Spatiotemporal Depletion of Connexins Using Antisense Oligonucleotides

Abstract

Antisense oligodeoxynucleotides have considerable potential as agents for the manipulation of specific gene expression (2–3). They function by entering the cell and binding to the messenger RNA (mRNA), thereby blocking protein translation (See Note 1). The short half-life of oligonucleotides can be overcome, sustained delivery can be achieved, and specific tissue targeting can be obtained using a Pluronic gel delivery system. It is therefore possible to gain an understanding of the roles of connexins, which are expressed in dynamic and spatially controlled patterns, through transient reduction in the expression of specific connexin proteins. This leads to dramatic but precisely defined aberrations in embryonic development, for example (3). The major advantage of the approach is the ability to achieve spatiotemporal regulation of connexin gene expression while reducing some of the problems associated with gene knockout approaches (see Tables 1 and 2 ).

Table 1 Advantages of an Antisense Oligodeoxynucleotide Knockdown Approach Compared with the Gene Knockout Approach for Regulating Gene Expression

Table 2 Some Disadvantages of the Antisense Oligodeoxynucleotide Knockdown Approach Compared with the Gene Knockout Approach for Regulating Gene Expression