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

描述(申请人提供)：可调节的DNA纳米结构以诱导NK介导的对肿瘤细胞的杀伤摘要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，也被用于生物医学应用，部分归因于它们在合成和选择特定结合活性方面的强健性质，类似于抗体。我们建议开发连接到可调DNA纳米结构上的多价适配子，它可以与效应细胞和肿瘤细胞特异性结合，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，从而促进肿瘤细胞的破坏。我们将重点构建连接在DNA纳米支架上的多价、多特异性适体，以指导自然杀伤(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系统地选择适体文库相结合来实现。此外，DNA纳米结构平台的可伸缩特性使其有可能整合额外的免疫调节配体，以协调和协同抗癌细胞的各种宿主免疫，包括体液免疫和细胞免疫反应。因此，这些适体DNA纳米结构可能会成为癌症治疗以及其他疾病的治疗方法的“神奇子弹”。 与公共卫生相关：我们建议开发一种新的杀瘤DNA纳米结构，其中多聚体细胞识别适配子将组装到可调节和可编程的DNA纳米支架上，以吸引免疫细胞攻击肿瘤细胞。

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.