Valency-Controlled Molecular Spherical Nucleic Acids with Tunable Biosensing Performances

Area of Science:

• Biotechnology
• Nanotechnology
• Molecular Biology

Background:

• Spherical nucleic acids (SNAs) are crucial in molecular diagnostics, therapeutics, and materials science.
• Precise control over DNA density in SNAs is essential for structure-function studies and regulating SNA properties.
• Synthesizing monodisperse SNAs with tunable valency and site-specificity remains a significant challenge.

Purpose of the Study:

• To develop a novel method for creating valency-controlled framework nucleic acid-based molecular spherical nucleic acids (FNA-mSNAs).
• To enable molecular-level investigation of how valency affects SNA properties like nuclease stability and cellular uptake.
• To demonstrate the tunable biosensing performance of heterogeneous FNA-mSNAs.

Main Methods:

• Utilized the controllability, nanometer precision, and addressable modification of framework nucleic acid (FNA) technology.
• Designed FNA-mSNAs with a valency-tunable FNA-based DNA nanocube core and a controlled number of DNA strands.
• Varied the binding site number for shell DNA strands on the DNA nanocube to achieve homogeneous FNA-mSNAs with different valencies.
• Demonstrated heterogeneous molecular SNAs with tunable valency by leveraging FNA's addressable modification.

Main Results:

• Successfully synthesized homogeneous FNA-mSNAs with easily tunable valencies by altering DNA binding sites on the FNA core.
• Investigated the impact of valency on SNA properties, including nuclease stability and cellular uptake at the molecular level.
• Created the first heterogeneous molecular SNAs with tunable valency using FNA's addressable modification capabilities.
• Showcased that the valency of heterogeneous FNA-mSNAs can effectively tune biosensing performance, including response dynamics, sensitivity, and range.

Conclusions:

• FNA-mSNAs offer a versatile platform for precisely controlling SNA structure and function at the molecular level.
• This approach facilitates in-depth studies of structure-property relationships and the development of advanced biosensors.
• FNA-mSNAs represent a significant advancement for creating functional SNAs with tailored properties for diverse biological applications.