乳腺癌是女性中发病率最高的恶性肿瘤。本课题申请人及国外相关研究均显示溶瘤性单纯疱疹病毒G47△对乳腺癌有较好的疗效，我们还初步证实了G47△能有效的杀灭乳腺癌干细胞。但因该病毒的γ34.5基因被剔除而降低了繁殖能力，使其对部分乳腺癌细胞与干细胞无明显杀伤作用。我们希望降低病毒副作用的同时，仍然保留病毒对肿瘤有效的杀伤力。因此，对其基因进一步改造显得非常必要。 最近研究发现病毒的致病因子为γ34.5基因编码蛋白的第68至87位氨基酸，敲除该段序列后，病毒的毒性显著下降，但复制能力未受明显影响。本课题拟将敲除该段序列的γ34.5基因回插入G47△中，增加其复制能力，研发出消除了毒性而复制能力仍强劲的新型第四代病毒载体G68△，进一步通过体外实验及动物体内实验证实其对多种乳腺癌及干细胞的治疗作用，预计其疗效将明显优于现今肿瘤基因治疗的第三代病毒载体G47△，给乳腺癌治疗带来一种确实有效的新方法。

The incidence breast cancer is highest one in women. Our research and relative reports from foreign countries showed the oncolytic herpes simplex virus, G47△ is sensitive for breast cancer.And it is also able to kill the breast cancer stem cells effectively. However, it's replication become limited because of knock out of r34.5 gene, and it can not be as a good killer for some breast cancer cells and breast cancer stem cells. We hope the virus can keep the same sensitivity for cancer cells as diminishing the side effects. Therefore, it is needed to be reconstucted for it's genes. Recent study showed that viral nosogenesis depends on the amino acid 68-87 which is coded by the gene r34.5. The virulence will be declined if this gene is knocked out.But it can keep the same ability of replication. In this proposal we will insert G47△ with the gene r34.5 without the special sequence,and then increase the replication of virus, which is called the forth generation, G68△. We will validate the treatment for multiple breast cancer cell lines and breast cancer stem cells. It is expected more effecitive than the third generation of virus,G47△. It will be a new affirmatory method for the treatment of breast cancer.