The tumour cell-specific nuclear targeting properties of chicken anaemia virus VP-3: potential for anti-tumour therapy

目前的趋势表明，到2012年，癌症将占澳大利亚所有死亡人数的40%，这意味着迫切需要新的抗癌策略。我们的建议旨在检测独特的肿瘤细胞特异性药物凋亡素(VP3-病毒蛋白3)的亚细胞靶向能力，这是一种由鸡贫血病毒基因组编码的小蛋白。使用不同的策略，我们已经确定了凋亡素分子的一部分，它可以有效地定位于肿瘤细胞的细胞核，但不是非肿瘤细胞。我们的实验计划旨在详细定义这种肿瘤细胞特异性靶向信号，并确定与正常细胞相比，凋亡素在肿瘤中的亚细胞定位差异的分子基础。这应该会为癌症和正常细胞之间的区别提供基本的新信息。此外，我们打算优化靶向信号并进行初步实验，以测试其在将抗肿瘤药物靶向肿瘤细胞核方面的有效性。我们的长期目标是利用凋亡素肿瘤细胞特异性核靶向信号作为模块化结构的一部分，有效地对抗癌症，最重要的是，对正常细胞和组织的损害最小。

Current trends indicate that cancer will cause 40% of all deaths in Australia by 2012, meaning that new anti-cancer strategies are urgently required. Our proposal intends to examine the subcellular targeting abilities of the unique tumour-cell specific agent apoptin (VP3 - viral protein 3), a small protein encoded by the genome of the chicken anaemia virus. Using various strategies, we have identified part of the apoptin molecule that confers efficient localisation in the nucleus of tumour cells, but not non-tumour cells. Our experimental program intends to define this tumour cell-specific targeting signal in detail, and determine the molecular basis of the differential subcellular localisation of apoptin in tumour compared to normal cells. This should contribute fundamental new information regarding the differences between cancer and normal cells. Additionally, we intend to optimise the targeting signal and perform initial experiments to test its efficacy in targeting anti-tumour drugs to the nucleus of tumour cells. Our long-term aim is to use the apoptin tumour cell-specific nuclear targeting signal as part of modular constructs to combat cancer efficiently, and above all, with minimal damage to normal cells and tissues.