Department of Biotechnology, Jaypee Institute of Information Technology, A-10, Sector-62, NOIDA-201307, Uttar Pradesh, India.
Recent Pat Anticancer Drug Discov. 2012 Jan;7(1):102-17. doi: 10.2174/157489212798357958.
Telomerase, a specialised RNA-directed DNA polymerase extends and stabilises the telomeres at the ends of the eukaryotic chromosomes. The progressive loss of telomeres results in limited number of cell divisions and has been linked to the mechanism of human cellular ageing. Tumour cells marked by indefinite proliferation have stable telomere length maintained by telomerase. The differential expression of the telomerase enzyme in normal and cancer cells have led to the evolution of tumour specific anti-telomerase approaches which inhibit the telomerase enzyme activity so as to destabilise and shorten the telomeres leading to senescence in cancer cells. In the current review, we have selected nine tumour specific anti-telomerase approaches based on their mechanism of action or the target components of the human telomerase enzyme: Antisense-oligonucleotides, hammerhead ribozymes, dominant negative hTERT, reverse-transcriptase inhibitors, immunotherapy, G-quadruplex stabilisers, gene therapy, small molecule inhibitors and RNA interference. Recent research developments for each of the anti-telomerase approaches with the detailed analysis of specific granted patents from the perspective of different claims and downstream applications have been provided. A comprehensive list of patents for the different anti-telomerase approaches which includes information regarding the authors and institutional ownership along with the year of issue of the patent has also been provided.
端粒酶是一种特殊的 RNA 指导的 DNA 聚合酶,可延长和稳定真核染色体末端的端粒。端粒的逐渐丢失导致细胞分裂次数有限,与人类细胞衰老的机制有关。标记为无限增殖的肿瘤细胞通过端粒酶维持稳定的端粒长度。端粒酶在正常细胞和癌细胞中的差异表达导致了肿瘤特异性抗端粒酶方法的发展,这些方法抑制端粒酶的活性,从而使端粒不稳定和缩短,导致癌细胞衰老。在本综述中,我们根据其作用机制或人端粒酶的靶成分选择了九种肿瘤特异性抗端粒酶方法:反义寡核苷酸、锤头核酶、显性负 hTERT、逆转录酶抑制剂、免疫疗法、G-四链体稳定剂、基因疗法、小分子抑制剂和 RNA 干扰。提供了每种抗端粒酶方法的最新研究进展,并从不同权利要求和下游应用的角度详细分析了特定授予的专利。还提供了不同抗端粒酶方法的专利的综合清单,其中包括有关作者和机构所有权以及专利发布年份的信息。