2001年，笔者提出了癌症的靶向基因-病毒治疗（cancer targeting gene-viro-therapy, CTGVT）的概念，即将一个抗癌基因插入到溶瘤病毒（oncolytic virus，OV）中，从而将基因治疗与溶瘤病毒各自的优势结合起来，由于溶瘤病毒能大量复制，插入其中的基因也能大量复制，故其抗肿瘤效果大增，较单用基因治疗或OV治疗强数十至上百倍。随后又引入双基因策略（CTGVT-DG），即向OV载体插入两个抗癌基因，由于两个抗癌基因之间可能存在互补或协同效应，在一些动物癌症模型中几乎能杀灭全部移植性肿瘤。近年来又采用纳米粒子把CTGVT-DG病毒颗粒包被，或者采用溶瘤痘病毒（OncoPox）作为载体与CTGVT-DG策略相结合，后者将可构建一系列抗癌作用极好的双基因OncoPox-gene1-gene2产物。国外多数使用OV-GM-CSF策略，仅局限于GM-CSF的免疫功能，忽视了基因复制的剂量效应及其重要性，这就是中国的CTGVT-DG胜过西方的优势之处。

The author proposed the concept of cancer targeting gene-viro-therapy (CTGVT) in 2001. By inserting an anti-tumor gene into an oncolytic virus (OV), this novel approach combines the advantages of both gene therapy and OV therapy. The anti-tumor effect of CTGVT can be several dozens to hundred times higher than that of either respective cancer gene therapy or OV therapy alone, owing to the fact that OV can target to the cancer cell where both the virus and the inserted gene replicate several tens or hundreds of times faster than usual. Given compensatory or synergetic effects of genes, double gene strategy (CTGVT-DG) has been demonstrated in an animal model of xenograft tumor to be significantly more effective. In our approaches, the OncoAd vector is used. To minimize the OV injection-associated vector degradation, we choose to coat the CTGVT-DG products with nano-particles or to use the OncoPox vector. In the previous studies from the Western countries, only the immune effect of GM-CSF is considered in the OV-Gene system, while the replicative capacity of the gene is often ignored. As a result, our strategies may be able to more effectively eradicate tumors, thereby offering greater clinical potential.

国家重点基础研究发展计划（973计划）资助项目（No. 2011CB510104），国家自然科学基金面上项目资助（No. 81372453），上海市自然科学基金资助项目（No. 13ZR1446300）。