The Combinatorial Design of Protein Molecular Switches

描述（由申请人提供）：作为开关的蛋白质作为选择性蛋白质疗法具有很大的前景。PI先前的研究已经证明，通过在两个基因之间创造大量不同的融合，并使这些基因融合在实验室中进化，可以设计蛋白质开关。这种定向进化策略将用于开发和改进蛋白质开关，以有效地选择性地激活癌细胞中的前药。这些开关将通过内源性表达和全身递送来评估其在体内消除肿瘤异种影像的能力。这些开关与适当的前药相结合，有可能成为治疗癌症的靶向治疗方法。

DESCRIPTION (provided by applicant): Proteins that behave as switches hold great promise as selective protein therapeutics. Previous studies by the PI have demonstrated that protein switches can be engineered by creating a large number of different fusions between two genes and subjecting these gene fusions to evolution in the lab. Such directed evolution strategies will be used to develop and improve protein switches to effectively activate prodrugs selectively in cancer cells. These switches will be evaluated for their ability to eliminate tumor xenographs in vivo using endogenous expression and via systemic delivery. These switches in combination with the appropriate prodrug have potential as a targeted therapeutic for the treatment of cancer.