Inhibition of telomerase in tumor cells by ribozyme targeting telomerase RNA component.

Telomerase plays an important role in cell proliferation and carcinogenesis and is believed to be a good target for anti-cancer drugs. Elimination of template function of telomerase RNA may repress the telomerase activity. A hammer-headed ribozyme (telomerase ribozyme, teloRZ) directed against the RNA component of human telomerase (hTR) was designed and synthesized.

[Preliminary analysis on human telomerase reverse transcriptase gene expression in acute leukemia].

Objective: To explore the relationship between gene expression of human telomerase reverse transcriptase (hTERT) and its clinical characteristics in leukemia.

Methods: The protocol of RT-PCR was used to detect the hTERTmRNA expressing levels in peripheral blood samples from leukemic patients under primary treatment(n=42), in complete remission(n=21), with recurrent leukemia (n=4); and from normal subjects (n=5), respectively.

Results: The positive percentage of hTERTmRNA expression was 73.

[Attenuation of telomerase activity by hammerhead ribozyme targeting the 5'-end of hTERT mRNA].

Objective: To assess the telomerase activity inhibitory effect of ham merhead ribozyme targeting the 5'-end of human telomerase reverse transcriptase mRNA (hTERT-5'RZ), to compare it with the effect of another ribozyme teloRZ, and the combine the applications of the two ribozymes.

Methods: hTERT-5'RZ gene was synthesized and cloned into pcDNA3.1(+); the ribozyme was produced by in vitro transcription.

Structural analysis of human CCR2b and primate CCR2b by molecular modeling and molecular dynamics simulation.

CCR2b, a chemokine receptor for MCP-1, -2, -3, -4, plays an important role in a variety of diseases involving infection, inflammation, and/or injury, as well as being a coreceptor for HIV-1 infection. Two models of human CCR2b (hCCR2b) were generated by homology modeling and 1 ns restrained molecular dynamics (MD) simulation. In one only C113-C190 forms a disulfide bond (SS model); in another the potential C32-C277 disulfide bond was formed (2SS model).