Skip to main content
SpringerLink
Log in

Possible Mechanisms of DNA Uptake in Skeletal Muscle

  • Chapter
Gene Therapeutics

Abstract

Somatic gene therapy promises to be a revolutionary advance in the medical treatment of both acquired and genetic disease states. The major obstacle for the full realization of gene therapy is currently the ability to transfer the appropriate gene into enough target cells which will result in sufficient levels of protein expression to control the biological disorder. A number of methods to transfer genes into cells are currently being explored and include viral (Miller, 1990), physical (Capecchi, 1980; Chu et al., 1987; Wu and Wu, 1988; Wolff et al., 1990; Mirzayans et al., 1992), and chemical (Benvenity and Reshef, 1986; Felgner et al., 1987; Felgner and Ringold, 1989; Yang et al., 1990) techniques. With each of these methods, the gene needs to traverse the cell membrane and, subsequently, enter the nucleus where it can be expressed. The processes involved in the transfer of DNA across biological membranes are, at this time, mostly speculative and require more research to fully define the processes involved in polynucleotide transport. This chapter will discuss what is known about the uptake of naked foreign DNA by muscle cells after intramuscular injection or implantation as well as speculate as to the possible mechanism of cellular uptake based on current data. An understanding of the mechanism by which a polynucleotide traverses the external lamina and sarcolemma of a myofiber, and subsequently enters the nucleus, should allow for the refinement of methods to deliver foreign DNA to muscle cells. It would also increase our knowledge of basic muscle physiology to learn whether there is an intrinsic property of muscle cells which allows them to take up DNA or whether it is a vagary of the delivery method.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Acsadi G, Jiao S, Jani A, Duke D, Williams P, Wang C, Wolff JA (1991a): Direct gene transfer and expression into rat heart in vivo. The New Biologist 3: 71–81

    PubMed  CAS  Google Scholar 

  • Acsadi G, Dickson G, Love DR, Jani A, Walsh FS, Gurusinghe A, Wolff JA, Davies KE (1991b): Human dystrophin expression in mdx mice after intramuscular injection of DNA constructs. Nature 352: 815–818

    Article  PubMed  CAS  Google Scholar 

  • Anderson R (1981): Cell surface membrane structure and the function of endothelial cells. In Structure and Function of the Circulation, vol. 3 (ed. CJ Schwartz, N Werthessen, and S Wolf ), pp. 239–86. New York: Plenum Press

    Google Scholar 

  • Anderson RGW, Kamen BA, Rothberg KG, Lacey SW (1992): Potocytosis: sequestration and transport of small molecules by caveolae. Science 255: 410–411

    Article  PubMed  CAS  Google Scholar 

  • Bennet RM, Gabor GT, Merritt MM (1985): DNA binding to human leukocytes; evidence for a receptor-mediated association, internalization, and degradation of DNA. J Clin Invest 76: 2182–2190

    Article  Google Scholar 

  • Bennet RM, Hefeneider SH, Bakke A, Merritt M, Smith CA, Mourich D, Heinrich MC (1988): The production and characterization of murine monoclonal antibodies to a DNA receptor on human leukocytes. J Immunology 140: 2937–2942

    CAS  Google Scholar 

  • Benvenisty N, Reshef L (1986): Direct introduction of genes into rats and expression of the genes. Proc Natl Acad Sci USA 83: 9551–9555

    Article  PubMed  CAS  Google Scholar 

  • Biswas GD, Lacks SA, Sparling PF (1989): Transformation-deficient mutants of piliated Neisseria gonorrhea Q. J Bacteriology 171: 657–664

    CAS  Google Scholar 

  • Brinster RL, Chen HY, Trumbauer ME, Yagle MK, Palmiter RD (1985): Factors affecting the efficiency of introducing foreign DNA into mice by microinjecting eggs. Proc Natl Acad Sci USA 82: 4438–4442

    Article  PubMed  CAS  Google Scholar 

  • Buttrick PM, Kass A, Kitsis RN, Kaplan ML, Leinwand LA (1992): Behavior of genes directly injected into the rat heart in vivo. Circulation Research 70: 193–198

    PubMed  CAS  Google Scholar 

  • Capecchi MR (1980): High efficiency transformation by direct microinjection of DNA into cultured mammalian cells. Cell 22: 479–488

    Article  PubMed  CAS  Google Scholar 

  • Chin DJ, Green GA, Zon G, Szoka Jr FC, Straubinger RM (1990): Rapid nuclear accumulation of injected oligodeoxyribonecleotides. The New Biologist 2: 1091–1100

    PubMed  CAS  Google Scholar 

  • Chu G, Hayakawa H, Berg P (1987): Electroporation for the efficient transfection of mammalian cells with DNA. Nucleic Acids Res 15: 1311–1326

    Article  PubMed  CAS  Google Scholar 

  • Concino MF, Goodgal SH (1981): Haemophilus influenzae polypeptides involved in deoxyribonucleic acid uptake detected by cellular surface protein iodination. J Bacteriology 148: 220–231

    CAS  Google Scholar 

  • Danner DB, Smith HO, Narang SA (1982): Construct of DNA recognition sites active in Haemophilus transformation. Proc Natl Acad Sci USA 79: 2393–2397

    Article  PubMed  CAS  Google Scholar 

  • de Wet JR, Wood KV, DeLuca M, Helinski DR, Subramani S (1987): Firefly luciferase gene; structure and expression in mammalian cells. Mol Cell Biol 7: 725

    PubMed  Google Scholar 

  • Dorward DW, Garon CF, Judd RC (1989): Export and intercellular transfer of DNA via membrane blebs of Neisseria gonorrhoeae. J Bacteriology 171: 2399–2505

    Google Scholar 

  • Edge M (1970): Development of apposed sarcoplasmic reticulum at the T system and sarcolemma and the change in orientation of triads in rat skeletal muscle. Dev Biol 23: 634–650

    Article  PubMed  CAS  Google Scholar 

  • Felgner PL, Gadek TR, Holm M, Roman R, Chan HW, Wenz M, Northrop JP, Ringold GM, Danielsen M (1987): Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc Natl Acad Sci USA 84: 7413–7417

    Article  PubMed  CAS  Google Scholar 

  • Feigner PL, Ringold GM (1989): Cationic liposome-mediated transfection. Nature 337: 387–388

    Article  Google Scholar 

  • Franzini-Armstrong C (1986) The sarcoplasmic reticulum and the transverse tubules. In: Myology. (ed. AG Engel and BQ Banker ) pp. 125–153. New York: McGraw-Hill

    Google Scholar 

  • Horwitz AF, Schotland DL (1986): The plasma membrane of the muscle fiber. In: Myology. (ed. AG Engel and BQ Banker ) pp. 177–207. New York: McGraw-Hill

    Google Scholar 

  • Huxley HE (1964): Evidence for continuity between the central elements of the triads and extracellular space in frog sartorius muscle. Nature 202: 1067–1071

    Article  PubMed  CAS  Google Scholar 

  • Janeczko RA, Carriere RM, Etlinger JD (1985): Endocytosis, proteolysis, and exocytosis of exogenous proteins by cultured myotubes. J Biol Chem 260: 7051–7058

    PubMed  CAS  Google Scholar 

  • Jiao S, Acsadi G, Jani A, Felgner P, Wolff JA (1992a): Persistence of plasmid DNA and expression in rat brain cells in vivo. Exp Neuro 115: 400–413

    Article  CAS  Google Scholar 

  • Jiao S, Williams P, Berg RK, Hodgeman BA, Liu L, Repetto G, Wolff JA (1992b): Direct gene transfer into non-human primate myofibers in vivo. Human Gene Therapy 3: 21–33

    Article  PubMed  CAS  Google Scholar 

  • Jiao S, Gurevich V, Wolff JA (1993) Long-term correction of rat model of Parkinson’s disease by gene therapy. Nature 362: 450–453

    Article  PubMed  CAS  Google Scholar 

  • Kahn ME, Maul G, Goodgal SH (1982): Possible mechanism for donor DNA binding and transport in Haemophilus. Proc Natl Acad Sci USA 79: 6370–6374

    Article  PubMed  CAS  Google Scholar 

  • Kaneda A, Iwai K, Uchida T (1989): Increased expression of DNA cointroduced with nuclear protein in adult rat liver. Science 243: 375–378

    Article  PubMed  CAS  Google Scholar 

  • Kitsis RN, Buttrick PM, McNally EM, Kaplan ML, Leinwand LA (1991) Hormonal modulation of a gene injected into rat heart in vivo. Proc Natl Acad Sci USA 88: 4138–4142

    Article  PubMed  CAS  Google Scholar 

  • Lacks S, Greenberg B (1976): Single-strand breakage on binding of DNA to cells in the genetic transformation of Diplococcus pneumoniae. J Mol Biol 101: 255–175

    Article  PubMed  CAS  Google Scholar 

  • Lin SS, Levitan IB (1991): Concanavalin A: a tool to investigate neuronal plasticity. Trends in Neuroscience 14: 273–277

    Article  CAS  Google Scholar 

  • Loke S, Stein C, Zhang X, Mori K, Nakanishi M, Subasinghe C, Cohen J (1989): Characterization of oligonucleotides transport into living cells. Proc Natl Acad Sci USA 86: 3474–3478

    Article  PubMed  CAS  Google Scholar 

  • Malone RW, Hickman MA, Lehmann K, Walzem R, Bassiri M, Powell JS (1993) Hepatic gene transfer following direct in vivo injection. J Cell Biochem 17E: 239

    Google Scholar 

  • McNeil PL (1991): Cell wounding and healing. American Scientist 79: 222–235

    Google Scholar 

  • McNeil PL, Ito S (1989): Gastrointestinal cell membrane wounding and resealing in vivo. Gastroenterology 96: 1238–1248

    PubMed  CAS  Google Scholar 

  • McNeil PL, Kahkee R (1992) Disruptions of muscle fiber plasma membranes: role in exercise-induced damage. Am J Path 140: 1097–1109

    PubMed  CAS  Google Scholar 

  • Miller AD (1990): Retrovirus packaging cells. Hum Gene Ther 1: 5–14

    Article  PubMed  CAS  Google Scholar 

  • Mirzayans R, Aubin RA, Paterson MC (1992): Differential expression and stability of foreign genes introduced into human fibroblasts by nuclear versus cytoplasmic microinjection. Mutation Res 281: 115–122

    Article  PubMed  CAS  Google Scholar 

  • Ralston E, Hall Z (1989): Transfer of protein encoded by a single nucleus to nearby nuclei in multinucleated myotubes. Science 244: 1066–1069

    Article  PubMed  CAS  Google Scholar 

  • Schiaffino S, Margreth A (1969): Coordinated development of the sarcoplasmic reticulum and T system during postnatal differentiation of rat skeletal muscle. J Cell Biol 41: 855–875

    Article  PubMed  CAS  Google Scholar 

  • Sikes ML, O’Malley Jr BW, Ledley FD (1993) In vivo gene transfer into rabbit thyroid by direct DNA injection: a novel strategy for gene therapy. J Cell Biochem 17E: 208

    Google Scholar 

  • Shoji Y, Akhtar S, Periasamy A, Herman B, Juliano RL (1991): Mechanism of cellular uptake of modified oligodeozynucleotides containing methylphosphonate linkages. Nucl Acid Res 19: 5543–5550

    Article  CAS  Google Scholar 

  • Thorburn AM, Alberts AS (1993): Efficient expression of miniprep plasmid DNA after needle microinjection into somatic cells. Bio Techniques 14: 356–358

    CAS  Google Scholar 

  • Wirtz P, Loermans H, Peer P, Reintjes A (1983): Postnatal growth and differentiation of muscle fibers in the mouse. I. a histochemical and morphometrical investigation of normal muscle. J Anat 137: 109–126

    PubMed  Google Scholar 

  • Wolff J A, Ludtke J J, Acsadi G, Williams P, Agnes J (1992a): Long-term persistence of plasmid DNA and foreign gene expression in mouse muscle. Human Molecular Genetics 1: 363–369

    Article  PubMed  CAS  Google Scholar 

  • Wolff JA, Dowty ME, Jiao S, Repetto G, Berg RK, Ludtke JJ, Williams P (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: 1249–1259

    PubMed  CAS  Google Scholar 

  • Wolff J A, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Feigner PL (1990): Direct gene transfer into mouse muscle in vivo. Science 247: 1465–1468

    Article  PubMed  CAS  Google Scholar 

  • Wolff JA, Williams P, Acsadi G, Jiao S, Jani A, Wang C (1991): Conditions affecting direct gene transfer into rodent muscle in vivo. Bio Techniques 11: 474–485

    CAS  Google Scholar 

  • Wu GY, Wu CH (1988): Receptor-mediated gene delivery and expression in vivo. J Biol Chem 263: 14621–14624

    PubMed  CAS  Google Scholar 

  • Wu-Pong S, Weiss TL, Hunt CA (1992): Antisense c-myc oligodeoxyribo-nucleotide cellular uptake. Pharm Res 9: 1010–1017

    Article  PubMed  CAS  Google Scholar 

  • Yakubov L, Deeva E, Zarytova V, Ivanova E, Ryte A, Yurchenko L, Vlassov V (1989): Mechanism of oligonucleotides uptake by cells: involvement of specific receptors. Proc Natl Acad Sci USA 86: 6454–6458

    Article  PubMed  CAS  Google Scholar 

  • Yang NS, Burkholder J, Roberts B, Martinell B, MeCabe D (1990): In vivo and in vitro gene transfer to mammalian somatic cells by particle bombardment. Proc Natl Acad Sci USA 87: 9568–9572

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Martin E. Dowty
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jon A. Wolff
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pediatrics, University of Wisconsin Medical School, Waisman Center, Room 607 1500 Highland Avenue, Madison, WI, 53705-2208, USA

    Jon A. Wolff

  2. Department of Medical Genetics, University of Wisconsin Medical School, Waisman Center, Room 607 1500 Highland Avenue, Madison, WI, 53705-2208, USA

    Jon A. Wolff

  3. Department of Neurology, University of Wisconsin Medical School, Waisman Center, Room 607 1500 Highland Avenue, Madison, WI, 53705-2208, USA

    Jon A. Wolff

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Birkhäuser Boston

About this chapter

Cite this chapter

Dowty, M.E., Wolff, J.A. (1994). Possible Mechanisms of DNA Uptake in Skeletal Muscle. In: Wolff, J.A. (eds) Gene Therapeutics. Birkhäuser Boston. https://doi.org/10.1007/978-1-4684-6822-9_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-6822-9_5

  • Publisher Name: Birkhäuser Boston

  • Print ISBN: 978-1-4684-6824-3

  • Online ISBN: 978-1-4684-6822-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation