Direct Gene Transfer into Mouse Muscle in Vivo

Wolff, Jon A.; Malone, Robert W.; Williams, Phillip; Chong, Wang; Acsadi, Gyula; Jani, Agnes; Felgner, Philip L.

doi:10.1126/science.1690918

Cited by 4,173RNA Interference and Gene DeliveryVirus-based gene therapy researchIntramuscular injections and effects

Direct Gene Transfer into Mouse Muscle in Vivo

Wolff, Jon A., Malone, Robert W., Williams, Phillip, Chong, Wang, Acsadi, Gyula, Jani, Agnes, Felgner, Philip L.·1990·Science

DOI 10.1126/science.1690918

Open this paper in CoChat — free account

Abstract

RNA and DNA expression vectors containing genes for chloramphenicol acetyltransferase, luciferase, and β-galactosidase were separately injected into mouse skeletal muscle in vivo. Protein expression was readily detected in all cases, and no special delivery system was required for these effects. The extent of expression from both the RNA and DNA constructs was comparable to that obtained from fibroblasts transfected in vitro under optimal conditions. In situ cytochemical staining for β-galactosidase activity was localized to muscle cells following injection of the β-galactosidase DNA vector. After injection of the DNA luciferase expression vector, luciferase activity was present in the muscle for at least 2 months.

Integrity signals

Registry

Crossref · 10.1126/science.1690918

Cites

28 of 28 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Direct injection of mRNA or pDNA into the skeletal muscle of a mouse resulted in expression of the encoded protein.
“In 1990, Wolff et al. (5) demonstrated that direct injection (”
From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [5]
Exogenous mRNA can direct protein expression in vivo.
“Following initial studies in the early 1990s demonstrating that exogenous mRNA can direct protein expression in vivo, mRNA has emerged as a promising drug platform technology in recent years (Wolff et al, 1990; Jirikowski et al, 1992).”
From mRNA mediates passive vaccination against infectious agents, toxins, and tumors (2017) · cites this paper as Wolff et al, 1990
The improvement of RNA kinetics by these modifications may also be of interest for other cellular settings, such as T cells, B cells, and muscle cells.
“In principle, the improvement of RNA kinetics by these modifications is not restricted to DCs but is similar in K562 cells and may also be of interest for other cellular settings, such as T cells, 43 B cells, 44 and muscle cells, 45 which are attractive host cells for the expression of IVT RNA-encoded proteins.”
From Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells (2006) · cites this paper as [45]

Recombinant Genomes Which Express Chloramphenicol Acetyltransferase in Mammalian Cells
Gorman, C., Moffat, L. F., & Howard, B. H. (1982) · Molecular and Cellular Biology · doi:10.1128/mcb.2.9.1044 · Cited by 7,673 · see citing works
Selective extraction of polyoma DNA from infected mouse cell cultures
Hirt, B. (1967) · Journal of Molecular Biology · doi:10.1016/0022-2836(67)90307-5 · Cited by 5,294 · see citing works
Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure.
Felgner, P. L., Gadek, T. R., Holm, M., Roman, R., Chan, H. W., Wenz, M., Northrop, J. P., RINGOLD, G. M., & Danielsen, M. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.21.7413 · Cited by 4,954 · see citing works
Self-citation
Firefly Luciferase Gene: Structure and Expression in Mammalian Cells
de Wet, J. R., Wood, K. V., DeLuca, M., Helinski, D. R., & Subramani, S. E. (1987) · Molecular and Cellular Biology · doi:10.1128/mcb.7.2.725 · Cited by 3,088 · see citing works
Functional messenger RNAs are produced by SP6 <i>in vitro</i> transcription of cloned cDNAs
Krieg, P. A., & Melton, D. A. (1984) · Nucleic Acids Research · doi:10.1093/nar/12.18.7057 · Cited by 1,533 · see citing works
The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection.
Gorman, C. M., Merlino, G. T., Willingham, M. C., Pastan, I. H., & Howard, B. H. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.22.6777 · Cited by 1,298 · see citing works
Cationic liposome-mediated transfection
Felgner, P. L., & RINGOLD, G. M. (1989) · Nature · doi:10.1038/337387a0 · Cited by 989 · see citing works
Self-citation
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
Self-citation
Lineage analysis in the vertebrate nervous system by retrovirus-mediated gene transfer.
Price, J., Turner, D., & Cepko, C. L. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.1.156 · Cited by 878 · see citing works
Receptor-mediated gene delivery and expression in vivo.
Wu, G. Y., & Wu, C. H. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)68081-0 · Cited by 636 · see citing works
Sperm cells as vectors for introducing foreign DNA into eggs: Genetic transformation of mice
Lavitrano, M., Camaioni, A., Fazio, V. M., Dolci, S., Farace, M. G., & Spadafora, C. (1989) · Cell · doi:10.1016/0092-8674(89)90787-3 · Cited by 537 · see citing works
Progress Toward Human Gene Therapy
Friedmann, T. (1989) · Science · doi:10.1126/science.2660259 · Cited by 481 · see citing works
Increased Expression of DNA Cointroduced with Nuclear Protein in Adult Rat Liver
Kaneda, Y., Iwai, K., & Uchida, T. (1989) · Science · doi:10.1126/science.2911748 · Cited by 455 · see citing works
Bacterial beta-galactosidase as a marker of Rous sarcoma virus gene expression and replication.
Norton, P. A., & Coffin, J. M. (1985) · Molecular and Cellular Biology · doi:10.1128/mcb.5.2.281 · Cited by 206 · see citing works
In vivo expression of rat insulin after intravenous administration of the liposome-entrapped gene for rat insulin I.
Nicolau, C. S., Pape, A. L., Soriano, P. M., Fargette, F., & Mf, J. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.4.1068 · Cited by 169 · see citing works
Direct transfection of viral and plasmid DNA into the liver or spleen of mice.
Dubensky, T. W., Campbell, B. A., & Villarreal, L. P. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.23.7529 · Cited by 106 · see citing works
Grafting genetically modified cells into the rat brain: characteristics of E. coli β-galactosidase as a reporter gene
Shimohama, S., Rosenberg, M. B., Fagan, A. M., Wolff, J. A., Short, M. P., Breakefield, X. O., Friedmann, T., & Gage, F. H. (1989) · Molecular Brain Research · doi:10.1016/0169-328x(89)90061-2 · Cited by 105 · see citing works
Self-citation
Direct introduction of genes into rats and expression of the genes.
Benvenisty, N., & Reshef, L. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.24.9551 · Cited by 101 · see citing works
Retroviral vectors for introduction of genes into mammalian cells.
Eglitis, M. A., & Anderson, W. F. (1990) · PubMed · Cited by 98 · see citing works
Liposome‐mediated gene transfer
Mannino, R. J., & Gould-Fogerite, S. (2015) · The Dictionary of Genomics, Transcriptomics and Proteomics · doi:10.1002/9783527678679.dg06877 · Cited by 96 · see citing works
Transfer of a Protein Encoded by a Single Nucleus to Nearby Nuclei in Multinucleated Myotubes
Ralston, E., & Hall, Z. W. (1989) · Science · doi:10.1126/science.2543074 · Cited by 88 · see citing works
Evidence for two mechanisms by which tumor necrosis factor kills cells
Reid, T. R., Torti, F. M., & RINGOLD, G. M. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)83783-8 · Cited by 77 · see citing works
The cloned genome of ground squirrel hepatitis virus is infectious in the animal.
Seeger, C., Ganem, D., & VARMUS, H. E. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.18.5849 · Cited by 67 · see citing works
Persistent human immunodeficiency virus type 1 infection of monoblastoid cells leads to accumulation of self-integrated viral DNA and to production of defective virions
Pauza, C. D., & Galindo, J. (1989) · Journal of Virology · doi:10.1128/jvi.63.9.3700-3707.1989 · Cited by 58 · see citing works
Homologous Plasmid Recombination Is Elevated in Immortally Transformed Cells
Finn, G. K., Kurz, B. W., Cheng, R. Z., & Reis, R. J. S. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.9.4009 · Cited by 50 · see citing works
Penetration of horseradish peroxidase into the terminal cisternae of frog skeletal muscle fibers and blockade of caffeine contracture by Ca++ depletion
Rubio, R., & Sperelakis, N. (1972) · Cell and Tissue Research · doi:10.1007/bf00335454 · Cited by 34 · see citing works
Somatic gene therapy for human disease: Background and prospects. Part I
Ledley, F. D. (1987) · The Journal of Pediatrics · doi:10.1016/s0022-3476(87)80278-0 · Cited by 25 · see citing works
Penetration of horseradish peroxidase into the terminal cisternae of frog skeletal muscle fibers and blockade of caffeine contracture by Ca++ depletion
Rubio, R., & Sperelakis, N. (1972) · Cell and Tissue Research · doi:10.1007/bf00981941 · Cited by 18 · see citing works

Flagged first, then by citations

Sorted by citations

mRNA vaccines — a new era in vaccinology
Pardi, N., Hogan, M. J., Porter, F. W., & Weissman, D. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.243 · Cited by 4,667 · see citing works
Lipid nanoparticles for mRNA delivery
Hou, X., Zaks, T., Langer, R., & Dong, Y. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00358-0 · Cited by 4,076 · see citing works
Effect of Surface Properties on Nanoparticle–Cell Interactions
Verma, A., & Stellacci, F. (2009) · Small · doi:10.1002/smll.200901158 · Cited by 2,621 · see citing works
mRNA-based therapeutics--developing a new class of drugs
Sahin, U., Karikó, K., & Türeci, Ö. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4278 · Cited by 2,474 · see citing works
Nonviral vectors for gene delivery
Mintzer, M. A., & Simanek, E. E. (2009) · Chemical Reviews · doi:10.1021/cr800409e · Cited by 2,366 · see citing works
Heterologous Protection Against Influenza by Injection of DNA Encoding a Viral Protein
Ulmer, J. B., Donnelly, J., Parker, S. E., Rhodes, G. H., Felgner, P. L., Dwarki, V., Gromkowski, S. H., Deck, R. R., DeWitt, C. M., Friedman, A., et al. (1993) · Science · doi:10.1126/science.8456302 · Cited by 2,318 · see citing works
Self-citation
Incorporation of Pseudouridine Into mRNA Yields Superior Nonimmunogenic Vector With Increased Translational Capacity and Biological Stability
Karikó, K., Muramatsu, H., Welsh, F. A., Ludwig, J., Kato, H., Akira, S., & Weissman, D. (2008) · Molecular Therapy · doi:10.1038/mt.2008.200 · Cited by 1,930 · see citing works
Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA
Liu, F., Song, Y. K., & Liu, D. (1999) · Gene Therapy · doi:10.1038/sj.gt.3300947 · Cited by 1,728 · see citing works
Synthetic DNA delivery systems
Luo, D., & Saltzman, W. M. (2000) · Nature Biotechnology · doi:10.1038/71889 · Cited by 1,625 · see citing works
Pluronic® block copolymers as novel polymer therapeutics for drug and gene delivery
Kabanov, A. V., Batrakova, E. V., & Alakhov, V. Y. (2002) · Journal of Controlled Release · doi:10.1016/s0168-3659(02)00009-3 · Cited by 1,474 · see citing works
The current landscape of nucleic acid therapeutics
Kulkarni, J. A., Witzigmann, D., Thomson, S. B., Chen, S., Leavitt, B. R., Cullis, P. R., & van der Meel, R. (2021) · Nature Nanotechnology · doi:10.1038/s41565-021-00898-0 · Cited by 1,371 · see citing works
DNA Vaccines: Immunology, Application, and Optimization
Gurunathan, S., Klinman, D. M., & Seder, R. A. (2000) · Annual Review of Immunology · doi:10.1146/annurev.immunol.18.1.927 · Cited by 1,198 · see citing works
Overcoming cellular barriers for RNA therapeutics
Dowdy, S. F. (2017) · Nature Biotechnology · doi:10.1038/nbt.3802 · Cited by 1,139 · see citing works
DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations.
Fynan, E. F., Webster, R. G., FULLER, D. H., Haynes, J. R., Santoro, J. C., & Robinson, H. L. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.24.11478 · Cited by 1,116 · see citing works
Constitutive Expression of phVEGF 165 After Intramuscular Gene Transfer Promotes Collateral Vessel Development in Patients With Critical Limb Ischemia
Baumgärtner, I., Pieczek, A., Manor, O., Blair, R. H., Kearney, M., Walsh, K., & Isner, J. M. (1998) · Circulation · doi:10.1161/01.cir.97.12.1114 · Cited by 1,098 · see citing works
Efficient transfer of genetic material into mammalian cells using Starburst polyamidoamine dendrimers.
Kukowska‐Latallo, J. F., Bielinska, A. U., Johnson, J., Spindler, R., Tomalia, D. A., & Baker, J. R. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.10.4897 · Cited by 1,006 · see citing works
DNA VACCINES
Donnelly, J., Ulmer, J. B., Shiver, J. W., & Liu, M. A. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.617 · Cited by 985 · see citing works
Dendrimers in gene delivery
Dufès, C., Uchegbu, I. F., & Schätzlein, A. G. (2005) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2005.09.017 · Cited by 984 · see citing works
Gene transfer into muscle by electroporation in vivo
Aihara, H., & Miyazaki, J. (1998) · Nature Biotechnology · doi:10.1038/nbt0998-867 · Cited by 945 · see citing works
High Levels of Foreign Gene Expression in Hepatocytes after Tail Vein Injections of Naked Plasmid DNA
Zhang, G., Budker, V. G., & Wolff, J. A. (1999) · Human Gene Therapy · doi:10.1089/10430349950017734 · Cited by 944 · see citing works
Self-citation
mRNA vaccine for cancer immunotherapy
Miao, L., Zhang, Y., & Huang, L. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01335-5 · Cited by 947 · see citing works
“The first report of the successful expression of in vitro transcription (IVT) mRNA in mouse skeletal muscle cells through direct injection into animals was published in 1990, underlining the feasibility of mRNA vaccine development [9].”
Background
The mdx mouse diaphragm reproduces the degenerative changes of Duchenne muscular dystrophy
Stedman, H. H., Sweeney, H. L., Shrager, J. B., Maguire, H., Panettieri, R., Petrof, B., Narusawa, M., Leferovich, J. M., Sladky, J. T., & Kelly, A. M. (1991) · Nature · doi:10.1038/352536a0 · Cited by 925 · see citing works
High-efficiency gene transfer into skeletal muscle mediated by electric pulses.
Mir, L. M., Bureau, M., Gehl, J., Rangara, R., Rouy, D., Caillaud, J., Delaère, P., Branellec, D., Schwartz, B., & Scherman, D. (1999) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.96.8.4262 · Cited by 972 · see citing works
Efficient long-term gene transfer into muscle tissue of immunocompetent mice by adeno-associated virus vector
Xiao, X., Li, J., & Samulski, R. J. (1996) · Journal of Virology · doi:10.1128/jvi.70.11.8098-8108.1996 · Cited by 913 · see citing works
Human gene therapy comes of age
Miller, A. D. (1992) · Nature · doi:10.1038/357455a0 · Cited by 908 · see citing works
CpG DNA as a vaccine adjuvant
Bode, C., Zhao, G., Steinhagen, F., Kinjo, T., & Klinman, D. M. (2011) · Expert Review of Vaccines · doi:10.1586/erv.10.174 · Cited by 895 · see citing works
Control of Viremia and Prevention of Clinical AIDS in Rhesus Monkeys by Cytokine-Augmented DNA Vaccination
Barouch, D. H., Santra, S., Schmitz, J. E., Kuroda, M. J., Fu, T., Wagner, W., Bilska, M., Craiu, A., Zheng, X. X., Krivulka, G. R., et al. (2000) · Science · doi:10.1126/science.290.5491.486 · Cited by 881 · see citing works
Advances in Biomaterials for Drug Delivery
Fenton, O. S., Olafson, K. N., Pillai, P. S., Mitchell, M. J., & Langer, R. (2018) · Advanced Materials · doi:10.1002/adma.201705328 · Cited by 869 · see citing works
Induction of Antigen-Specific Cytotoxic T Lymphocytes in Humans by a Malaria DNA Vaccine
Wang, R., Doolan, D. L., Le, T. P., Hedstrom, R. C., Coonan, K., Charoenvit, Y., Jones, T. R., Hobart, P. M., Margalith, M., Ng, J., et al. (1998) · Science · doi:10.1126/science.282.5388.476 · Cited by 833 · see citing works
Biologically erodable microspheres as potential oral drug delivery systems
Mathiowitz, E., Jacob, J. S., Jong, Y. S., Carino, G. P., Chickering, D. E., Chaturvedi, P., Santos, C. A., Vijayaraghavan, K., Montgomery, S., Bassett, M., et al. (1997) · Nature · doi:10.1038/386410a0 · Cited by 823 · see citing works
The clinical progress of mRNA vaccines and immunotherapies
Barbier, A. J., Jiang, A. Y., Zhang, P., Wooster, R., & Anderson, D. G. (2022) · Nature Biotechnology · doi:10.1038/s41587-022-01294-2 · Cited by 823 · see citing works
“A typical lipid nanoparticle (LNP) formulation is composed of (1) an ionizable or cationic lipid to interact with the polyanionic RNA, (2) a helper phospholipid (for example, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)) that resemble the lipids in the cell membra…”
Background
DNA–based immunization by in vivo transfection of dendritic cells
Condon, C., Watkins, S. C., Celluzzi, C. M., Thompson, K., & Falo, L. D. (1996) · Nature Medicine · doi:10.1038/nm1096-1122 · Cited by 820 · see citing works
Comparing COVID-19 vaccines for their characteristics, efficacy and effectiveness against SARS-CoV-2 and variants of concern: a narrative review
Fiolet, T., Kherabi, Y., MacDonald, C.-J., Ghosn, J., & Peiffer-Smadja, N. (2022) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2021.10.005 · Cited by 911 · see citing works
“In 1990, the direct injection of mRNA in mouse muscle cells proved the feasibility of mRNA vaccines [12].”
Tools for translation: non-viral materials for therapeutic mRNA delivery
Hajj, K. A., & Whitehead, K. A. (2017) · Nature Reviews Materials · doi:10.1038/natrevmats.2017.56 · Cited by 799 · see citing works
mRNA-based therapeutics: powerful and versatile tools to combat diseases
Qin, S., Tang, X., Chen, Y., Chen, K., Fan, N., Xiao, W., Zheng, Q., Li, G., Teng, Y., Wu, M., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01007-w · Cited by 801 · see citing works
“Phase 1, mRNA discovery, in vitro synthesis and nucleic acid delivery system construction (1961–1990), including discovery mRNA(523) and using protamine for RNA delivery,(524) in vitro translation of isolated mRNA,(525) mRNA cap was discovered,(526) Liposome-entrapped mRNA delivery,(527) Cap analog commercialized, T7…”
Background
SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far
Rabi, F. A., Zoubi, M. S. A., KASASBEH, G., Salameh, D. M., & Al‐Nasser, A. D. (2020) · Pathogens · doi:10.3390/pathogens9030231 · Cited by 773 · see citing works
“Of interest is the use of a relatively new vaccine technology, RNA vaccines that have the ability to elicit potent immune responses against infectious diseases and certain cancers [77,78].”
Background
Efficient Gene Transfer into the Embryonic Mouse Brain Using in Vivo Electroporation
Saito, T., & Nakatsuji, N. (2001) · Developmental Biology · doi:10.1006/dbio.2001.0439 · Cited by 770 · see citing works
Cancer vaccines as promising immuno-therapeutics: platforms and current progress
Liu, J., Fu, M., Wang, M., Wan, D., Wei, Y., & Wei, X. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01247-x · Cited by 725 · see citing works
Systemic Gene Expression After Intravenous DNA Delivery into Adult Mice
Zhu, N. W., Liggitt, D., Liu, Y., & Debs, R. J. (1993) · Science · doi:10.1126/science.7687073 · Cited by 720 · see citing works
Nanodelivery of nucleic acids
Mendes, B. B., Conniot, J., Avital, A., Yao, D., Jiang, X., Zhou, X., Sharf-Pauker, N., Xiao, Y., Adir, O., Liang, H., et al. (2022) · Nature Reviews Methods Primers · doi:10.1038/s43586-022-00104-y · Cited by 719 · see citing works
Nonviral Gene Delivery: Principle, Limitations, and Recent Progress
Al-Dosari, M. S., & Gao, X. (2009) · The AAPS Journal · doi:10.1208/s12248-009-9143-y · Cited by 706 · see citing works
N1-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice
Andries, O., Mc Cafferty, S., De Smedt, S. C., Weiss, R., Sanders, N. N., & Kitada, T. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.08.051 · Cited by 701 · 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 mRNA Vaccines for Infectious Diseases
Zhang, C., Maruggi, G., Shan, H., & Li, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00594 · Cited by 680 · 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
“Although it has been known since 1990 that nucleic acids can be used to modulate protein production in vivo [9], therapeutic RNA delivery has been limited by a number of factors.”
Background
Recombinant adeno-associated virus for muscle directed gene therapy
Fisher, K. J., Jooss, K., Alston, J., Yang, Y., Haecker, S. E., High, K., Pathak, R., Raper, S. E., & Wilson, J. M. (1997) · Nature Medicine · doi:10.1038/nm0397-306 · Cited by 654 · see citing works
Gene inoculation generates immune responses against human immunodeficiency virus type 1.
Wang, B., Ugen, K. E., Srikantan, V., Agadjanyan, M. G., Dang, K., Refaeli, Y., Sato, A. I., Boyer, J., Williams, W. V., & Weiner, D. B. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.9.4156 · Cited by 655 · see citing works
Design and gene delivery activity of modified polyethylenimines
Kircheis, R., Wightman, L., & Wagner, E. (2001) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(01)00202-2 · Cited by 651 · see citing works
Preclinical and clinical demonstration of immunogenicity by mRNA vaccines against H10N8 and H7N9 influenza viruses
Bahl, K., Senn, J. J., Yuzhakov, O., Bulychev, A., Brito, L. A., Hassett, K. J., Laska, M. E., Smith, M., Almarsson, Ö., Thompson, J., et al. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.03.035 · Cited by 642 · see citing works
“Although first identified in the early 1990s, mRNA vaccines were not advanced into the clinic until recently due to concerns around stability and production.(42,43) The mRNA vaccines are produced by a well-controlled, enzymatic, and well-characterized scalable process that is agnostic to the antigen being produced.”
Background
First Human Trial of a DNA-Based Vaccine for Treatment of Human Immunodeficiency Virus Type 1 Infection: Safety and Host Response
MacGregor, R. R., Boyer, J., Ugen, K. E., Lacy, K. E., Gluckman, S. J., Bagarazzi, M. L., Chattergoon, M. A., Baine, Y., Higgins, T. J., Ciccarelli, R. B., et al. (1998) · The Journal of Infectious Diseases · doi:10.1086/515613 · Cited by 640 · see citing works
RNA-based therapeutics: an overview and prospectus
Zhu, Y., Zhu, L., Wang, X., & Jin, H. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05075-2 · Cited by 658 · see citing works
“mRNAs and mRNA vaccine The concept of mRNA-encoded drugs was discovered in the 1990s when direct injection of IVT mRNA into the mouse skeletal muscle showed encoded protein expression [56].”
Background
Current status of DNA vaccines in veterinary medicine
Krishnan, B. (2000) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(00)00073-9 · Cited by 628 · see citing works
Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells
Holtkamp, S., Kreiter, S., Selmi, A., Simon, P., Koslowski, M., Huber, C., Türeci, O., & Sahin, U. (2006) · Blood · doi:10.1182/blood-2006-04-015024 · Cited by 625 · see citing works
Developing mRNA-vaccine technologies
Schlake, T., Thess, A., Fotin-Mleczek, M., & Kallen, K.-J. (2012) · RNA Biology · doi:10.4161/rna.22269 · Cited by 622 · see citing works
Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein
Kessler, P., Podsakoff, G. M., Chen, X., McQuiston, S. A., Colosi, P., Matelis, L. A., Kurtzman, G. J., & Byrne, B. J. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.14082 · Cited by 614 · see citing works
Nonviral gene therapy: promises and challenges
Li, S., & Huang, L. (2000) · Gene Therapy · doi:10.1038/sj.gt.3301110 · Cited by 610 · see citing works
Poultry coccidiosis: recent advancements in control measures and vaccine development
Dalloul, R. A., & Lillehoj, H. S. (2006) · Expert Review of Vaccines · doi:10.1586/14760584.5.1.143 · Cited by 614 · 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
Therapeutic Cancer Vaccines
Guo, C., Manjili, M. H., Subjeck, J. R., Sarkar, D., Fisher, P. B., & Wang, X. (2013) · Advances in cancer research · doi:10.1016/b978-0-12-407190-2.00007-1 · Cited by 598 · see citing works
Advances in COVID-19 mRNA vaccine development
Fang, E., Liu, X., Li, M., Zhang, Z., Song, L., Zhu, B., Wu, X., Liu, J., Zhao, D., & Li, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00950-y · Cited by 601 · see citing works
“the way for mRNA therapeutic research.(76) After immunizing mice with liposome-encapsulated mRNA encoding the influenza-virus nucleoprotein (NP), the production of anti-influenza cytotoxic T lymphocytes (CTLs) was induced in the host, thus marking a milestone in the development of the first mRNA vaccine.”
Background
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
“The development of mRNA‐based drugs dates back to 1990 with the successful expression of a number of different proteins upon injecting mRNA encoding these proteins directly into the muscles of mice [24].”
Background
Inorganic Nanoparticles as Carriers of Nucleic Acids into Cells
Sokolova, V., & Epple, M. (2007) · Angewandte Chemie International Edition · doi:10.1002/anie.200703039 · Cited by 581 · see citing works
Widespread long-term gene transfer to mouse skeletal muscles and heart.
Stratford-Perricaudet, L. D., Makeh, I., Perricaudet, M., & Briand, P. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115902 · Cited by 579 · see citing works
Nonviral Vectors in the New Millennium: Delivery Barriers in Gene Transfer
Nishikawa, M., & Huang, L. (2001) · Human Gene Therapy · doi:10.1089/104303401750195836 · Cited by 573 · see citing works
Predominant Role for Directly Transfected Dendritic Cells in Antigen Presentation to CD8+ T Cells after Gene Gun Immunization
Porgador, A., Irvine, K. R., Iwasaki, A., Barber, B. H., Restifo, N. P., & Germain, R. N. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.6.1075 · Cited by 560 · see citing works
Composition design and medical application of liposomes
Li, M., Du, C., Guo, N., Teng, Y., Meng, X., Sun, H., Li, S., Yu, P., & Galons, H. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.01.007 · Cited by 561 · see citing works
The tangled history of mRNA vaccines
Dolgin, E. (2021) · Nature · doi:10.1038/d41586-021-02483-w · Cited by 556 · see citing works
The Limitless Future of RNA Therapeutics
Damase, T. R., Sukhovershin, R. A., Boada, C., Taraballi, F., Pettigrew, R. I., & Cooke, J. P. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.628137 · Cited by 549 · see citing works
mRNA vaccines manufacturing: challenges and bottlenecks
Rosa, S. S., Prazeres, D. M. F., Azevedo, A. M., & Marques, M. P. C. (2021) · Vaccine · doi:10.1016/j.vaccine.2021.03.038 · Cited by 545 · see citing works
“[16] showed that proteins can be produced from in vitro transcribed mRNA in live tissues, mRNA vaccines have been demonstrating efficacy in a number of applications [58].”
Background
Intradermal gene immunization: the possible role of DNA uptake in the induction of cellular immunity to viruses.
Raz, E., Carson, D. A., Parker, S. E., Parr, T. B., Abai, A. M., Aichinger, G., Gromkowski, S. H., Singh, M., Lew, D., & Yankauckas, M. A. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.20.9519 · Cited by 543 · see citing works
Activation of Cutaneous Dendritic Cells by CpG-Containing Oligodeoxynucleotides: A Role for Dendritic Cells in the Augmentation of Th1 Responses by Immunostimulatory DNA
Jakob, T., Walker, P., Krieg, A. Μ., Udey, M. C., & Vogel, J. C. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.6.3042 · Cited by 535 · see citing works
Myosin isoforms in mammalian skeletal muscle
Schiaffino, S., & Reggiani, C. (1994) · Journal of Applied Physiology · doi:10.1152/jappl.1994.77.2.493 · Cited by 538 · see citing works
Chitosan-DNA nanoparticles as non-viral vectors in gene therapy: strategies to improve transfection efficacy
Mansouri, S., Lavigne, P., Corsi, K. A., Benderdour, M., Beaumont, É., & Fernandes, J. (2003) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/s0939-6411(03)00155-3 · Cited by 533 · see citing works
New Vaccine Technologies to Combat Outbreak Situations
Rauch, S., Jasny, E., Schmidt, K. E., & Petsch, B. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01963 · Cited by 579 · see citing works
“DNA vaccines in potential pandemic settings Since the first experiments in the 1990 (91), DNA vaccines have been employed for vaccine development up to clinical trials against a large variety of human pathogens such as HIV, influenza virus, malaria, hepatitis B virus, respiratory syncytial and herpes simplex virus.”
Background
mRNA as a Transformative Technology for Vaccine Development to Control Infectious Diseases
Maruggi, G., Zhang, C., Li, J., Ulmer, J. B., & Yu, D. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.01.020 · Cited by 507 · see citing works
“The seminal work from Wolff et al.(17) in 1990 provided the first successful example of in vitro-transcribed mRNA-expressing reporter proteins in the muscle after injection, which was followed by the studies of Martinon et al.”
Method
The 60-year evolution of lipid nanoparticles for nucleic acid delivery
Cullis, P. R., & Felgner, P. L. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-00977-6 · Cited by 517 · see citing works
“This unexpected finding established Vical as a leader in the field of naked DNA gene therapy and vaccines 32,37–39 .”
Self-citation
Preferential induction of a Th1 immune response and inhibition of specific IgE antibody formation by plasmid DNA immunization.
Raz, E., Tighe, H., Sato, Y., Corr, M., Dudler, J., Roman, M., Swain, S. L., Spiegelberg, H. L., & Carson, D. A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.10.5141 · Cited by 515 · see citing works
Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals
Thess, A., Grund, S., Mui, B. L., Hope, M. J., Baumhof, P., Fotin-Mleczek, M., & Schlake, T. (2015) · Molecular Therapy · doi:10.1038/mt.2015.103 · Cited by 513 · see citing works
Somatic integration and long-term transgene expression in normal and haemophilic mice using a DNA transposon system
Yant, S. R., Meuse, L. A., Chiu, W. S., Ivics, Z., Izsvák, Z., & Kay, M. A. (2000) · Nature Genetics · doi:10.1038/75568 · Cited by 509 · see citing works
Algorithm for optimized mRNA design improves stability and immunogenicity
Zhang, H., Zhang, L., Lin, A., Xu, C., Li, Z., Liu, K., Liu, B., Ma, X., Zhao, F., Jiang, H., et al. (2023) · Nature · doi:10.1038/s41586-023-06127-z · Cited by 498 · see citing works
mRNA-based cancer therapeutics
Liu, C., Shi, Q., Huang, X., Koo, S., Kong, N., & Tao, W. (2023) · Nature Reviews Cancer · doi:10.1038/s41568-023-00586-2 · Cited by 500 · see citing works
Cationic microparticles: A potent delivery system for DNA vaccines
Singh, M., Briones, M., Ott, G. S., & O’Hagan, D. T. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.2.811 · Cited by 489 · see citing works
Human dystrophin expression in mdx mice after intramuscular injection of DNA constructs
Acsádi, G., Dickson, G., Love, D. R., Jáni, Á., Walsh, F. S., Gurusinghe, A. D., Wolff, J. A., & Davies, K. E. (1991) · Nature · doi:10.1038/352815a0 · Cited by 485 · see citing works
Self-citation
Gene therapy by skeletal muscle expression of decorin prevents fibrotic disease in rat kidney
Isaka, Y., Brees, D. K., Ikegaya, K., Kaneda, Y., Imai, E., Noble, N. A., & Border, W. A. (1996) · Nature Medicine · doi:10.1038/nm0496-418 · Cited by 481 · see citing works
DNA Complexes with Polycations for the Delivery of Genetic Material into Cells
Kabanov, A. V., & Kabanov, V. A. (1995) · Bioconjugate Chemistry · doi:10.1021/bc00031a002 · Cited by 481 · see citing works
Manipulation of the immune response to a plasmid-encoded viral antigen by coinoculation with plasmids expressing cytokines
Xiang, Z., & Ertl, H. C. J. (1995) · Immunity · doi:10.1016/s1074-7613(95)80001-8 · Cited by 477 · see citing works
Gene vaccination with naked plasmid DNA: mechanism of CTL priming.
Corr, M., Lee, D. J., Carson, D. A., & Tighe, H. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.184.4.1555 · Cited by 476 · 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
Delivery of bioactive molecules into the cell: the Trojan horse approach
Dietz, G. P. H., & Bähr, M. (2004) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2004.03.005 · Cited by 469 · see citing works
DNA vaccines: an historical perspective and view to the future
Liu, M. A. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00980.x · Cited by 469 · see citing works
Modifications in an Emergency: The Role of N1-Methylpseudouridine in COVID-19 Vaccines
Nance, K. D., & Meier, J. L. (2021) · ACS Central Science · doi:10.1021/acscentsci.1c00197 · Cited by 466 · see citing works
A Comprehensive Review of mRNA Vaccines
Gote, V., Bolla, P. K., Kommineni, N., Butreddy, A., Nukala, P. K., Palakurthi, S. S., & Khan, W. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032700 · Cited by 457 · see citing works
“Although the early efforts in the 1990s to produce an effective in vitro transcribed (IVT) mRNA vaccine in animal models’ epitope presentation were effective [6,7], mRNA vaccines and therapeutics were not developed, as they were not validated until the late 1900s.”
Background
Microspheres for controlled release drug delivery
Varde, N. K., & Pack, D. W. (2004) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.4.1.35 · Cited by 451 · see citing works
DNA Vaccines: Progress and Challenges
Donnelly, J., Wahrén, B., & Liu, M. A. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.2.633 · Cited by 449 · see citing works
Detailed Analysis of Structures and Formulations of Cationic Lipids for Efficient Gene Transfer to the Lung
Lee, E. R., Marshall, J., Siegel, C., Jiang, C., Yew, N. S., Nichols, M., Nietupski, J. B., Ziegler, R. J., Lane, M. B., Wang, K. X., et al. (1996) · Human Gene Therapy · doi:10.1089/hum.1996.7.14-1701 · Cited by 443 · see citing works
Key issues in non-viral gene delivery
Pouton, C. W., & Seymour, L. W. (1998) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(98)00048-9 · Cited by 440 · see citing works
Gene Therapy by Intramuscular Injection of Plasmid DNA: Studies on Firefly Luciferase Gene Expression in Mice
Manthorpe, M., Cornefert-Jensen, F., Hartikka, J., Felgner, J. H., Rundell, A., Margalith, M., & Dwarki, V. (1993) · Human Gene Therapy · doi:10.1089/hum.1993.4.4-419 · Cited by 432 · see citing works
Nonviral gene delivery: What we know and what is next
Gao, X., Kim, K., & Liu, D. (2007) · The AAPS Journal · doi:10.1208/aapsj0901009 · Cited by 431 · see citing works
A Comparison of Plasmid DNA and mRNA as Vaccine Technologies
Liu, M. A. (2019) · Vaccines · doi:10.3390/vaccines7020037 · Cited by 428 · see citing works
“It was found that cross-priming appeared to be a key mechanism for generating CTLs following DNA vaccine immunization, as directly demonstrated by experiments with chimeric mice using bone-marrow derived dendritic cells [27], and because muscle cells were the only cells observed to translate the protein encoded by dir…”
BackgroundResult
Protection against a lethal influenza virus challenge by immunization with a haemagglutinin-expressing plasmid DNA
Robinson, H. L., Hunt, L., & Webster, R. G. (1993) · Vaccine · doi:10.1016/0264-410x(93)90385-b · Cited by 428 · see citing works

Conditions affecting direct gene transfer into rodent muscle in vivo.
Wolff, J. A., Williams, P., Acsádi, G., Jiao, S., Jani, A., & Chong, W. (1991) · PubMed · Cited by 260 · see citing works
Self-citation
Direct DNA injection into mouse tongue muscle for analysis of promoter function in vivo
Prigozy, T. I., Dalrymple, K. R., Kedes, L., & Shuler, C. F. (1993) · Somatic Cell and Molecular Genetics · doi:10.1007/bf01233527 · Cited by 20 · see citing works
High expression of naked plasmid DNA in muscles of young rodents
Dankó, I. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.9.1435 · Cited by 92 · see citing works
Spatial–temporal patterns of gene expression in mouse skeletal muscle after injection of lacZ plasmid DNA
Doh, S. G., Vahlsing, H. L., Hartikka, J., Liang, X., & Manthorpe, M. (1997) · Gene Therapy · doi:10.1038/sj.gt.3300460 · Cited by 76 · see citing works
DNA Injection into Single Cells of Intact Mice
Utvik, J. K., Njå, A., & Gundersen, K. (1999) · Human Gene Therapy · doi:10.1089/10430349950019075 · Cited by 49 · see citing works

Authors: Wolff, J. A., Malone, R. W., Williams, P., Chong, W., Acsadi, G., Jani, A., & Felgner, P. L.
Affiliations: University of Wisconsin–Madison (US)
Vical (United States) (US)
Departments of Pediatrics and Genetics, Waisman Center, University of Wisconsin, Madison, WI 53706.
ORCID: Malone, Robert W.
Felgner, Philip L.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1990-03-23
Volume: 247
Issue: 4949
Pages: 1465-1468
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1690918
OpenAlex: W2014495927
Cited by: 4,173
References: 27
Citations by year: 2026: 96 · 2025: 151 · 2024: 186 · 2023: 201 · 2022: 188 · 2021: 187 · 2020: 81 · 2019: 74 · 2018: 62 · 2017: 66 · 2016: 56 · 2015: 77 · 2014: 68 · 2013: 93 · 2012: 90
FWCI: 26.43
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5k11hd000669-02)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 03352, HD00669-05, P30HD003352)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Health Sciences › Medicine › Emergency Medicine › Intramuscular injections and effects
Keywords: in vivo gene delivery, skeletal muscle, intramuscular injection, DNA vectors, chloramphenicol acetyltransferase, luciferase, beta-galactosidase, transgene expression, cytochemical staining, transfection
MeSH terms: Animals, Avian Sarcoma Viruses, Coleoptera, beta-Galactosidase, DNA, Escherichia coli, Genetic Vectors, Histocytochemistry, Luciferases, Muscles, RNA, Transfection, Chloramphenicol O-Acetyltransferase, Gene Expression, 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

Direct Gene Transfer into Mouse Muscle in Vivo

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks