IMMUNOSUPPRESSANT ANALOGS THROUGH TARGETED GENETICS

环孢菌素将移植科学领域带入了 医学的主流。 不幸的是，长期生存和质量 移植受者的生命仍然严重减少。 最近，天然产物FK-506和雷帕霉素已被证明在 研究表明，它比环孢菌素更安全、更有效。 此外，这些药物似乎协同作用，可能是因为 它们会干扰免疫反应的不同途径。 小说 化学合成的FK-506和雷帕霉素类似物 阐明这些药物的作用机制。 其他新的类似物 可能导致毒性更小的药物或联合治疗的新选择。 FermaLogic的科学家们，在基因操作方面拥有成熟的技能， 放线菌，建议发展基因技术作为替代 涉及用于生产新类似物的化学合成。 在第一阶段，a 基因系统将在生产微生物中发展。 在 第二阶段，基因工具将被用来操纵生物合成 通过靶向基因失活或替换途径。 类似物与 定制的结构修改可以通过 发酵 新的结构将获得专利，进行生物学测试， 并开放临床试验或进一步化学品的许可 感兴趣的合作伙伴的发展。

Cyclosporin brought the field of transplantation science into the mainstream of medicine. Unfortunately, long-term survival and quality of life for transplant recipients are still severely diminished. Recently, the natural products, FK-506 and rapamycin, have proven in studies to be safe, more potent, and more effective than cyclosporin. Furthermore, these drugs appear to act synergistically, possibly because they interfere with different pathways of the immune response. Novel chemically-synthesized analogs of FK-506 and rapamycin have helped elucidate the mechanism of action of these drugs. Other new analogs could lead to less toxic drugs or new choices for combination therapy. FermaLogic scientists, with proven skills in the genetic manipulation of Actinomycetes, propose to develop genetic technology as an alternative to chemical synthesis for producing novel analogs. In Phase One, a genetic system would be developed in the producing micro-organism. In Phase Two, the genetic tools would be used to manipulate the biosynthetic pathway by targeted gene inactivation or replacement. Analogs with tailored structural modifications could be produced inexpensively through fermentation. Novel structures would be patented, biologically tested, and open to licensing for clinical testing or further chemical development by interested partners.