References and Papers

SNA™ technology originated in the lab of Professor Chad A. Mirkin at the Northwestern University International Institute for Nanotechnology. Papers associated with the technology’s mechanism of action, effects in various tissues and cells and biological applications are listed in key references.

Key References:

Rosi NL, Giljohann DA, Thaxton CS, Lytton-Jean A, Han MS, Mirkin CA. Oligonucleotide-Modified Gold Nanoparticles for Intracellular Gene Regulation. Science. 2006 312:1027-1030.
Patel PC, Giljohann DA, Daniel WL, Zheng D, Prigodich AE, Mirkin CA. Scavenger Receptors Mediate Cellular Uptake of Polyvalent Oligonucleotide-Functionalized Gold Nanoparticles. Bioconju. Chem. 2010 21:2250-2256.
Zheng D, Giljohann DA, Chen DL, Massich MD, Wang XQ, Iordanov H, Mirkin CA, Paller AS. Topical Delivery of siRNA-based Spherical Nucleic Acid Nanoparticle Conjugates for Gene Regulation. Proc. Natl. Acad. Sci. USA. 2012 109:11975-80.
Choi CHJ, Hao L, Narayan SP, Auyeung E, Mirkin CA. Mechanism for the Endocytosis of Spherical Nucleic Acid Nanoparticle Conjugates. Proc. Natl. Acad. Sci. USA. 2013 110(19):7625-7630.
Radovic-Moreno AF, Chernyak N, Mader CC, Nallagatla S, Kang RS, Hao L, Walker DA, Halo TL, Merkel TJ, Rische CH, Anantatmula S, Burkhart M, Mirkin CA, Gryaznov SM. Immunomodulatory Spherical Nucleic Acids. Proc. Natl. Acad. Sci. USA. 2015 112: 3892-3897.

Scientific Meeting Posters:

SNA Approach in the CNS

Spherical Nucleic Acids Show Increased Distribution and Longer Persistence than Linear Oligonucleotides in Rat Brain Following IT Administration. 2019 American Academy of Neurology. May 5, 2019
Nusinersen in Spherical Nucleic Acid (SNA) Format Improves Efficacy Both In Vitro in SMA Patient Fibroblasts and in Δ7 SMA Mice, and Reduces Toxicity in Mice Cure SMA. June 14, 2018

SNA Approach in Immuno-Oncology

Safety and Preliminary Efficacy of Intratumoral Cavrotolimod (AST-008), a Spherical Nucleic Acid TLR9 Agonist, in Combination With Pembrolizumab in Patients With Advanced Solid Tumors - (poster - PDF) Annual Meeting of the Society for Immunotherapy of Cancer. November 9, 2020
AST-008: A Novel Approach to TLR9 Agonism with PD-1 Blockade for Anti-PD-1 Refractory Merkel Cell Carcinoma (MCC) and Cutaneous Squamous Cell Carcinoma (CSCC) - (poster - PDF) 2020 Annual Meeting of the American Society of Clinical Oncology. June 1, 2020
AST-008: A Novel Approach to TLR9 Agonism with PD-1 Blockade for Anti-PD-1 Refractory Merkel Cell Carcinoma (MCC) and Cutaneous Squamous Cell Carcinoma (CSCC) - (audio - MPA) 2020 Annual Meeting of the American Society of Clinical Oncology. June 1, 2020
AST-008, a TLR9 agonist spherical nucleic acid, activated NK cells, T cells, and cytokines in healthy subjects in a Phase 1 clinical trial. American Association for Cancer Research. April 01, 2019
A Phase 1 Study of the Safety, Pharmacokinetics and Pharmacodynamics of AST-008, a TLR9 Agonist Spherical Nucleic Acid, in Healthy Subjects. EORTC-NCI-AACR (ENA) Molecular Targets and Cancer Therapeutics Symposium. November 13, 2018
Spherical Nucleic Acid (SNA) TLR9 Agonists Induce Long-Term Tumor-Specific Immune Responses In Synergy With PD-1 Checkpoint Inhibition. Society for Immunotherapy of Cancer. November 09, 2018

Selected Peer Reviewed Publications:

Wang S.; Qin L.; Yamankurt G.; Skakuj K.; Huang Z.; Chen P. C.; Dominguez D.; Lee A.; Zhang B.; Mirkin C. A. Rational vaccinology with spherical nucleic acids. Proc. Natl. Acad. Sci. USA., 2019 116(21): 10473-10481.
Yamankurt, G.; Berns, E. J.; Xue, A.; Lee, A.; Bagheri, N.; Mrksich, M.; Mirkin, C. A. Exploration of the Nanomedicine-design Space with High-Throughput Screening and Machine Learning. Nature Biomedical Engineering 2019, 3, 318-327.
Ferrer, J. R.; Wertheim, J. A.; Mirkin, C. A. Dual Toll-like Receptor Targeting Liposomal Spherical Nucleic Acids. Bioconjugate Chemistry, 2019, 30, 944-951.
Meckes, B.; Banga, R. J.; Nguyen, S. T.; Mirkin, C. A. Enhancing the Stability and Immunomodulatory Activity of Liposomal Spherical Nucleic Acids through Lipid-Tail DNA Modifications. Small, 2018, 14, 1702909.
Li, H.; Zhang, B.; Lu, X.; Tan, X.; Jia, F.; Xiao, Y.; Cheng, Z.; Li, Y.; Silva D. O.; Schrekker, H. S.; Zhang, K.; Mirkin, C. A. Molecular Spherical Nucleic Acids. Proc. Natl. Acad. Sci. USA., 2018 115(17): 4340–4344.
Skakuj, K.; Wang, Shuya; Qin, L.; Lee, A.; Zhang, B.; Mirkin, C. A. Conjugation Chemistry Dependent T-Cell Activation with Spherical Nucleic Acids. J. Am. Chem. Soc., 2018, 140, 1227-1230.
Krishnamoorthy, K.; Hoffman, K.; Kewalramani, S.; Brodin, J. D.; Moreau, L. M.; Mirkin, C. A.; Olvera da la Cruz, M.; Bedzyk, M. J. Defining the Structure of a Protein-Spherical Nucleic Acid Conjugate and its Counterionic Cloud. ACS Central Science 2018, 4, 378-386.
Fong L.-K.; Wang, Z.; Schatz, G. C.; Luijten, E.; Mirkin, C. A. The Role of Structural Enthalpy in Spherical Nucleic Acid Hybridization. J. Am. Chem. Soc., 2018, 140, 6226-6230.
Hayes, O. G.; McMillan, J. R.; Lee, B.; Mirkin, C. A. DNA-Encoded Protein Janus Nanoparticles. J. Am. Chem. Soc., 2018, 140, 9269-9274.
Yue, J.; Pallares, R. M.; Cole, L. E.; Coughlin, E. E.; Mirkin, C. A.; Lee, A.; Odom, T. W. Smaller CpG-Conjugated Gold Nanoconstructs Achieve Higher Targeting Specificity of Immune Activation. ACS Applied Materials & Interfaces 2018, 10, 21920-21926.
Guan, C.; Chernyak, N.; Dominguez, D.; Cole, L.; Zhang, B.; Mirkin, C. A. RNA-Based Immunostimulatory Liposomal Spherical Nucleic Acids as Potent TLR7/8 Modulators. Small, 2018, 14, 1803284.
Zhu, S.; Xing, H.; Gordiichuk, P.; Park, J.; Mirkin, C. A. PLGA Spherical Nucleic Acids. Adv Mater, 2018, 30(22).
Lewandowski KT, Thiede R, Guido N, Daniel WL, Kang R, Guerrero-Zayas MI, Seeger MA, Wang XQ, Giljohann DA, Paller AS. Topically Delivered Tumor Necrosis Factor-α–Targeted Gene Regulation for Psoriasis. J. Invest. Dermatol. 2017 137: 2027-2030
Sita, T. L.; Kouri, F. M.; Hurley, L. A.; Merkel, T. J.; Chalastanis, A.; May, J. L.; Ghelfi, S. T.; Cole, L. E.; Cayton, T. C.; Barnaby, S. N.; Sprangers, A. J.; Savalia, N.; James, C. D.; Lee, A.; Mirkin, C. A.; Stegh, A. H. Dual Bioluminescence and Near-infrared Fluorescence Monitoring to Evaluate Spherical Nucleic Acid Nanoconjugate Activity In Vivo. Proc. Natl. Acad. Sci. USA., 2017, 114, 4129-4134.
Sprangers, A. J.; Hao, L.; Banga, R. J.; Mirkin, C. A. Liposomal Spherical Nucleic Acids for Regulating Long Noncoding RNAs in the Nucleus. Small, 2017, 13, 1602753.
Chinen, A. B.; Guan, C. M.; Ko, C. H.; Mirkin, C. A. The Impact of Protein Corona Formation on the Macrophage Cellular Uptake and Biodistribution of Spherical Nucleic Acids. Small, 2017, 13, 1603847.
Banga, R. J.; Meckes, B. Narayan, S. P.; Sprangers, A. J.; Nguyen, S. T.; Mirkin, C. A Cross-Linked Micellar Spherical Nucleic Acids from Thermoresponsive Templates. J. Am. Chem. Soc., 2017, 139, 4278-4281.
Banga, R. J.; Krovi, S. A.; Narayan, S. P.; Sprangers, A. J.; Liu, G.; Mirkin, C. A.; Nguyen, S. T. Drug-Loaded Polymeric Spherical Nucleic Acids: Enhancing Colloidal Stability and Cellular Uptake of Polymeric Nanoparticles through DNA Surface-Functionalization. Biomacromolecules 2017, 18, 483-489.
Barnaby, S. N.; Perelman, G. A.; Kohlstedt, K. L.; Chinen, A. B.; Schatz, G. C.; Mirkin, C. A. Design Considerations for RNA Spherical Nucleic Acids (SNAs). Bioconjugate Chemistry, 2016, 27, 2124-2131.
Wang, X.; Hao, L.; Bu, H.-F.; Scott A. W.; Tian K.; Liu, F.; De Plaen, I. G.; Liu, Y.; Mirkin, C. A.; Tan, X.-D. Spherical Nucleic Acid Targeting MicroRNA-99b Enhances Intestinal MFG-E8 Gene Expression and Restores Enterocyte Migration in Lipopolysacchardie-induced Septic Mice. Scientific Reports 2016, 6, 31687.
Chinen, A. B.; Ferrer, J. R.; Merkel, T. J.; Mirkin, C. A. Relationships Between Poly(ethylene glycol) Modifications on RNA-Spherical Nucleic Acid Conjugates and Cellular Uptake and Circulation Time. Bioconjugate Chemistry, 2016, 27, 2715-2721.
Radovic-Moreno AF, Chernyak N, Mader CC, Nallagatla S, Kang RS, Hao L, Walker DA, Halo TL, Merkel TJ, Rische CH, Anantatmula S, Burkhart M, Mirkin CA, Gryaznov SM. Immunomodulatory Spherical Nucleic Acids. Proc. Natl. Acad. Sci. USA. 2015 112: 3892-3897.
Narayan, S. P.; Choi, C. H. J.; Hao, L.; Calabrese, C. M.; Auyeung, E.; Zhang, C. Goor, O. J. G. M.; Mirkin, C. A. The Sequence-Specific Cellular Uptake of Spherical Nucleic Acid Nanoparticle Conjugates. Small, 2015, 11, 4173-4182.
Randeria, P. S.; Jones, M. R.; Kohlstedt, K. L.; Banga, R. J.; Olvera de la Cruz, M.; Schatz, G. C.; Mirkin, C. A. What Controls the Hybridization Thermodynamics of Spherical Nucleic Acids? J. Am. Chem. Soc., 2015, 137, 3486-3489.
Randeria, P. S.; Seeger, M. A.; Wang, X. Q.; Wilson, H.; Shipp, D.; Mirkin, C. A.; Paller, A. S. siRNA-based Spherical Nucleic Acids Reverse Impaired Wound Healing in Diabetic Mice by GM3 Synthase Knockdown. Proc. Natl. Acad. Sci. USA., 2015, 112, 5573-5578.
Rouge, J. L.; Sita, T. L.; Hao, L.; Kouri, F. M.; Briley, W. E.; Stegh, A. H.; Mirkin, C. A. Ribozyme-Spherical Nucleic Acids. J. Am. Chem. Soc., 2015, 137, 10528-10531.
Zhang, C.; Hao, L.; Calabrese, C. M.; Zhou, Y.; Choi, C. H. J.; Xing, H.; Mirkin, C. A. Biodegradable DNA-brush Block Copolymer Spherical Nucleic Acids Enable Transfection Agent-Free Intracellular Gene Regulation. Small, 2015 11(40):5360-8.
Kouri, F. M.; Hurley, L. A.; Daniel, W. L.; Day, E. S.; Hua, Y.; Hao, L.; Peng, C. Y.; Merkel, T.; Queisser, M. A.; Ritner, C.; Zhang, H.; James, C. D.; Sznajder, J. I.; Chin, L.; Giljohann, D. A.; Kessler, J. A.; Peter, M. E.; Mirkin, C. A.; Stegh, A. H. miR-182 integrates apoptosis, growth and differentiation programs in Glioblastoma Genes and Development, 2015, 29, 732-745.
Calabrese, C. M.; Merkel, T. J.; Briley, W. E.; Randeria, P. S.; Narayan, S. P.; Rouge, J. L.; Walker, D. A.; Scott, A. W.; Mirkin, C. A. Biocompatible Infinite-Coordination-Polymer Nanoparticle-Nucleic Acid Conjugates for Antisense Gene Regulation. Angew Chem. Int. Ed., 2014, 54, 476-480.
Barnaby, S. N.; Lee, A.; Mirkin, C. A. Probing the Inherent Stability of siRNA Immobilized on Nanoparticle Constructs. Proc. Natl. Aca. Sci., 2014, 111, 9739-9744.
Chinen, A. B.; Guan, C. M.; Mirkin, C. A. Spherical Nucleic Acid Nanoparticle Conjugates Enhance G-Quadruplex Formation and Increase Serum Protein Interactions. Angew. Chem. Int. Ed., 2014, 54, 527-531.
Banga RJ, Chernyak N, Narayan SP, Nguyen ST, Mirkin CA. Liposomal Spherical Nucleic Acids. J. Am. Chem. Soc. 2014 136: 9866-9869.
Wu, X. A.; Choi, C. H. J.; Zhang, C.; Hao, L.; Mirkin, C. A. Intracellular Fate of Spherical Nucleic Acid Nanoparticle Conjugates J. Am. Chem. Soc., 2014, 136, 7726-7733.
Alhasan, A. H.; Patel, P. C.; Choi, C. H. J.; Mirkin, C. A. Exosome Encased Spherical Nucleic Acid Gold Nanoparticle Conjugates as Potent MicroRNA Regulation Agents. Small, 2014, 10, 186-192.
Jensen SA, Day ES, Ko CH, Hurley LA, Luciano JP, Kouri FM, Merkel TJ, Luthi AJ, Patel PC, Cutler JI, Daniel WL, Scott AW, Rotz MW, Meade TJ, Giljohann DA, Mirkin CA, Stegh AH. Spherical Nucleic Acid Nanoparticle Conjugates as an RNAi-Based Therapy for Glioblastoma. Sci. Transl. Med. 5, 209ra152 (2013).
Choi CHJ, Hao L, Narayan SP, Auyeung E, Mirkin CA. Mechanism for the Endocytosis of Spherical Nucleic Acid Nanoparticle Conjugates. Proc. Natl. Acad. Sci. USA. 2013 110(19):7625-7630.
Kewalramani, S; Zwanikken, J. W.; Macfarlane, R. J.; Leung, C. Y.; Olvera de la Cruz, M; Mirkin, C. A.; Bedzyk, M. J. Counterion Distribution Surrounding Spherical Nucleic AcidAu Nanoparticle Conjugates (SNA-AuNPs) Probed by Small-Angle X-Ray Scattering. ACS Nano, 2013, 7, 11301-11309.
Walter, S. R.; Young, K. L.; Holland, J. G.; Gieseck, R. L.; Mirkin, C. A.; Geiger, F. M. Counting the Number of Magnesium Ions Bound to The Surface-immobilized Thymine Oligonucleotides That Comprise Spherical Nucleic Acids. J. Am. Chem. Soc., 2013, 135, 17339-17348.
Zhang K, Hao L, Hurst SJ, Mirkin CA. Antibody-Linked Spherical Nucleic Acids for Cellular Targeting. J. Am. Chem. Soc. 2012 134:16488-16491.
Zheng D, Giljohann DA, Chen DL, Massich MD, Wang XQ, Iordanov H, Mirkin CA, Paller AS. Topical Delivery of siRNA-based Spherical Nucleic Acid Nanoparticle Conjugates for Gene Regulation. Proc. Natl. Acad. Sci. USA. 2012 109:11975-80.
Young KL, Scott AW, Hao L, Mirkin SE, Liu G, Mirkin CA. Hollow Spherical Nucleic Acids for Intracellular Gene Regulation Based upon Biocompatible Silica Shells. Nano Lett. 2012 12:3867-71.
Cutler JI, Auyeung E, Mirkin CA. Spherical Nucleic Acids. J. Am. Chem. Soc. 2012 134:1376-1391.
Zhang XQ, Xu XY, Lam R, Giljohann DA, Ho D, Mirkin CA. Strategy for Increasing Drug Solubility and Efficacy through Covalent Attachment to Polyvalent DNA - Nanoparticle Conjugates. ACS Nano. 2011 5:6962-6970.
Hao LL, Patel PC, Alhasan AH, Giljohann DA, Mirkin CA. Nucleic Acid-Gold Nanoparticle Conjugates as Mimics of microRNA. Small. 2011 7:3158-3162.
Patel PC, Hao LL, Yeung WS, Mirkin CA. Duplex End Breathing Determines Serum Stability and Intracellular Potency of siRNA-Au NPs. Mol. Pharmaceutics. 2011 8:1285-1291.
Cutler JI, Zhang K, Zheng D, Auyeung E, Prigodich AE, Mirkin CA. Polyvalent Nucleic Acid Nanostructures. J. Am. Chem. Soc. 2011 133:9254-9257.
Prigodich AE, Alhasan AH, Mirkin CA. Selective Enhancement of Nucleases by Polyvalent DNA-Functionalized Gold Nanoparticles. J. Am. Chem. Soc. 2011 133:2120-2123.
Rink JS, McMahon KM, Chen X, Mirkin CA, Thaxton CS, Kaufman DB. Transfection of Pancreatic Islets Using Polyvalent DNA-functionalized Gold Nanoparticles. Surgery 2010 148:335-345.
Patel PC, Giljohann DA, Daniel WL, Zheng D, Prigodich AE, Mirkin CA. Scavenger Receptors Mediate Cellular Uptake of Polyvalent Oligonucleotide-Functionalized Gold Nanoparticles. Bioconju. Chem. 2010 21:2250-2256.
Massich MD, Giljohann DA, Schmucker AL, Patel PC, Mirkin CA. Cellular Response of Polyvalent Oligonucleotide-Gold Nanoparticle Conjugates. ACS Nano 2010 4:5641-5646.
Giljohann DA, Seferos DS, Massich MD, Daniel WL, Patel PC, Mirkin CA. Gold Nanoparticles for Biology and Medicine. Angew. Chem. Int. Ed. 2010 49:3280-3294.
Seferos DS, Prigodich AE, Giljohann DA, Patel PC, Mirkin CA. Polyvalent DNA Nanoparticle Conjugates Stabilize Nucleic Acids. Nano Lett. 2009 1:308-311.
Giljohann DA, Seferos DS, Prigodich AE, Patel PC, Mirkin CA. Gene Regulation with Polyvalent siRNA-Nanoparticle Conjugates. J. Am. Chem. Soc. 2009 131:2072-2073.
Dhar S, Daniel WL, Giljohann DA, Mirkin CA, Lippard, SJ. Polyvalent Oligonucleotide Gold Nanoparticle Conjugates as Delivery Vehicles for Platinum (IV) Warheads. J. Am. Chem. Soc. 2009 131:14652-14653.
Patel PC, Giljohann DA, Seferos DS, Mirkin CA. Peptide Antisense Nanoparticles. Proc. Natl. Acad. Sci. USA. 2008 105:17222-17226.
Seferos DS, Giljohann DA, Rosi NL, Mirkin CA. Locked Nucleic Acid-Nanoparticle Conjugates. ChemBioChem. 2007 8:1230-1232.
Giljohann DA, Seferos DS, Patel PC, Millstone JE, Rosi NL, Mirkin CA. Oligonucleotide Loading Determines Cellular Uptake of DNA-Modified Nanoparticles. Nano Lett. 2007 7:3818-3821.
Rosi NL, Giljohann DA, Thaxton CS, Lytton-Jean A, Han MS, Mirkin CA. Oligonucleotide-Modified Gold Nanoparticles for Intracellular Gene Regulation. Science. 2006 312:1027-1030.