Biradial Spherical Nucleic Acids

Biradial Spherical Nucleic Acids for Targeted and Protected Oligonucleotide Delivery

SHORT DESCRIPTION
A liposome-based spherical nucleic acid platform that encapsulated oligonucleotides and supports targeted cellular uptake through multivalent, receptor-binding outer oligonucleotides. Prepared using a non-enzymatic manufacturing method, these SNAs are compatible with nuclease-resistant nucleotides and high-melting lipids, enabling a highly stable architecture that is ideal for targeted cell delivery.

• Chad Mirkin*, PhD
• Krishna Paranandi

NU 2023-205

IP STATUS
U.S. Patent Application Published (US 2025/0283095 A1; Application No. 19/073,709)

BACKGROUND
Intracellular delivery of oligonucleotides is limited by poor cellular entry and nuclease degradation. Nanoparticle encapsulation improves delivery but loads inefficiently and offers limited flexibility to separately control cargo protection and cell-targeting functions. 

ABSTRACT
Biradial spherical nucleic acids (SNAs) are liposome-based nanostructures that place hydrophobically functionalized oligonucleotides in both the inner and outer leaflets of a liposome core. This architecture supports more efficient core encapsulation of oligonucleotides than passive encapsulation. An electrophoresis-based extraction strategy can replace the outer oligonucleotides with a different sequence, yielding hetero-biradial particles whose interior cargo and exterior targeting ligand are selected independently. In cultured brain endothelial cells, such SNAs displaying a transferrin receptor aptamer on the exterior delivered more interior cargo oligonucleotide than conventional SNAs or control structures.

APPLICATIONS

• Intracellular delivery of nucleic acid drugs: Enhances cellular entry of oligonucleotides.

ADVANTAGES

• Improves cargo encapsulation: Incorporates oligonucleotides into the liposome core more efficiently than passive encapsulation with non-functionalized oligonucleotides.
• Oligonucleotide protection: Shields incorporated or encapsulated oligonucleotides from nuclease degradation and serum-protein destabilization.
• Targeted therapeutics and diagnostic probes: Enables exchange of outer oligonucleotides with sequences or labels designed for target binding or detection.
• SNAs compatible with nuclease-resistant nucleotides and high-melting lipids

KEYWORDS
spherical nucleic acids, SNA, oligonucleotide delivery, liposomal nanoparticles, targeted drug delivery, nucleic acid therapeutics, receptor-mediated uptake, multivalent targeting, oligonucleotide encapsulation, nuclease protection