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Rational Design of Spherical Nucleic Acids: Expanding Horizons for Precision Nucleic Acid Therapy.

Yu Li1,2,3, Songhan Liu4, Jun Yang1,2,3

  • 1School of Life Science, School of Interdisciplinary Science, Aerospace Center Hospital, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing 100081, P. R. China.

ACS Applied Materials & Interfaces
|March 25, 2026
PubMed
Summary

Spherical nucleic acids (SNAs) overcome limitations in nucleic acid therapy by offering enhanced stability and cellular uptake. This review details SNA design and applications for precise, targeted gene regulation in precision medicine.

Keywords:
drug deliverygene regulationlysosome-targeting chimaerasspherical nucleic acidstargeted protein degradation

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Area of Science:

  • Biotherapy
  • Nanomedicine
  • Molecular Biology

Background:

  • Nucleic acid therapy shows promise for gene-specific disease regulation but faces challenges like degradation and poor uptake.
  • Spherical nucleic acids (SNAs) present a nanoplatform solution due to their unique geometry-driven advantages.
  • SNAs offer modular flexibility, physiological stability, and efficient intracellular accumulation.

Purpose of the Study:

  • To systematically review advances in the rational design of SNAs for precision nucleic acid therapy.
  • To decipher SNA structure-function relationships to guide rational design strategies.
  • To highlight intelligent SNA strategies for precise treatment in diverse disease microenvironments.

Main Methods:

  • Systematic review of recent research on SNA design and applications.
  • Analysis of SNA structure-function relationships.
  • Exploration of intelligent SNA strategies for responsive therapies.

Main Results:

  • SNAs demonstrate functional versatility and broad engineering potential for expanding therapeutic scenarios.
  • Rational design of SNAs can overcome key challenges in nucleic acid delivery.
  • Intelligent SNA strategies enable precise treatment tailored to disease microenvironments.

Conclusions:

  • SNAs are indispensable for advancing precision nucleic acid therapeutics.
  • This review provides guidance for translating SNA-based therapies from research to clinical practice.
  • Further development of SNA design will enhance their clinical translation and therapeutic efficacy.