Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
PURPOSE: To test ribozymes targeting mouse telomerase RNA (mTER) for suppression of the progression of B16-F10 murine melanoma metastases in vivo. EXPERIMENTAL DESIGN: Hammerhead ribozymes were designed to target mTER. The ribozyme sequences were cloned into a plasmid expression vector containing EBV genomic elements that substantially prolong expression of genes delivered in vivo. The activity of various antitelomerase ribozymes or control constructs was examined after i.v. injection of cationic liposome:DNA complexes containing control or ribozyme constructs.
We have analyzed the de novo telomere synthesis catalyzed by the enzyme telomere terminal transferase (telomerase) from Tetrahymena. Oligonucleotides representing the G-rich strand of telomeric sequences from five different organisms specifically primed the addition of TTGGGG repeats in vitro, suggesting that primer recognition may involve a DNA structure unique to these oligonucleotides. The sequence at the 3' end of the oligonucleotide primer specified the first nucleotide added in the reaction.
Cold Spring Harbor Symposia on Quantitative Biology
Telomeres are maintained by the ribonucleoprotein (RNP) enzyme telomerase, which replenishes telomeres through its unique mechanism of internal RNA-templated addition of telomeric DNA. Telomerase is active in most human cancers, typically because its core protein subunit, TERT, is up-regulated. Although the major known function of telomerase in cancer is to replenish telomeric DNA and maintain cell immortality, the regulation of the RNA component of telomerase is not well understood.