Targeting XXXX telomerase by antisense oligonucleotides and ribozymes.

@entity1 @entity2681 @entity3207 @entity5
@entity1 telomerase is a ribonucleoprotein enzyme complex that enables cells to maintain telomere length, allowing indefinite replicative capacity. The notion that telomerase is reactivated in 80-90% of @entity1 @entity5 has led to the proposal of telomerase as a promising therapeutic target for novel anticancer interventions. Due to its inherent accessibility to nucleic acids, telomerase appears an ideal target for strategies based on the use of antisense oligonucleotides and ribozymes that target its RNA template. In this review a summary of the different antisense- and ribozyme-based approaches used thus far to inhibit telomerase activity in @entity1 @entity5 cells is provided. All these strategies significantly inhibited the enzyme's catalytic activity in in vitro and in @entity5 models. However, while in some studies @entity5 cell growth arrest was observed as a consequence of telomere @entity3207 after prolonged telomerase inhibition, other studies have shown that antisense- and ribozyme-based treatments targeting telomerase induced rapid loss (i.e. within a few days) of @entity5 cell viability with concomitant apoptosis. In the latter case it is unlikely that cell death was related to telomere @entity2681 since the cells would not have undergone enough divisions to significantly shorten their telomeres. A possible explanation is that telomerase inhibitors may induce apoptosis in @entity5 cells directly by interfering with the capping function of the enzyme. Overall, the available results indicate antisense oligonucleotides and ribozymes as good tools to inhibit telomerase and suggest that abrogation of telomerase activity may affect @entity5 cell proliferation also through pathways that are not dependent on telomere @entity2681 .
