Cristiano R J
Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Anticancer Res. 1998 Sep-Oct;18(5A):3241-5.
Our research has focused on developing improved delivery vectors for treating cancer by gene therapy using the tumor suppressor p53 gene.
Recombinant viral and non-viral vectors were used to deliver the p53 gene into non-small cell lung cancer (NSCLC) cells either in culture or as a subcutaneous tumor. Transduction of tumor cells was measured by beta-gal expression while tumor cell proliferation was used to measure the effect of p53.
High level transduction was obtained in vitro and in vivo with a recombinant adenoviral vector, resulting in tumor cell growth inhibition in both models. A targeted, non-viral gene delivery vector based on the use of an EGF/DNA polyplex also resulted in efficient (as high as 66% transduction) and specific gene delivery in vitro when replication defective adenovirus was used as an endosome release agent.
These vectors now provide improved methods to deliver therapeutic genes for cancer treatment by gene therapy.
我们的研究聚焦于开发改良的递送载体,通过使用肿瘤抑制基因p53进行基因治疗来治疗癌症。
使用重组病毒载体和非病毒载体,将p53基因导入培养的非小细胞肺癌(NSCLC)细胞或皮下肿瘤中。通过β-半乳糖苷酶表达来检测肿瘤细胞的转导情况,同时利用肿瘤细胞增殖来衡量p53的作用效果。
使用重组腺病毒载体在体外和体内均获得了高水平的转导,在两种模型中均导致肿瘤细胞生长受到抑制。当使用复制缺陷型腺病毒作为内体释放剂时,基于表皮生长因子(EGF)/DNA多聚体的靶向非病毒基因递送载体在体外也能实现高效(高达66%的转导率)且特异性的基因递送。
这些载体为通过基因治疗递送治疗性基因用于癌症治疗提供了改良方法。