Multivalent Binding of Spatially Patterned Nucleic Acid Nanostructures

DNA作为生物学中遗传信息的载体，正越来越多地被用于非生物应用。连接在一起(杂交)形成扭曲形状的遗传物质的两条链现在被设计成以不同的方式连接起来形成非生物纳米结构。通过杂交精确组装核酸使DNA纳米化学领域发生了革命性的变化，因为它允许人们使用简单的碱基配对规则来设计复杂的三维结构。在化学系大分子、超分子和纳米化学(MSN)计划的支持下，埃默里大学的Khalid Salaita教授正在开发更高的结合强度和长链DNA的特异性，通过利用形成相互加强的多个键的能力来形成纳米结构。该项目的重点是空间图案化的互补DNA短链，它们协同发挥作用，结合目标核酸。提高靶向DNA与特定靶点结合的强度和特异性对于DNA技术在传感、诊断和治疗应用中的应用至关重要。在进行这项研究的过程中，研究生和本科生接受了DNA纳米技术方面的培训。K-12学生获得暑期研究经验，研究成果被纳入科学演示和面向普通公众的视频剪辑中。这个项目的具体目标是研究一类多价态，其中正交配体-受体对以空间定义的方式排列。这种“空间有序的异多价态”目前还没有被用于DNA纳米结构的形成，它可能为大分子和超分子设计提供新的策略。Salaita教授致力于开发具有增强结合能力的新型空间图案核酸纳米颗粒的合成方法和详细表征。支持这一努力的假设是，显示在颗粒表面的寡核苷酸的空间组织可能会导致与互补核酸靶标结合的亲和力和特异性大大增强。这项工作的一个目标是开发在金纳米颗粒表面空间排列核酸的方法。图案化颗粒的结合亲和力和特异性将作为总片段数、片段密度和片段的分子灵活性的函数进行测试。另一个目标是制造图案化的脂质体颗粒。图案化几何和锚定化学的影响将通过测量这些结构的完整热力学结合常数进行调查。该奖项反映了NSF的法定使命，并已通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

DNA, the carrier of genetic information in biology, is increasingly being utilized for non-biological applications. The two strands that link together (hybridize) to form the twisted-shaped genetic material are now designed to link in different ways to form non-biological nanostructures. The precise assembly of nucleic acids through hybridization has revolutionized the field of DNA nanochemistry because it allows one to use simple base-pairing rules to design complex three-dimensional structures. With support from the Macromolecular, Supramolecular and Nanochemistry (MSN) Program of the Division of Chemistry, Professor Khalid Salaita of Emory University is developing increased binding strength and specificity of long strands of DNA to form nanostructures by leveraging the ability to form multiple bonds that reinforce each other. The project focuses on spatially patterned short strands of complementary DNA that function cooperatively to bind a target nucleic acid. Boosting the strength and specificity of targeted DNA binding to specific targets is critical for the application of DNA technology in sensing and diagnostic and therapeutic applications. In the course of conducting this research, graduate and undergraduate students are trained in DNA nanotechnology. K-12 students gain summer research experience and research results are incorporated into science demonstrations and video clips for the general public. The specific goal of this project is to investigate a class of multivalency where orthogonal ligand-receptor pairs are arrayed in a spatially defined manner. This type of “spatially organized heteromultivalency” is not currently employed in DNA nanostructure formation and may offer new strategies for macromolecular and supramolecular design. Professor Salaita seeks to develop synthetic methods and detailed characterization of new types of spatially patterned nucleic acid nanoparticles with enhanced binding capabilities. The hypothesis motivating the effort is that spatial organization of oligonucleotides displayed on the particle surface may lead to a substantial enhancement in the affinity and specificity of binding to a complementary nucleic acid target. An objective of the work is to develop the methodology to spatially pattern nucleic acids on the surface of gold nanoparticles. The binding affinity and specificity of patterned particles will be tested as a function of total segment number, segment density, and molecular flexibility of segments. Another objective is to create patterned liposomal particles. The impact of patterning geometry and anchoring chemistry will be investigated by measuring the full thermodynamic binding constants for these constructs.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.