Tjin Tham Sjin R M, Naspinski J, Birsner A E, Li C, Chan R, Lo K-M, Gillies S, Zurakowski D, Folkman J, Samulski J, Javaherian K
Vascular Biology Program, Department of Surgery, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
Cancer Gene Ther. 2006 Jun;13(6):619-27. doi: 10.1038/sj.cgt.7700938.
Developing continuous systemic delivery of endostatin has been a goal of many laboratories. We have employed a method of gene therapy utilizing different viral constructs. Here, we report that a new serotype of adeno-associated viruses, which incorporates canine endostatin, provides dose-dependent transgene expression in the circulation after intramuscular injection in mice. Elevated levels of endostatin remained stable in the circulation for at least 4 months. In vitro assays determined that the protein expressed was biologically active. Antitumor activities of the above construct demonstrated a U-shape curve, where the maximum activity was observed within a certain critical concentration range. These data suggest that an optimum dose range may be required to achieve therapeutic efficacy in large animal models.
开发内皮抑素的持续全身递送一直是许多实验室的目标。我们采用了一种利用不同病毒构建体的基因治疗方法。在此，我们报告一种新的腺相关病毒血清型，其整合了犬内皮抑素，在小鼠肌肉注射后可在循环系统中提供剂量依赖性的转基因表达。内皮抑素水平升高在循环系统中至少保持稳定4个月。体外试验确定所表达的蛋白质具有生物活性。上述构建体的抗肿瘤活性呈现出U形曲线，在某个临界浓度范围内观察到最大活性。这些数据表明，在大型动物模型中可能需要一个最佳剂量范围来实现治疗效果。
