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Tunable DNA-nanostructure to induce NK-mediated killing of tumor cells

可调节 DNA 纳米结构诱导 NK 介导的肿瘤细胞杀伤

基本信息

批准号：
8067094
负责人：
YUNG CHANG
金额：
$ 15.46万
依托单位：
ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-01 至 2013-04-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Tunable DNA-nanostructure to induce NK-mediated killing of tumor cells Summary Antibodies are important recognition molecules that have been widely used in cancer diagnosis and cancer therapy. Aptamers, which are nucleic acid-based recognition molecules, have also been exploited for biomedical applications, partly attributed to their robust nature in synthesis and selection for specific binding activity, similar to antibodies. We propose to develop multivalent aptamers linked onto tunable DNA-nanostructure that bind specifically to both the effector cell and tumor cells, thus are able to engage their interactions, which will trigger the activation of immune effector cells to facilitate destruction of tumor cells. We will focus on constructing multi-valent and multi-specific aptamers linked on DNA-nanoscaffolds to direct natural killer (NK) cells to attack tumor cells. This will be achieved by combining rational design of programmable DNA-nanoscaffolds with systemic selection of aptamer libraries. In addition, the scalable feature of the DNA-nanostructure platform makes it possible to incorporate additional immune modulating ligands to coordinate and synergize various lines of host immunity against cancer cells, including both humoral and cellular immune responses. Thus, these aptamer DNA-nanostructures can potentially function as "magic bullets" for cancer therapy, as well as therapeutics for other diseases. PUBLIC HEALTH RELEVANCE: We propose to develop a novel tumor-killing DNA-nanostructure, in which multimeric cell- recognition aptamers will be assembled onto tunable and programmable DNA-nanoscaffolds to engage immune cells to attack tumor cells.

描述（由申请人提供）：诱导 NK 介导的肿瘤细胞杀伤的可调谐 DNA 纳米结构概述抗体是重要的识别分子，已广泛用于癌症诊断和癌症治疗。适体是基于核酸的识别分子，也已被用于生物医学应用，部分原因在于它们在合成和选择特异性结合活性方面的稳健性，类似于抗体。我们建议开发连接到可调谐DNA纳米结构上的多价适体，这些适体特异性结合效应细胞和肿瘤细胞，从而能够参与它们的相互作用，从而触发免疫效应细胞的激活，以促进肿瘤细胞的破坏。我们将专注于构建连接在DNA纳米支架上的多价和多特异性适体，以引导自然杀伤（NK）细胞攻击肿瘤细胞。这将通过将可编程 DNA 纳米支架的合理设计与适体库的系统选择相结合来实现。此外，DNA纳米结构平台的可扩展特性使其能够整合额外的免疫调节配体，以协调和协同多种宿主免疫系统对抗癌细胞，包括体液和细胞免疫反应。因此，这些适体 DNA 纳米结构有可能成为癌症治疗以及其他疾病治疗的“灵丹妙药”。公共健康相关性：我们建议开发一种新型肿瘤杀伤DNA纳米结构，其中多聚细胞识别适体将被组装到可调谐和可编程的DNA纳米支架上，以吸引免疫细胞攻击肿瘤细胞。