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

摘要抗体是一种重要的识别分子，已广泛应用于癌症诊断和治疗中。适配体是一种基于核酸的识别分子，也被用于生物医学应用，部分原因是它们在合成和选择特定结合活性方面的强大特性，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体，这些适体可以特异性地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，从而促进肿瘤细胞的破坏。我们将重点构建连接在dna纳米支架上的多价和多特异性适配体，以指导自然杀伤细胞（NK）攻击肿瘤细胞。这将通过合理设计可编程dna纳米支架与系统选择适体库相结合来实现。此外，dna -纳米结构平台的可扩展特性使其能够结合额外的免疫调节配体来协调和协同各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纳米结构可以作为癌症治疗的“灵丹妙药”，以及其他疾病的治疗方法。

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.