mRNA as gene therapeutic: How to control protein expression
Abstract
For many years, it was generally accepted that mRNA is too unstable to be efficiently used for gene therapy purposes. In the last decade, however, several research groups faced this challenge and not only proved the feasibility of mRNA-mediated transfection with surprising results regarding transfection efficiency and duration of protein expression, but also were able to demonstrate major advantages over the use of pDNA. These advantages will be the first issue discussed in this review, which first of all addresses the notions that mRNA does not need to cross the nuclear barrier to exert its biological activity and in addition lacks CpG motifs, which reduces its immunogenicity. Secondly, it provides insight in the (in)stability of the mRNA molecule, in how mRNA can be modified to increase its half-life and in the necessities of exogenously produced mRNA to be successfully used in transfection protocols. Furthermore, this review gives an in-depth overview of the different techniques and vehicles for intracellular mRNA delivery exploited by us and other groups, comprising electroporation, gene gun injection, lipo- and polyplexes. Finally, it covers recent literature describing specific applications for mRNA based gene delivery, showing that until now most attention has been paid to vaccination strategies. This review offers a comprehensive overview of current knowledge of the major theoretical as well as practical aspects of mRNA-mediated transfection, showing both its possibilities and its pitfalls and should therefore be useful for a diverse scientific audience.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Many of the obstacles to mRNA vaccine development have been surmounted, and recently there has been a revival in the use of nonamplifying mRNA vaccines for cancer, allergy, and gene therapy.
“However, many of the obstacles to mRNA vaccine development have been surmounted, and recently there has been a revival in the use of nonamplifying mRNA vaccines for cancer (6), allergy (7), and gene therapy (8).”
From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [8]
Cites
Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8
Heil, F., Hemmi, H., Hochrein, H., Ampenberger, F., Kirschning, C., Akira, S., Lipford, G., Wagner, H., & Bauer, S. (2004) · Science · doi:10.1126/science.1093620 · Cited by 3,947 · see citing works
Shaw, G. D., & Kamen, R. (1986) · Cell · doi:10.1016/0092-8674(86)90341-7 · Cited by 3,946 · see citing works
CpG motifs in bacterial DNA trigger direct B-cell activation
Krieg, A. M., Yi, A.-K., Matson, S., Waldschmidt, T. J., Bishop, G. A., Teasdale, R., Koretzky, G. A., & Klinman, D. M. (1995) · Nature · doi:10.1038/374546a0 · Cited by 3,508 · see citing works
Pelletier, J., & Sonenberg, N. (1988) · Nature · doi:10.1038/334320a0 · Cited by 1,953 · see citing works
Caput, D., Beutler, B., Hartog, K., Thayer, R. M., Brown-Shimer, S. L., & Cerami, A. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.6.1670 · Cited by 1,516 · see citing works
Cellular and Molecular Barriers to Gene Transfer by a Cationic Lipid
Zabner, J., Fasbender, A., Moninger, T., Poellinger, K. A., & Welsh, M. J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.32.18997 · Cited by 1,408 · see citing works
P bodies and the control of mRNA translation and degradation
Parker, R., & Sheth, U. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.02.011 · Cited by 1,335 · see citing works
mRNA stability in mammalian cells
Ross, J. (1995) · Microbiological Reviews · doi:10.1128/mr.59.3.423-450.1995 · Cited by 1,324 · see citing works
Regulating the fate of mRNA: the control of cellular iron metabolism
Klausner, R. D., Rouault, T. A., & Harford, J. B. (1993) · Cell · doi:10.1016/0092-8674(93)90046-s · Cited by 1,210 · see citing works
Brennan, C. M., & Steitz*, J. A. (2001) · Cellular and Molecular Life Sciences · doi:10.1007/pl00000854 · Cited by 1,095 · see citing works
mRNA is an endogenous ligand for toll-like receptor 3
Karikó, K., Ni, H., Capodici, J., Lamphier, M., & Weissman, D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m310175200 · Cited by 1,062 · see citing works
Immunotherapeutic uses of CpG oligodeoxynucleotides
Klinman, D. M. (2004) · Nature reviews. Immunology · doi:10.1038/nri1329 · Cited by 1,007 · see citing works
High efficiency transformation by direct microinjection of DNA into cultured mammalian cells
Capecchi, M. R. (1980) · Cell · doi:10.1016/0092-8674(80)90358-x · Cited by 1,000 · see citing works
Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo.
Boczkowski, D., Nair, S. K., Snyder, D., & Gilboa, E. (1996) · The Journal of experimental medicine · doi:10.1084/jem.184.2.465 · Cited by 915 · see citing works
Cationic liposome-mediated RNA transfection.
Malone, R. W., Felgner, P. L., & Verma, I. M. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.16.6077 · Cited by 911 · see citing works
The cap and poly(A) tail function synergistically to regulate mRNA translational efficiency.
Gallie, D. R. (1991) · Genes & Development · doi:10.1101/gad.5.11.2108 · Cited by 868 · see citing works
Paine, P. L., Moore, L. C., & Horowitz, S. B. (1975) · Nature · doi:10.1038/254109a0 · Cited by 824 · see citing works
Ballas, Z. K., Rasmussen, W. L., & KRIEG, A. M. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.157.5.1840 · Cited by 758 · see citing works
Zanta, M. A., Belguise-Valladier, P., & Behr, J. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.1.91 · Cited by 723 · see citing works
Lipid-based Nanoparticles for Nucleic Acid Delivery
Li, W., & Szoka, F. C. (2007) · Pharmaceutical Research · doi:10.1007/s11095-006-9180-5 · Cited by 642 · see citing works
In vivo and in vitro gene transfer to mammalian somatic cells by particle bombardment.
Yang, N., Burkholder, J. K., Roberts, B., Martinell, B. J., & McCabe, D. E. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.24.9568 · Cited by 600 · see citing works
Cationic lipids, lipoplexes and intracellular delivery of genes.
Wasungu, L., & Hoekstra, D. (2006) · Journal of Controlled Release · doi:10.1016/j.jconrel.2006.06.024 · Cited by 575 · see citing works
Heiser, A., Coleman, D., Dannull, J., Yancey, D., Maurice, M. A., Lallas, C. D., Dahm, P., Niedzwiecki, D., Gilboa, E., & Vieweg, J. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0214364 · Cited by 562 · see citing works
Cell cycle dependence of gene transfer by lipoplex, polyplex and recombinant adenovirus
Brunner, S., Sauer, T., Carotta, S., Cotten, M. L., Saltik, M., & Wagner, E. (2000) · Gene Therapy · doi:10.1038/sj.gt.3301102 · Cited by 534 · see citing works
DELIVERY OF SUBSTANCES INTO CELLS AND TISSUES USING A PARTICLE BOMBARDMENT PROCESS
Sanford, J. C., Klein, T. M., Wolf, E. D., et al. (1987) · Particulate Science And Technology · doi:10.1080/02726358708904533 · Cited by 488 · see citing works
Heiser, A., Coleman, D., Dannull, J., Yancey, D. R., Maurice, M. A., Lallas, C. D., Dahm, P., Niedzwiecki, D., Gilboa, E., & Vieweg, J. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14364 · Cited by 487 · see citing works
Induction of virus‐specific cytotoxic T lymphocytes <i>in vivo</i> by liposome‐entrapped mRNA
Martinon, F., Krishnan, S., Lenzen, G., Magné, R., Gomard, E., Guillet, J., Lévy, J., & Meulien, P. (1993) · European Journal of Immunology · doi:10.1002/eji.1830230749 · Cited by 473 · see citing works
Boyes, J., & Bird, A. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05055.x · Cited by 471 · see citing works
Van Tendeloo, V. F. I., Ponsaerts, P., Lardon, F., Nijs, G., Lenjou, M., Van Broeckhoven, C., Van Bockstaele, D. R., & Berneman, Z. N. (2001) · Blood · doi:10.1182/blood.v98.1.49 · Cited by 468 · see citing works
The Control of mRNA Decapping and P-Body Formation
Franks, T. M., & Lykke‐Andersen, J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.11.001 · Cited by 399 · see citing works
Weide, B., Pascolo, S., Scheel, B., Derhovanessian, E., Pflugfelder, A., Eigentler, T. K., Pawelec, G., Hoerr, I., Rammensee, H.-G., & Garbe, C. (2009) · Journal of Immunotherapy · doi:10.1097/cji.0b013e3181a00068 · Cited by 378 · see citing works
(1995) · PubMed · Cited by 330 · see citing works
Cheng, L., Ziegelhoffer, P. R., & Yang, N. S. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.10.4455 · Cited by 329 · see citing works
Cancer immunotherapy with mRNA‐transfected dendritic cells
Gilboa, E., & Vieweg, J. (2004) · Immunological Reviews · doi:10.1111/j.0105-2896.2004.00139.x · Cited by 314 · see citing works
An electron microscopy study into the mechanism of gene transfer with lipopolyamines.
Labat-Moleur, F., Steffan, A., Brisson, C., Perron, H., Feugeas, O., Furstenberger, P., Oberling, F., Brambilla, E. M., & Behr, J. (1996) · PubMed · Cited by 300 · see citing works
[Electrochemotherapy, a new antitumor treatment: first clinical trial].
Mir, L. M., Belehradek, M., Domenge, C., Orlowski, S., Poddevin, B., Belehradek, J., Schwaab, G., Luboinski, B., & Paoletti, C. (1991) · PubMed · Cited by 272 · see citing works
Dual function of the messenger RNA cap structure in poly(A)-tail-promoted translation in yeast
Preiß, T., & Hentze, M. W. (1998) · Nature · doi:10.1038/33192 · Cited by 270 · see citing works
DNA vector chemistry: The covalent attachment of signal peptides to plasmid DNA
Sebestyén, M. G., Ludtke, J. J., Bassik, M. C., Zhang, G., Budker, V. G., Lukhtanov, E. A., Hagstrom, J. E., & Wolff, J. A. (1998) · Nature Biotechnology · doi:10.1038/nbt0198-80 · Cited by 270 · see citing works
Plasmid DNA entry into postmitotic nuclei of primary rat myotubes.
Dowty, M. E., Williams, P., Zhang, G., Hagstrom, J. E., & Wolff, J. A. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.10.4572 · Cited by 270 · see citing works
Regulation of the meiotic cell cycle in oocytes
Nebreda, Á. R., & Ferby, I. (2000) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00150-2 · Cited by 258 · see citing works
The Role of the Poly(A) Sequence in Mammalian Messenger RN
Brawerman, G. (1981) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238109114634 · Cited by 252 · see citing works
Repetitive Elements in Mammalian Telomeres Suppress Bacterial DNA-Induced Immune Activation
Gürsel, İ., Gürsel, M., Yamada, H., Ishii, K. J., Takeshita, F., & Klinman, D. M. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.3.1393 · Cited by 240 · see citing works
Tousignant, J. D., Gates, A., Ingram, L., Johnson, C. L., Nietupski, J. B., Cheng, S. H., Eastman, S. J., & Scheule, R. K. (2000) · Human Gene Therapy · doi:10.1089/10430340050207984 · Cited by 237 · see citing works
Nuclear targeting peptide scaffolds for lipofection of nondividing mammalian cells
Subramanian, A., Ranganathan, P. N., & Diamond, S. L. (1999) · Nature Biotechnology · doi:10.1038/12860 · Cited by 233 · see citing works
Bettinger, T. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.18.3882 · Cited by 224 · see citing works
CpG-Depleted Plasmid DNA Vectors with Enhanced Safety and Long-Term Gene Expression in Vivo
Yew, N. S., Zhao, H., Przybylska, M., Wu, I., Tousignant, J. D., Scheule, R. K., & Cheng, S. H. (2002) · Molecular Therapy · doi:10.1006/mthe.2002.0598 · Cited by 221 · see citing works
Mitosis enhances transgene expression of plasmid delivered by cationic liposomes
Tseng, W., Haselton, F. R., & Giorgio, T. D. (1999) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(99)00039-1 · Cited by 221 · see citing works
Yew, N. S., Zhao, H., Wu, I., Song, A., Tousignant, J. D., Przybylska, M., & Cheng, S. H. (2000) · Molecular Therapy · doi:10.1006/mthe.2000.0036 · Cited by 221 · see citing works
DNA methylation and autoimmune disease
Richardson, B. (2003) · Clinical Immunology · doi:10.1016/s1521-6616(03)00206-7 · Cited by 221 · see citing works
A nuclear localization signal can enhance both the nuclear transport and expression of 1 kb DNA
Ludtke, J. J., Zhang, G., Sebestyén, M. G., & Wolff, J. A. (1999) · Journal of Cell Science · doi:10.1242/jcs.112.12.2033 · Cited by 220 · see citing works
Renbaum, P., Abrahamove, D., Fainsod, A., Wilson, G. G., Rottem, S., & Razin, A. (1990) · Nucleic Acids Research · doi:10.1093/nar/18.5.1145 · Cited by 217 · see citing works
The Use of TLR7 and TLR8 Ligands for the Enhancement of Cancer Immunotherapy
Smits, E., Ponsaerts, P., Berneman, Z. N., & Tendeloo, V. F. V. (2008) · The Oncologist · doi:10.1634/theoncologist.2008-0097 · Cited by 216 · see citing works
Noncytopathic Sindbis virus RNA vectors for heterologous gene expression
Agapov, E. V., Frolov, I. V., Lindenbach, B. D., Prágai, B. M., Schlesinger, S., & Rice, C. M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.22.12989 · Cited by 214 · see citing works
Yew, N. S., Wang, K. X., Przybylska, M., Bagley, R. G., Stedman, M. R., Marshall, J., Scheule, R., & Cheng, S. H. (1999) · Human Gene Therapy · doi:10.1089/10430349950019011 · Cited by 202 · see citing works
Scheel, B., Teufel, R., Probst, J., Carralot, J., Geginat, J., Radsak, M. P., Jarrossay, D., Wagner, H., Jung, G., Rammensee, H., et al. (2005) · European Journal of Immunology · doi:10.1002/eji.200425656 · Cited by 198 · see citing works
Efficacy of a peptide-based gene delivery system depends on mitotic activity.
Wilke, M., Fortunati, E., van den Broek, M., Hoogeveen, A. T., & Scholte, B. J. (1996) · PubMed · Cited by 195 · see citing works
Activation of target-tissue immune-recognition molecules by double-stranded polynucleotides
Suzuki, K., Mori, A., Ishii, K. J., Saito, J., Singer, D. S., Klinman, D. M., Krause, P. R., & Kohn, L. D. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.5.2285 · Cited by 189 · see citing works
Bonehill, A., Tuyaerts, S., Nuffel, A. M. T. V., Heirman, C., Bos, T. J., Fostier, K., Neyns, B., & Thielemans, K. (2008) · Molecular Therapy · doi:10.1038/mt.2008.77 · Cited by 185 · see citing works
Weissman, D., Ni, H., Scales, D. A., Dude, A., Capodici, J., McGibney, K., Abdool, A. J., Isaacs, S. N., Cannon, G., & Karikó, K. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.8.4710 · Cited by 178 · see citing works
Freimark, B. D., Blezinger, H. P., Florack, V. J., Nordstrom, J. L., Long, S. D., Deshpande, D., Nochumson, S., & Petrak, K. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.9.4580 · Cited by 178 · see citing works
The Molecular Basis for the Lack of Immunostimulatory Activity of Vertebrate DNA
Stacey, K. J., Young, G. R., Clark, F., Sester, D. P., Roberts, T. L., Naik, S. H., Sweet, M. J., & Hume, D. A. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.7.3614 · Cited by 174 · see citing works
Bonehill, A., Nuffel, A. M. T. V., Corthals, J., Tuyaerts, S., Heirman, C., François, V., Colau, D., van der Bruggen, P., Neyns, B., & Thielemans, K. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-2982 · Cited by 167 · see citing works
Mockey, M., Gonçalves, C., Dupuy, F. P., Lemoine, F. M., Pichon, C., & Midoux, P. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.12.105 · Cited by 165 · see citing works
Lipid-mediated delivery of RNA is more efficient than delivery of DNA in non-dividing cells
Zou, S., Scarfo, K. A., Nantz, M. H., & Hecker, J. G. (2010) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2010.01.019 · Cited by 161 · see citing works
Fasbender, A., Zabner, J., Zeiher, B. G., & Welsh, M. J. (1997) · Gene Therapy · doi:10.1038/sj.gt.3300524 · Cited by 160 · see citing works
Cap-Poly(A) Synergy in Mammalian Cell-free Extracts
Michel, Y. M., Poncet, D., Pirón, M., Kean, K. M., & Borman, A. M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004304200 · Cited by 159 · see citing works
Segal, B. M., Chang, J. T., & Shevach, E. M. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.11.5683 · Cited by 153 · see citing works
Qiu, P., Ziegelhoffer, P. R., Sun, J., & Yang, N. S. (1996) · PubMed · Cited by 150 · see citing works
Polarization of immunity induced by direct injection of naked sequence-stabilized mRNA vaccines
Carralot, J.-P., Probst, J., Hoerr, I., Scheel, B., Teufel, R., Jung, G., Rammensee, H.-G., & Pascolo, S. (2004) · Cellular and Molecular Life Sciences CMLS · doi:10.1007/s00018-004-4255-0 · Cited by 149 · see citing works
Reverse 5' caps in RNAs made in vitro by phage RNA polymerases.
Pasquinelli, A. E., Dahlberg, J. E., & Lund, E. (1995) · PubMed · Cited by 148 · see citing works
Sæbøe‐Larssen, S., Fossberg, E., & Gaudernack, G. (2002) · Journal of Immunological Methods · doi:10.1016/s0022-1759(01)00506-3 · Cited by 140 · see citing works
Critical assessment of the nuclear import of plasmid during cationic lipid-mediated gene transfer
Escriou, V., Carri�re, M., Bussone, F., Wils, P., & Scherman, D. (2001) · The Journal of Gene Medicine · doi:10.1002/jgm.174 · Cited by 136 · see citing works
mRNA transfection of cervical carcinoma and mesenchymal stem cells mediated by cationic carriers
Rejman, J., Tavernier, G., Bavarsad, N., Demeester, J., & Smedt, S. C. D. (2010) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.07.124 · Cited by 133 · see citing works
Self-citationPoly(A)-tail-promoted translation in yeast: Implications for translational control
PREISS, T., MUCKENTHALER, M., & HENTZE, M. W. (1998) · RNA · doi:10.1017/s1355838298980669 · Cited by 123 · see citing works
Chan, C. K., & Jans, D. A. (1999) · Human Gene Therapy · doi:10.1089/10430349950017699 · Cited by 121 · see citing works
Dannull, J., Nair, S. K., Su, Z. Z., Boczkowski, D., DeBeck, C., Yang, B. K., Gilboa, E., & Vieweg, J. (2004) · Blood · doi:10.1182/blood-2004-10-3944 · Cited by 120 · see citing works
Ciolina, C., Byk, G., Blanche, F., Thuillier, V., Scherman, D., & Wils, P. (1998) · Bioconjugate Chemistry · doi:10.1021/bc980061a · Cited by 117 · see citing works
Mu, L., Kyte, J. A., Kvalheim, G., Aamdal, S., Dueland, S., Hauser, M., Hammerstad, H., Wæhre, H., Raabe, N. K., & Gaudernack, G. (2005) · British Journal of Cancer · doi:10.1038/sj.bjc.6602761 · Cited by 115 · see citing works
Cancer immunotherapy using RNA-loaded dendritic cells
Ponsaerts, P., Tendeloo, V. F. V., & Berneman, Z. N. (2003) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.2003.02286.x · Cited by 114 · see citing works
Hess, P. R., Boczkowski, D., Nair, S. K., Snyder, D. J., & Gilboa, E. (2005) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-005-0064-z · Cited by 113 · see citing works
Nuclear Localization Signal Peptides Enhance Cationic Liposome-Mediated Gene Therapy
Aronsohn, A. I., & Hughes, J. A. (1998) · Journal of drug targeting · doi:10.3109/10611869808995871 · Cited by 113 · see citing works
Bacterial DNA activates human neutrophils by a CpG‐independent pathway
Trevani, A. S., Chorny, A., Salamone, G. V., Vermeulen, M. E., Gamberale, R., Schettini, J. L., Raiden, S., & Geffner, J. R. (2003) · European Journal of Immunology · doi:10.1002/eji.200324334 · Cited by 105 · see citing works
Schwartz, B., Ivanov, M. A., Pitard, B., Escriou, V., Rangara, R., Byk, G., Wils, P., Crouzet, J., & Scherman, D. (1999) · Gene Therapy · doi:10.1038/sj.gt.3300795 · Cited by 101 · see citing works
Control of mRNA stability in eukaryotes
Newbury, S. F. (2005) · Biochemical Society Transactions · doi:10.1042/bst20060030 · Cited by 96 · see citing works
Collas, P., Husebye, H., & Aleström, P. (1996) · Transgenic Research · doi:10.1007/bf01980210 · Cited by 91 · see citing works
Control of mRNA stability in eukaryotes
Newbury, S. F. (2006) · Biochemical Society Transactions · doi:10.1042/bst0340030 · Cited by 91 · see citing works
Lu, D., Benjamin, R., Kim, M., Conry, R. M., & Curiel, D. (1994) · PubMed · Cited by 89 · see citing works
Immuno-gene therapy of cancer with tumour-mRNA transfected dendritic cells
Kyte, J. A., & Gaudernack, G. (2006) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-006-0161-7 · Cited by 89 · see citing works
Folding at the rhythm of the rare codon beat
Marı́n, M. (2008) · Biotechnology Journal · doi:10.1002/biot.200800089 · Cited by 87 · see citing works
Sendai virus vectors as an emerging negative‐strand RNA viral vector system
Bitzer, M., Armeanu, S., Lauer, U. M., & Neubert, W. J. (2003) · The Journal of Gene Medicine · doi:10.1002/jgm.426 · Cited by 85 · see citing works
Molecular mechanisms of meiotic maturation and arrest in fish and amphibian oocytes
Yamashita, M. (1998) · Seminars in Cell and Developmental Biology · doi:10.1006/scdb.1998.0251 · Cited by 83 · see citing works
Immunize and disappear—Safety-optimized mRNA vaccination with a panel of 29 allergens
Roesler, E., Weiss, R., Weinberger, E. E., Fruehwirth, A., Stoecklinger, A., Mostböck, S., Ferreira, F., Thalhamer, J., & Scheiblhofer, S. (2009) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.06.036 · Cited by 82 · see citing works
Bontkes, H. J., Kramer, D., Ruizendaal, J. J., Taanman-Kueter, E. W., Tendeloo, V. F. V., Meijer, C. J. L. M., & Hooijberg, E. (2006) · Gene Therapy · doi:10.1038/sj.gt.3302874 · Cited by 80 · see citing works
A role for Toll in autoimmunity
Krieg, A. Μ. (2002) · Nature Immunology · doi:10.1038/ni0502-423 · Cited by 79 · see citing works
Tachibana, R. (2001) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(01)00211-3 · Cited by 71 · see citing works
Zohra, F. T., Chowdhury, E. H., Tada, S., Hoshiba, T., & Akaike, T. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.04.059 · Cited by 71 · see citing works
Mirzayans, R., Aubin, R. A., & Paterson, M. C. (1992) · Mutation Research Letters · doi:10.1016/0165-7992(92)90045-j · Cited by 69 · see citing works
RNA-based gene transfer for adult stem cells and T cells
Smits, E., Ponsaerts, P., Lenjou, M., Nijs, G., van Bockstaele, D. V., Berneman, Z., & Tendeloo, V. V. (2004) · Leukemia · doi:10.1038/sj.leu.2403463 · Cited by 67 · see citing works
Anderson, D. M., Hall, L. L., Ayyalapu, A. R., Irion, V. R., Nantz, M. H., & Hecker, J. G. (2003) · Human Gene Therapy · doi:10.1089/10430340360535751 · Cited by 66 · see citing works
Zhang, W., He, L., Yuan, Z., et al. (1999) · Human Gene Therapy · doi:10.1089/10430349950018148 · Cited by 64 · see citing works
Chimeric Receptor mRNA Transfection as a Tool to Generate Antineoplastic Lymphocytes
Rabinovich, P., Komarovskaya, M., Wrzesinski, S. H., Alderman, J. L., Budak-Alpdogan, T., Karpikov, A., Guo, H., Flavell, R., Cheung, N.-K. V., Weissman, S., et al. (2008) · Human Gene Therapy · doi:10.1089/hum.2008.068 · Cited by 62 · see citing works
Kyte, J. A., Kvalheim, G., Aamdal, S., et al. (2005) · Cancer Gene Therapy · doi:10.1038/sj.cgt.7700837 · Cited by 61 · see citing works
Kobayashi, T., Yamanaka, R., Homma, J., et al. (2003) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-003-0408-5 · Cited by 61 · see citing works
Ni, H., Capodici, J., Cannon, G., Communi, D., Boeynaems, J., Karikó, K., & Weissman, D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110729200 · Cited by 60 · see citing works
Enhanced Dendritic Cell Antigen Presentation in RNA-Based Immunotherapy
Kalady, M. F., Onaitis, M. W., Padilla, K. M., Emani, S., Tyler, D. S., & Pruitt, S. K. (2002) · Journal of Surgical Research · doi:10.1006/jsre.2002.6435 · Cited by 59 · see citing works
High performance mRNA transfection through carbonate apatite–cationic liposome conjugates
Zohra, F. T., Chowdhury, E. H., & Akaike, T. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2009.02.050 · Cited by 58 · see citing works
Optimized transfection of mRNA transcribed from a d(A/T)100 tail-containing vector
Elango, N., Elango, S., Shivshankar, P., & Katz, M. S. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.03.067 · Cited by 57 · see citing works
Scheper, W., Meinsma, D., Holthuizen, P. E., et al. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.1.235 · Cited by 57 · see citing works
Intracellular fate and nuclear targeting of plasmid DNA
Neves, C., Escriou, V., Byk, G., Scherman, D., & Wils, P. (1999) · Cell Biology and Toxicology · doi:10.1023/a:1007693805849 · Cited by 56 · see citing works
Turnover and Translation of in Vitro Synthesized Messenger RNAs in Transfected, Normal Cells
Rajagopalan, L. E., & Malter, J. S. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.33.19871 · Cited by 56 · see citing works
Bontkes, H. J., Kramer, D., Ruizendaal, J. J., Meijer, C. J. L. M., & Hooijberg, E. (2008) · Clinical Immunology · doi:10.1016/j.clim.2008.02.001 · Cited by 55 · see citing works
Hecker, J. G., Hall, L. L., & Irion, V. R. (2001) · Molecular Therapy · doi:10.1006/mthe.2001.0272 · Cited by 52 · see citing works
Yoshida, Y., Kobayashi, E., Endo, H., et al. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6682 · Cited by 51 · see citing works
Borman, A. M., Michel, Y. M., Malnou, C. E., & Kean, K. M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205065200 · Cited by 50 · see citing works
Synergy between CpG- or non-CpG DNA and specific antigen for B cell activation
Wang, Y. (2003) · International Immunology · doi:10.1093/intimm/dxg020 · Cited by 49 · see citing works
Strenkowska, M., Kowalska, J., Łukaszewicz, M., Zuberek, J., Su, W., Rhoads, R. E., Darżynkiewicz, E., & Jemielity, J. (2010) · New Journal of Chemistry · doi:10.1039/b9nj00644c · Cited by 42 · see citing works
Enhancement of MSH receptor- and GAL4-mediated gene transfer by switching the nuclear import pathway
Chan, C.-K., & Jans, D. A. (2001) · Gene Therapy · doi:10.1038/sj.gt.3301366 · Cited by 39 · see citing works
Transgene expression of transfected supercoiled plasmid DNA concatemers in mammalian cells
Maucksch, C., Bohla, A., Hoffmann, F., et al. (2009) · The Journal of Gene Medicine · doi:10.1002/jgm.1310 · Cited by 39 · see citing works
Electroporation-mediated gene therapy
Isaka, Y., & Imai, E. (2007) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.4.5.561 · Cited by 39 · see citing works
Collas, P., & Aleström, P. (1997) · PubMed · Cited by 39 · see citing works
Blomberg, P., Eskandarpour, M., Song, X., et al. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)02486-5 · Cited by 37 · see citing works
DNA Sequences in Cationic Lipid:pDNA-Mediated Systemic Toxicities
Tousignant, J. D., Zhao, H., Yew, N. S., Cheng, S. H., Eastman, S. J., & Scheule, R. K. (2003) · Human Gene Therapy · doi:10.1089/10430340360535760 · Cited by 35 · see citing works
Amano, T., Kajiwara, K., Yoshikawa, K., Morioka, J., Nomura, S., Fujisawa, H., Kato, S., Fujii, M., Fukui, M., Hinoda, Y., et al. (2007) · Journal of neurosurgery · doi:10.3171/jns.2007.106.4.638 · Cited by 33 · see citing works
Interaction of Poliovirus-Specific RNAs with HeLa Cells and E. coli
Koch, G. (1973) · Modern aspects of electrochemistry · doi:10.1007/978-3-642-65772-6_4 · Cited by 32 · see citing works
Efficient expression of miniprep plasmid DNA after needle micro-injection into somatic cells.
Am, T., & As, A. (1993) · PubMed · Cited by 30 · see citing works
Vaccine therapy with dendritic cells transfected with Il13ra2 mRNA for glioma in mice
Saka, M., Amano, T., Kajiwara, K., et al. (2009) · Journal of neurosurgery · doi:10.3171/2009.9.jns09708 · Cited by 27 · see citing works
Jarnjak-Jankovic, S., Pettersen, R. D., Sæbøe‐Larssen, S., Wesenberg, F., & Gaudernack, G. (2005) · BMC Cancer · doi:10.1186/1471-2407-5-20 · Cited by 27 · see citing works
Komura, J., Okada, T., & Ono, T. (1995) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/0167-4781(94)00180-b · Cited by 27 · see citing works
Yu, H. B., Babiuk, L. A., & den Hurk, S. V. D. L. (2006) · Vaccine · doi:10.1016/j.vaccine.2006.11.046 · Cited by 27 · see citing works
Transferrin-Lipoplexes with Protamine-Condensed DNA for Serum-Resistant Gene Delivery
de Ilarduya, C. T., Arangoa, M. A., & Düzgüneş, N. (2003) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(03)73022-5 · Cited by 26 · see citing works
Naka, T., Iwahashi, M., Nakamura, M., Ojima, T., Nakamori, M., Ueda, K., Katsuda, M., Miyazawa, M., Ishida, K., & Yamaue, H. (2008) · Cancer Science · doi:10.1111/j.1349-7006.2007.00698.x · Cited by 26 · see citing works
Drastic effect of nanoapatite particles on liposome-mediated mRNA delivery to mammalian cells
Zohra, F. T., Chowdhury, E. H., Nagaoka, M., & Akaike, T. (2005) · Analytical Biochemistry · doi:10.1016/j.ab.2005.06.031 · Cited by 26 · see citing works
In‐vivo particle mediated delivery of mRNA to mammalian tissues: ballistic and biologic effects
Sohn, R. L., Murray, M. T., Schwarz, K., Nyitray, J., Purray, P., Franko, A. P., Palmer, K. C., Diebel, L. N., & Dulchavsky, S. A. (2001) · Wound Repair and Regeneration · doi:10.1046/j.1524-475x.2001.00287.x · Cited by 25 · see citing works
Double long‐chain amidine liposome‐mediated self replicating DNA transfection
Ouahabi, A., Pector, V., FUKS, R., et al. (1996) · FEBS Letters · doi:10.1016/0014-5793(96)00038-5 · Cited by 25 · see citing works
RNA as a tumor vaccine: a review of the literature
Saenz-Badillos, J., Amin, S., & Granstein, R. D. (2001) · Experimental Dermatology · doi:10.1034/j.1600-0625.2001.010003143.x · Cited by 24 · see citing works
In Vivo and In Vitro Analysis of Poly(A) Length Effects on mRNA Translation
Peng, J., Murray, E. L., & Schoenberg, D. R. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-033-1_15 · Cited by 23 · see citing works
Arenal, A., Pimentel, R., Garcı́a, C., et al. (2004) · Gene · doi:10.1016/j.gene.2004.04.007 · Cited by 23 · see citing works
Introduction: Meiotic maturation and arrest in animal oocytes
Sagata, N. (1998) · Seminars in Cell and Developmental Biology · doi:10.1006/scdb.1998.0247 · Cited by 20 · see citing works
Zhang, H., Zhang, L., Ren, J., Fan, L., Si, X., & Liu, W. (2006) · Cellular Immunology · doi:10.1016/j.cellimm.2006.05.004 · Cited by 19 · see citing works
Jemielity, J., Stȩpiński, J., Jaremko, M., Haber, D., Stolarski, R., Rhoads, R. E., & Darżynkiewicz, E. (2003) · Nucleosides Nucleotides & Nucleic Acids · doi:10.1081/ncn-120022611 · Cited by 19 · see citing works
van der Aa, M., Koning, G. A., van der Gugten, J., et al. (2005) · PubMed · Cited by 14 · see citing works
Enzymatic Synthesis of Ribonucleic Acid
Ochoa, S. (1961) · Springer eBooks · doi:10.1007/978-3-642-92819-2_31 · Cited by 10 · see citing works
Dell, K., Klein, C., & Gissmann, L. (2008) · Antiviral Therapy · doi:10.1177/135965350801300409 · Cited by 8 · see citing works
Rasmussen, A. B., Zocca, M.-B., Bonefeld, C. M., et al. (2004) · Scandinavian Journal of Immunology · doi:10.1111/j.0300-9475.2004.01374.x · Cited by 5 · see citing works
Truncated TERT mRNA transfected dendritic cells evoke TERT specific antitumor response in vivo.
Qiu, J., Lil, G.-W., Sui, Y.-F., et al. (2007) · PubMed · Cited by 5 · see citing works
Zarei, S., Arrighi, J.-F., Ongaro, G., et al. (2003) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2003.12492.x · Cited by 4 · see citing works
Hoerr, I. (2000) · doi:10.1002/1521-4141(200001)30:1
Flagged first, then by citations
Cited by
Sorted by citations
Block copolymer micelles in nanomedicine applications
Cabral, H., Miyata, K., Osada, K., & Kataoka, K. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00199 · Cited by 1,309 · see citing works
Nonviral delivery of self-amplifying RNA vaccines
Geall, A. J., Verma, A., Otten, G. R., Shaw, C. A., Hekele, A., Banerjee, K., Cu, Y., Beard, C. W., Brito, L. A., Krucker, T., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1209367109 · Cited by 675 · see citing works
Advances in the delivery of RNA therapeutics: from concept to clinical reality
Kaczmarek, J. C., Kowalski, P. S., & Anderson, D. G. (2017) · Genome Medicine · doi:10.1186/s13073-017-0450-0 · Cited by 656 · see citing works
Opportunities and Challenges in the Delivery of mRNA-Based Vaccines
Wadhwa, A., Aljabbari, A., Lokras, A., Foged, C., & Thakur, A. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12020102 · Cited by 584 · see citing works
Nanotechnologies in delivery of mRNA therapeutics using nonviral vector-based delivery systems
Guan, S., & Rosenecker, J. (2017) · Gene Therapy · doi:10.1038/gt.2017.5 · Cited by 389 · see citing works
McKinlay, C. J., Vargas, J. R., Blake, T. R., Hardy, J. W., Kanada, M., Contag, C. H., Wender, P. A., & Waymouth, R. M. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1614193114 · Cited by 288 · see citing works
An Orthogonal Array Optimization of Lipid-like Nanoparticles for mRNA Delivery in Vivo
Li, B., Luo, X., Deng, B., Wang, J., McComb, D. W., Shi, Y., Gaensler, K. M. L., Tan, X., Dunn, A. L., Kerlin, B. A., et al. (2015) · Nano Letters · doi:10.1021/acs.nanolett.5b03528 · Cited by 261 · see citing works
Li, M., Zhao, M., Fu, Y., Li, Y., Gong, T., Zhang, Z., & Sun, X. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.02.043 · Cited by 201 · see citing works
Bogers, W. M., Oostermeijer, H., Mooij, P., Koopman, G., Verschoor, E. J., Davis, D., Ulmer, J. B., Brito, L. A., Cu, Y., Banerjee, K., et al. (2015) · Journal of Infectious Diseases · doi:10.1093/infdis/jiu522 · Cited by 181 · see citing works
Effective mRNA pulmonary delivery by dry powder formulation of PEGylated synthetic KL4 peptide
Qiu, Y., Man, R. C. H., Liao, Q., Kung, K. L. K., Chow, M. Y. T., & Lam, J. K. W. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.10.026 · Cited by 178 · see citing works
Biomaterials for mRNA delivery
Islam, M. A., Reesor, E. K. G., Xu, Y., Zope, H. R., Zetter, B. R., & Shi, J. (2015) · Biomaterials Science · doi:10.1039/c5bm00198f · Cited by 176 · see citing works
Induction of HIV-1 gag specific immune responses by cationic micelles mediated delivery of gag mRNA
Zhao, M., Li, M., Zhang, Z., Gong, T., & Sun, X. (2016) · Drug Delivery · doi:10.3109/10717544.2015.1038856 · Cited by 132 · see citing works
Evading innate immunity in nonviral mRNA delivery: don't shoot the messenger.
Devoldere, J., Dewitte, H., De Smedt, S. C., & Remaut, K. (2016) · Drug Discovery Today · doi:10.1016/j.drudis.2015.07.009 · Cited by 112 · see citing works
Youn, H., & Chung, J.-K. (2015) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2015.1057563 · Cited by 114 · see citing works
Treatment of neurological disorders by introducing mRNA in vivo using polyplex nanomicelles
Baba, M., Itaka, K., Kondo, K., Yamasoba, T., & Kataoka, K. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.01.017 · Cited by 109 · see citing works
The ReNAissanCe of mRNA-based cancer therapy
Van Lint, S., Renmans, D., Broos, K., Dewitte, H., Lentacker, I., Heirman, C., Breckpot, K., & Thielemans, K. (2015) · Expert Review of Vaccines · doi:10.1586/14760584.2015.957685 · Cited by 95 · see citing works
Schrom, E., Huber, M., Aneja, M., Dohmen, C., Emrich, D., Geiger, J., Hasenpusch, G., Herrmann-Janson, A., Kretzschmann, V., Mykhailyk, O., et al. (2017) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2017.04.006 · Cited by 69 · see citing works
Therapeutic Prospects of mRNA-Based Gene Therapy for Glioblastoma
Tang, X., Zhang, S., Fu, R., Zhang, L., Huang, K., Peng, H., Dai, L., & Chen, Q. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.01208 · Cited by 69 · see citing works
Stability analysis of chemically modified mRNA using micropattern-based single-cell arrays
Ferizi, M., Leonhardt, C., Meggle, C., Aneja, M. K., Rudolph, C., Plank, C., & Rädler, J. O. (2015) · Lab on a Chip · doi:10.1039/c5lc00749f · Cited by 41 · see citing works
mRNA vaccination as a safe approach for specific protection from type I allergy
Weiss, R., Scheiblhofer, S., Roesler, E., Weinberger, E., & Thalhamer, J. (2012) · Expert Review of Vaccines · doi:10.1586/erv.11.168 · Cited by 42 · see citing works
- Authors
- Tavernier, G., Andries, O., Demeester, J., Sanders, N. N., De Smedt, S. C., & Rejman, J.
- Affiliations
- Ghent University (BE)
- ORCID
- Sanders, Niek N.
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 150
- Issue
- 3
- Pages
- 238-247
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W2053359824
- Cited by
- 232
- References
- 147
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 15 · 2023: 14 · 2022: 17 · 2021: 15 · 2020: 14 · 2019: 14 · 2018: 16 · 2017: 15 · 2016: 18 · 2015: 30 · 2014: 11 · 2013: 14 · 2012: 14
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- mRNA stability, mRNA transfection, CpG motifs, mRNA modification, electroporation, lipoplexes, polyplexes, mRNA vaccines
- MeSH terms
- Animals, Humans, Immunotherapy, Neoplasms, RNA, Messenger, Transfection
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