Cellular Internalization of Oligodeoxynucleotides

  • Leonard M. Neckers


Although the addition of oligodeoxynucleotides to cell cultures has been demonstrated to effectively inhibit intracellular gene expression, such findings have been in contrast to the prevailing view that cells are impermeable to negatively charged large molecules. With this in mind, several groups have attempted to modify oligos in order to circumvent the problem of negative charge. Thus, methylphosphonates are ionically neutral, and poly-L-lysine has been linked to oligos to supply a strong positive charge. Others have made various oligonucleotide-protein conjugates to aid internalization, while the benefits of oligo encapsulation into liposomes have also been explored. During the last several years, it has become clear that even highly negatively charged oligonucleotides (i.e., phosphodiesters and phosphorothioates) are actively internalized by cells in culture. Furthermore, it has become equally apparent that backbone or pendant oligonucleotide modifications can alter olionucleotide uptake characteristics, although not always in the way intended. In this chapter, we will review the current state of knowledge concerning internalization pathways for modified and unmodified oligonucleotides and how these pathways may affect the intracellular trafficking of oligonucleotides.


Herpes Simplex Virus Type Cellular Internalization Acidic Compartment Phosphorothioate Oligos Endocytic Uptake 
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© Birkhäuser Boston 1994

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  • Leonard M. Neckers

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