Gene Regulation Using Spherical Nucleic Acids to Treat Skin Disorders
Abstract
1. Introduction
2. Introduction to SNAs: Structure and Synthesis
2.1. SNA Structure
2.1.1. SNA Core
2.1.2. Oligonucleotide Attachment to SNA Core
2.1.3. Oligonucleotide Spacer Region
2.1.4. Oligonucleotide Targeting Sequence
2.1.5. Oligonucleotide Functional Additives
2.2. SNA Synthesis Using an Au-NP Core
2.3. Generation of Liposomal SNAs
3. Mechanism of SNA Cellular Uptake and Processing in Keratinocytes
4. Utility and Safety of SNAs
4.1. Advantages of SNAs
4.2. Safety of SNAs In Vitro and In Vivo
5. Using SNAs for the Detection and Treatment of Skin Disease
5.1. Diabetic Wound Healing
5.2. Nanoflares to Detect Abnormal Scar Formation
5.3. Psoriasis
5.4. Clinical Trials Using SNAs to Treat Skin Pathologies
6. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Clinical Phase; Status | Skin Disease | Target (Treatment, Dose) | Administration (Sample Size) | Primary Outcome Measure | Secondary Outcome Measures |
Pre-clinical (human 3D, mouse); Completed | Psoriasis | TNFα (L-SNA; 50 μM) | Topical, every other day for 1 week (N = 12 per group) | Psoriasis severity | Psoriatic marker expression, proliferation |
Pre-clinical (human 3D, mouse); Completed | Psoriasis | IL-17RA (L-SNA; 50 μM) | Topical, daily for 1 week (N ≥ 6 per group) | Psoriasis severity | Psoriatic marker expression, proliferation |
Pre-clinical; Completed | Impaired wound healing | GM3S (Au-NP-SNA; 50 nM) | Topical, every other day (N = 8 per group) | Wound closure | Granulation tissue, metabolic signaling |
Phase 1; Completed | Psoriasis | TNFα (AST-005) L-SNA; each subject received vehicle, 0.1%, 0.3%, and 1% | Topical, daily for 28 days (N = 15) | Adverse events | TNFα knockdown, safety, tolerability, dosing |
Phase 1; Completed | Psoriasis | IL-17RA (XCUR17) L-SNA; dosage information not available | Topical, daily for 25 days (N = 21) | Adverse events | Il-17RA knockdown, safety, tolerability, dosing, skin inflammation, psoriatic gene expression |
Phase 1; Completed | Healthy subjects | Toll-like receptor 9 (TLR9) agonist (AST-008 1) L-SNA; 2–32 mg | Subcutaneous injection, weekly for 9 weeks then every 3 weeks (N = 16) | Adverse events | Recommended dosage, immune response, cytokine/chemokine levels |
Phase 1b; Completed | Primarily advanced melanoma,Merkel cell carcinoma (MCC), cutaneous squamous cell carcinoma (cSCC) | TLR9 agonist (AST-008) L-SNA; 2–32 mg with anti-PD-1 antibody (pembrolizumab) | Subcutaneous injection, weekly for 9 weeks then once every 3 weeks (N = 20) | Dose escalation study (2–32 mg): adverse events in combination with pembrolizumab | Recommended dosage, immune response |
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Holmes, T.R.; Paller, A.S. Gene Regulation Using Spherical Nucleic Acids to Treat Skin Disorders. Pharmaceuticals 2020, 13, 360. https://doi.org/10.3390/ph13110360
Holmes TR, Paller AS. Gene Regulation Using Spherical Nucleic Acids to Treat Skin Disorders. Pharmaceuticals. 2020; 13(11):360. https://doi.org/10.3390/ph13110360
Chicago/Turabian StyleHolmes, Thomas R., and Amy S. Paller. 2020. "Gene Regulation Using Spherical Nucleic Acids to Treat Skin Disorders" Pharmaceuticals 13, no. 11: 360. https://doi.org/10.3390/ph13110360
APA StyleHolmes, T. R., & Paller, A. S. (2020). Gene Regulation Using Spherical Nucleic Acids to Treat Skin Disorders. Pharmaceuticals, 13(11), 360. https://doi.org/10.3390/ph13110360