Gene regulation using spherical nucleic acids to treat skin disorders

Thomas R. Holmes, Amy S. Paller*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations


Spherical nucleic acids (SNAs) are nanostructures consisting of nucleic acids in a spherical configuration, often around a nanoparticle core. SNAs are advantageous as gene-regulating agents compared to conventional gene therapy owing to their low toxicity, enhanced stability, uptake by virtually any cell, and ability to penetrate the epidermal barrier. In this review we: (i) describe the production, structure and properties of SNAs; (ii) detail the mechanism of SNA uptake in keratinocytes, regulated by scavenger receptors; and (iii) report how SNAs have been topically applied and intralesionally injected for skin disorders. Specialized SNAs called nanoflares can be topically applied for gene-based diagnosis (scar vs. normal tissue). Topical SNAs directed against TNFα and interleukin-17A receptor reversed psoriasis-like disease in mouse models and have been tested in Phase 1 human trials. Furthermore, SNAs targeting ganglioside GM3 synthase accelerate wound healing in diabetic mouse models. Most recently, SNAs targeting toll-like receptor 9 are being used in Phase 2 human trials via intratumoral injection to induce immune responses in Merkel cell and cutaneous squamous cell carcinoma. Overall, SNAs are a valuable tool in bench-top and clinical research, and their advantageous properties, including penetration into the epidermis after topical delivery, provide new opportunities for targeted therapies.

Original languageEnglish (US)
Article number360
Pages (from-to)1-19
Number of pages19
Issue number11
StatePublished - Nov 2020


  • Diabetes
  • Gene therapy
  • Nanoparticles
  • Psoriasis
  • Skin cancer
  • Spherical nucleic acids
  • Wound healing

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science


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