Abstract
Striated muscle has recently been shown to be an excellent target tissue for gene transfer in vivo. Both skeletal and cardiac muscle are post-mitotic highly stable structures; consequently gene transfer into these tissues produces long-lasting gene expression. A number of gene transfer systems work effectively with skeletal muscle, including retroviral gene vectors (Dunckley et al., 1993) and adenoviral vectors (Ragot et al., 1993) but the simplest method is the direct injection of naked plasmid DNA into the muscle. Gene uptake and expression following in vivo transfection with plasmid DNA is substantially higher in striated muscle compared with any other tissue (Acsadi et al., 1991a). This methodology, first reported by Wolff and coworkers (1990), has attracted considerable interest as a means of in vivo gene therapy for a wide range of diseases. Skeletal muscle can serve as a platform for systemic gene expression; for example the production of Factor VIII for the treatment of hemophilia A, as well as being the target for treatment, as in the case of Duchenne muscular dystrophy. Plasmid DNA can also be used as a means of delivering genetic vaccination, an approach that potentially can give rise to effective long-lasting humoral and cell-mediated immunity following a single treatment (see Chapter 18).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Acsadi, G., Jiao, S., Jani, A. et al. (1991a) Direct gene transfer and expression into rat heart in vivo. New Biologist, 3, 71–81.
Acsadi, G., Dickson, G., Love, D.R. et al. (1991b) Human dystrophin expression in mdx mice after intra-muscular injection of DNA constructs. Nature, 352, 815–18.
Bassel-Duby, R., Grohe, C.M., Jesson, M.E. et al. (1993) Sequence elements required for transcriptional activity of the human myoglobin promoter in intact myocardium. Circ. Res., 73, 360–6.
Buttrick, P.M., Kass, A., Kitsis, R.N., Kaplan, M.L. and Leinwand, L.A. (1992) Behavior of genes directly injected into the rat heart in vivo. Circ. Res., 70, 193–8.
Danko, I., Fritz, J.D., Jiao, S., Hogan, K., Latendresse, J.S. and Wolff, J.A. (1994) Pharmacological enhancement of in vivo foreign gene expression in muscle. Gene Therapy, 1, 114–21.
Davis, H.L. and Jasmin, B.J. (1993) Direct gene transfer into mouse diaphragm. FEBS Lett., 333, 146–50.
Davis, H.L., Whalen, R.G. and Demeneix, B.A. (1993a) Direct gene transfer into skeletal muscle in vivo: factors affecting efficiency of transfer and stability of expression. Human Gene Ther., 4, 151–9.
Davis, H.L., Demeneix, B.A., Quantin, B., Coulombe, J. and Whalen, R.G. (1993b) Plasmid DNA is superior to viral vectors for direct gene transfer into adult mouse skeletal muscle. Human Gene Ther., 4, 733–40.
Dowty, M.E. and Wolff, J.A. (1994) Possible mechanisms of DNA uptake in skeletal muscle, in Gene Therapeutics: Methods and Applications of Direct Gene Transfer, (ed. J.A. Wolff), Birkhauser, Boston, pp. 82–98.
Dunckley, M.G., Wells, D.J., Walsh, F.S. and G. Dickson (1993) Direct retroviral-mediated transfer of a dystrophin minigene into mdx mouse muscle in vivo. Hum. Mol. Genet., 2, 717–23.
Dunckley, M., Piper, T., Wells, K.E., Wells, D.J. and Dickson, G. (1994) Independent localisation of dystrophin N- and C-terminal regions to the sarcolemma of mdx mouse myofibres in vivo. J. Cell Sci., 107, 1469–75.
Edwards, J.G., Bahl, J.J., Flink, I., Milavetz, J., Goldman, S. and Morkin, E. (1992) A repressor region in the human beta-myosin heavy chain gene that has a partial position dependency. Biochem. Biophys. Res. Commun., 189, 504–10.
Fazio, V.M., Fazio, S., Rinaldi, M. et al. (1994) Accumulation of human Apolipoprotein-E in rat plasma after in vivo intramuscular injection of naked DNA. Biochem. Biophys. Res. Commun., 200, 298–305.
Gal, D., Weir, L., Leclerc, G., Pickering, J.G., Hogan, J. and Isner, J.M. (1993) Direct myocardial transfection in two animal models: evaluation of parameters affecting gene expression and percutaneous gene delivery. Lab. Invest., 68, 18–25.
Hansen, E., Fernandes, K., Goldspink, G., Butterworth, P., Umeda, P. and Chang, K-C. (1991) Strong expression of foreign genes following direct injection into fish muscle. FEBS Lett., 290, 73–6.
Jiao, S.S., Williams, P., Berg, R.K. et al. (1992) Direct gene transfer into nonhuman primate myofibres in vivo. Human Gene Ther., 3, 21–33.
Kitsis, R.N., Buttrick, P., McNally, E., Kaplan, M. and Leinwand, L.A. (1991) Hormonal modulation of a gene injected into rat heart in vivo. Proc. Natl Acad. Sci. USA, 88, 4138–42.
LeBlanc, J.M., Kitsis, R.N., Buttrick, P.M. and Leinwand, L.A. (1992) Molecular genetic manipulation of cardiac myosin, in Neuromuscular Development and Disease, (eds A.M. Kelly and H.M. Blau), Raven Press, New York, pp. 223–37.
Leiden, J.M. and Barr, E. (1994) In vivo gene transfer into the heart, in Gene Therapeutics: Methods and Applications of Direct Gene Transfer, (ed. ), Birkhauser, Boston, pp. 363–81.
Leinwand, L.A. and Leiden, J.M. (1991) Gene transfer into cardiac myocytes in vivo. Trends Cardiovasc. Med., 1, 271–6.
Lin, H., Parmacek, M.S., Morle, G., Boiling, S. and Leiden, J.M. (1990) Expression of recombinant genes in myocardium in vivo after direct injection of DNA. Circulation, 82, 2217–21.
Manthorpe, M., Cornefert-Jensen, F., Hartikka, J. et al. (1993) Gene therapy by intramuscular injection of plasmid DNA: studies on firefly luciferase gene expression in mice. Human Gene Ther., 4, 419–31.
Parmacek, M.S., Vora, A.J., Shen, T., Barr, E., Jung, F. and Leiden, J.M. (1992) Identification and characterization of a cardiac-specific transcriptional regulatory element in the slow/cardiac troponin C gene. Mol. Cell. Biol., 12, 1967–76.
Ragot, T., Vincent, N., Chafey, P. et al. (1993) Efficient adenovirus-mediated transfer of a human minidystrophin gene to skeletal muscle of mdx mice. Nature, 361, 647–50.
Raz, E., Watanabe, A., Baird, S.M. et al. (1993) Systemic immunological effects of cytokine genes injected into skeletal muscle. Proc. Natl Acad. Sci. USA, 90, 4523–7.
Ulmer, J.B., Donnelly, J.J. and Liu, M.A. (1993) Polynucleotide vaccines. Curr. Opin. Invest. Drugs, 2(9), 983–9.
Vincent, C.K., Gualberto, A., Patel, C.V. and Walsh, K. (1993) Different regulatory sequences control creatine kinase-M gene expression in directly injected skeletal and cardiac muscle. Mol. Cell. Biol., 13, 1264–72.
Vitadello, M., Schiaffino, M.V., Picard, A., Scarpa, M. and Schiaffino, S. (1994) Gene transfer in regenerating muscle. Human Gene Ther., 5, 11–18.
von-Harsdorf, R., Schott, R.J., Shen, Y.T., Vatner, S.F., Mahdavi, V. and Nadal-Ginard, B. (1993) Gene injection into canine myocardium as a useful model for studying gene expression in the heart of large mammals. Circ. Res., 72, 688–95.
Wells, D.J. (1993) Improved gene transfer by direct plasmid injection associated with regeneration in mouse skeletal muscle. FEBS Lett., 332, 179–82.
Wells, D.J. and Goldspink, G. (1992) Age and sex influence expression of plasmid DNA directly injected into mouse skeletal muscle. FEBS Lett., 306, 203–5.
Wolff, J.A., Malone, R.W., Williams, P. et al. (1990) Direct gene transfer into mouse muscle in vivo. Science, 247, 1465–8.
Wolff, J.A., Williams, P., Acsadi, G., Jiao, S., Jani, A. and Wang, C. (1991) Conditions affecting direct gene transfer into rodent muscle in vivo. Biotechniques, 11, 474–85.
Wolff, J.A., Ludtke, J.J., Acsadi, G., Williams, P. and Jani, A. (1992a) Long-term persistence of plasmid DNA and foreign gene expression in mouse muscle. Hum. Mol. Genet., 1, 363–9.
Wolff, J.A., Dowry, M.E., Jiao, S. et al. (1992b) Expression of naked plasmids by cultured myotubes and entry of plasmids into T tubules and caveolae of mammalian skeletal muscle. J. Cell Sci., 103, 1249–59.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1995 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Wells, D.J. (1995). Intramuscular injection of plasmid DNA. In: Dickson, G. (eds) Molecular and Cell Biology of Human Gene Therapeutics. Molecular and Cell Biology of Human Diseases Series, vol 20. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-0547-7_5
Download citation
DOI: https://doi.org/10.1007/978-94-011-0547-7_5
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-010-4242-0
Online ISBN: 978-94-011-0547-7
eBook Packages: Springer Book Archive