Prevention and Treatment of Cervical Cancer

描述（由申请人提供）：Arbor Vita提出验证致癌E6变体与特定细胞蛋白家族的相互作用，作为人乳头瘤病毒（HPV）感染和宫颈癌治疗干预的靶点。HPV的致癌变异体与宫颈癌相关，频率为99.7%。已发表和未发表的数据将HPV致癌性与含有特定结合基序或配体的HPV E6癌蛋白变体相关联。具体来说，Arbor Vita提议1）鉴定致癌E6变体靶向的人类蛋白质家族成员2）确认宫颈细胞系中靶蛋白的表达3）确认体内发生的靶相互作用4）证明干扰致癌E6配体/细胞蛋白质相互作用减少细胞分析中的致癌转化，5）开发致癌E6配体/蛋白质相互作用的小分子抑制剂的体外筛选。为了实现这些目标，Arbor Vita将利用其专有的体外试验，可用于筛选相互作用，确定亲和力，并筛选小分子破坏靶向相互作用的能力。包括肽生产/纯化、克隆、蛋白质生产/纯化和小分子合成。将使用基于细胞的试验（包括软琼脂/转化试验和qPCR分析）确定体内效应。

DESCRIPTION (provided by applicant): Arbor Vita proposes to validate the interactions of oncogenic E6 variants with a specific cellular protein family as a target for therapeutic intervention in Human papilloma virus (HPV) infection and cervical cancer. Oncogenic variants of HPVs have been correlated with cervical cancer at a frequency of 99.7%. Published and unpublished data has correlated HPV oncogenicity with variants of HPV E6 oncoprotein that contain a particular binding motif or ligand. Specifically, Arbor Vita proposes to 1) identify the human protein family members targeted by oncogenic E6 variants 2) confirm expression of target proteins in cervical cell lines 3) confirm target interaction occurs in vivo 4) demonstrate that interfering with the oncogenic E6 ligand/cellular protein interaction reduces oncogenic transformation in cellular assays and, 5) develop an in vitro screen for small molecule inhibitors of the oncogenic E6 ligand/protein interaction. To accomplish these aims Arbor Vita will utilize it's proprietary in vitro assay that can be used to screen interactions, determine affinity, and screen small molecules for the ability to disrupt the targeted interaction. Included are peptide production/purification, cloning, protein production/purification, and small molecule synthesis. Cell based assays including soft agar/transformation assays and qPCR analysis will be used to determine in vivo effects.