology · doi:10.1007/s13365-014-0308-9 · Cited by 48 · see citing works
Engineering and Application of Zinc Finger Proteins and TALEs for Biomedical Research
Kim, M., & Kini, A. G. (2017) · Molecules and Cells · doi:10.14348/molcells.2017.0139 · Cited by 45 · see citing works
Hofer, U., Henley, J. E., Exline, C. M., Mulhern, O., Lopez, E., & Cannon, P. M. (2013) · Journal of Infectious Diseases · doi:10.1093/infdis/jit382 · Cited by 43 · see citing works
Self-citationAdvancements in Developing Strategies for Sterilizing and Functional HIV Cures
Xu, W., Li, H., Wang, Q., Hua, C., Zhang, H., Li, W., Jiang, S., & Lu, L. (2017) · BioMed Research International · doi:10.1155/2017/6096134 · Cited by 44 · see citing works
Stem cell-based therapies for HIV/AIDS
Pernet, O., Yadav, S. S., & An, D. S. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2016.04.027 · Cited by 42 · see citing works
Integrating HDAd5/35++ Vectors as a New Platform for HSC Gene Therapy of Hemoglobinopathies
Li, C., Psatha, N., Wang, H., Singh, M., Samal, H. B., Zhang, W., Ehrhardt, A., Izsvák, Z., Papayannopoulou, T., & Lieber, A. (2018) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2018.02.004 · Cited by 42 · see citing works
Applications of TALENs and CRISPR/Cas9 in Human Cells and Their Potentials for Gene Therapy
Niu, J., Zhang, B., & Chen, H. (2014) · Molecular Biotechnology · doi:10.1007/s12033-014-9771-z · Cited by 40 · see citing works
Lee, B., Lozano, R. J., & Dunbar, C. E. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.09.001 · Cited by 38 · see citing works
Ling, C., Bhukhai, K., Yin, Z., Tan, M., Yöder, M. C., Leboulch, P., Payen, E., & Srivastava, A. (2016) · Scientific Reports · doi:10.1038/srep35495 · Cited by 39 · see citing works
Ex vivo expansion of hematopoietic stem cells: Finally transitioning from the lab to the clinic
Zimran, E., Papa, L., & Hoffman, R. (2021) · Blood Reviews · doi:10.1016/j.blre.2021.100853 · Cited by 38 · see citing works
Gene therapy and genome editing for primary immunodeficiency diseases
Zhang, Z., Thrasher, A. J., & Zhang, F. (2019) · Genes & Diseases · doi:10.1016/j.gendis.2019.07.007 · Cited by 37 · see citing works
Daniel-Moreno, A., Lamsfus‐Calle, A., Raju, J., Antony, J. S., Handgretinger, R., & Mezger, M. (2019) · Bone Marrow Transplantation · doi:10.1038/s41409-019-0510-8 · Cited by 37 · see citing works
Li, S., Holguin, L., & Burnett, J. C. (2022) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2022.01.012 · Cited by 35 · see citing works
The emerging role of RNA and DNA editing in cancer
Avesson, L., & Barry, G. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.03.001 · Cited by 35 · see citing works
CRISPR-Cas based targeting of host and viral genes as an antiviral strategy
Koujah, L., Shukla, D., & Naqvi, A. R. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.04.004 · Cited by 34 · see citing works
Tasca, F., Wang, Q., & Gonçalves, M. A. F. V. (2020) · Cells · doi:10.3390/cells9040953 · Cited by 34 · see citing works
Recent developments and clinical studies utilizing engineered zinc finger nuclease technology
Jo, Y.-I., Kim, S., & Ramakrishna, S. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-1956-5 · Cited by 36 · see citing works
Simple and Efficient Methods for Enrichment and Isolation of Endonuclease Modified Cells
Moriarity, B. S., Rahrmann, E. P., Beckmann, D. A., Conboy, C. B., Watson, A. L., Carlson, D. F., Olson, E. R., Hyland, K. A., Fahrenkrug, S. C., McIvor, R. S., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0096114 · Cited by 33 · see citing works
Agammaglobulinemia: causative mutations and their implications for novel therapies
Berglöf, A., Turunen, J. J., Gissberg, O., Bestas, B., Blomberg, K. E. M., & Smith, C. E. (2013) · Expert Review of Clinical Immunology · doi:10.1586/1744666x.2013.850030 · Cited by 32 · see citing works
Qi, C., Li, D., Jiang, X., Jia, X., Lu, L., Wang, Y., Sun, J., Shao, Y., & Wei, M. (2018) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2018.05.012 · Cited by 31 · see citing works
In Vivo Hematopoietic Stem Cell Transduction
Richter, M., Stone, D., Miao, C. H., Humbert, O., Kiem, H., Papayannopoulou, T., & Lieber, A. (2017) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2017.06.001 · Cited by 29 · see citing works
The therapeutic landscape of HIV-1 via genome editing
Kwarteng, A., Ahuno, S. T., & Kwakye-Nuako, G. (2017) · AIDS Research and Therapy · doi:10.1186/s12981-017-0157-8 · Cited by 29 · see citing works
Advance genome editing technologies in the treatment of human diseases: CRISPR therapy (Review)
Alagöz, M., & Kherad, N. (2020) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2020.4609 · Cited by 30 · see citing works
Historical Perspective on the Current Renaissance for Hematopoietic Stem Cell Gene Therapy
Kohn, D. B. (2017) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2017.06.006 · Cited by 27 · see citing works
Towards Improved shRNA and miRNA Reagents as Inhibitors of HIV1 Replication
Berkhout, B., & Liu, Y. P. (2014) · Future Microbiology · doi:10.2217/fmb.14.5 · Cited by 26 · see citing works
Liu, J., & Shui, S. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.11.014 · Cited by 24 · see citing works
Periwal, V. (2016) · Briefings in Bioinformatics · doi:10.1093/bib/bbw052 · Cited by 25 · see citing works
Gene Transfection for Stem Cell Therapy
Baek, K., Tu, C., Zoldan, J., & Suggs, L. J. (2016) · Current Stem Cell Reports · doi:10.1007/s40778-016-0029-5 · Cited by 23 · see citing works
Novel AIDS therapies based on gene editing
Khalili, K., White, M. K., & Jacobson, J. M. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2479-z · Cited by 23 · see citing works
Ye, C., Wang, W., Cheng, L., Li, G., Wen, M., Wang, Q., Zhang, Q., Li, D., Zhou, P., & Su, L. (2016) · Journal of Virology · doi:10.1128/jvi.01389-16 · Cited by 22 · see citing works
Knowledge From London and Berlin: Finding Threads to a Functional HIV Cure
Ding, J., Liu, Y., & Lai, Y. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.688747 · Cited by 21 · see citing works
Gene knockout in cellular immunotherapy: Application and limitations.
Zhang, X., Jin, X., Sun, R., Zhang, M., Lu, W.-Y., & Zhao, M.-F. (2022) · Cancer Letters · doi:10.1016/j.canlet.2022.215736 · Cited by 20 · see citing works
Post-transcriptional gene silencing, transcriptional gene silencing and human immunodeficiency virus
Méndez, C. (2015) · World Journal of Virology · doi:10.5501/wjv.v4.i3.219 · Cited by 22 · see citing works
Genome editing-based HIV therapies
Gu, W.-G. (2015) · Trends in biotechnology · doi:10.1016/j.tibtech.2014.12.006 · Cited by 20 · see citing works
Genome-edited adult stem cells: Next-generation advanced therapy medicinal products
Benabdellah, K., Sánchez-Hernández, S., Aguilar-González, A., Maldonado‐Pérez, N., Gutiérrez-Guerrero, A., Cortijo-Gutierréz, M., Ramos-Hernández, I., Tristán‐Manzano, M., Galindo‐Moreno, P., Herrera, C., et al. (2020) · Stem Cells Translational Medicine · doi:10.1002/sctm.19-0338 · Cited by 21 · see citing works
Spanevello, F., Calistri, A., Vecchio, C. D., Mantelli, B., Frasson, C., Basso, G., Palù, G., Cavazzana, M., & Parolin, C. (2016) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2016.24 · Cited by 19 · see citing works
Karuppusamy, K. V., Demosthenes, J. P., Venkatesan, V., Christopher, A. C., Babu, P., Azhagiri, M. K. K., Jacob, A., Ramalingam, V. V., Rangaraj, S., Mohankumar, K. M., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.792684 · Cited by 19 · see citing works
Lau, C., Zhu, H., Tay, J. C.-K., Li, Z., Tay, F. C., Chen, C., Tan, W.-K., Du, S., Sia, V.-K., Phang, R.-Z., et al. (2014) · Molecular Therapy — Methods & Clinical Development · doi:10.1038/mtm.2014.50 · Cited by 18 · see citing works
Zhao, N., Wang, G., Das, A. T., & Berkhout, B. (2017) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01486-17 · Cited by 18 · see citing works
Quynh, L. M., Dung, C. T., Thi, B., Huy, H. V., Loc, N. Q., Hoa, N. Q., Thach, P. T., Ánh, B. V., Thao, C. T., Nam, N. H., et al. (2018) · Journal of Immunoassay and Immunochemistry · doi:10.1080/15321819.2018.1488725 · Cited by 18 · see citing works
Manotham, K., Chattong, S., & Setpakdee, A. (2015) · Journal of Biomedical Science · doi:10.1186/s12929-015-0130-6 · Cited by 18 · see citing works
Genome editing technologies to fight infectious diseases
Trevisan, M., Palù, G., & Barzon, L. (2017) · Expert Review of Anti-infective Therapy · doi:10.1080/14787210.2017.1400379 · Cited by 18 · see citing works
Ibarra, G. S. R., Paul, B., Sather, B. D., Younan, P. M., Sommer, K., Kowalski, J. P., Hale, M. R., Stoddard, B. L., Jarjour, J., Astrakhan, A., et al. (2016) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2016.56 · Cited by 17 · see citing works
Gene Editing in Pluripotent Stem Cells and Their Derived Organoids
Zhou, H., Wang, Y., Liu, L., Li, Y., & Zheng, Y. (2021) · Stem Cells International · doi:10.1155/2021/8130828 · Cited by 17 · see citing works
HIV eradication—from Berlin to Boston
Cannon, P. M., Kohn, D. B., & Kiem, H. (2014) · Nature Biotechnology · doi:10.1038/nbt.2868 · Cited by 17 · see citing works
Self-citationGene editing in T cell therapy
Zhang, Y., Mu, W., & Wang, H. (2017) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2017.09.002 · Cited by 17 · see citing works
- Authors
- Li, L., Krymskaya, L., Wang, J., Henley, J., Rao, A., Cao, L.-F., Tran, C.-A., Torres-Coronado, M., Gardner, A., Gonzalez, N., Kim, K., Liu, P.-Q., Hofer, U., Lopez, E., Gregory, P. D., Liu, Q., Holmes, M. C., Cannon, P. M., Zaia, J. A., & DiGiusto, D. L.
- Affiliations
- City Of Hope National Medical Center (US)
- Sangamo BioSciences (United States) (US)
- University of Southern California (US)
- Corresponding author
- DiGiusto, David L
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2013-06
- Volume
- 21
- Issue
- 6
- Pages
- 1259-1269
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC3677314
- OpenAlex
- W2091634048
- Cited by
- 181
- References
- 53
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 7 · 2021: 11 · 2020: 10 · 2019: 8 · 2018: 11 · 2017: 24 · 2016: 33 · 2015: 28 · 2014: 24 · 2013: 14
- FWCI
- 21.90
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- California Institute for Regenerative Medicine (DR1-01490)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (133452)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Keywords
- zinc finger nucleases, hematopoietic stem and progenitor cells, genome editing, adenoviral vector, protein kinase C activation, MEK/ERK signaling, autologous stem cell therapy, humanized mice, multilineage differentiation, HIV/AIDS treatment
- MeSH terms
- Acquired Immunodeficiency Syndrome, Adenoviridae, Animals, Cell Differentiation, Cell Survival, Cells, Cultured, Disease Models, Animal, Endonucleases, Genetic Vectors, Hematopoietic Stem Cells, Humans, HIV-1, Granulocyte Colony-Stimulating Factor, Zinc Fingers, Apoptosis, Gene Deletion, Hematopoietic Stem Cell Transplantation, Gene Targeting, Antigens, CD34, Receptors, CCR5, Genomics, Extracellular Signal-Regulated MAP Kinases, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
