Possible Mechanisms of DNA Uptake in Skeletal Muscle

  • Martin E. Dowty
  • Jon A. Wolff


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.


Neisseria Gonorrhoeae Luciferase Expression Mouse Muscle Direct Gene Transfer Polyglutamic Acid 
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© Birkhäuser Boston 1994

Authors and Affiliations

  • Martin E. Dowty
  • Jon A. Wolff

There are no affiliations available

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