Spherical Nucleic Acids (SNAs)

Figure 1

Spherical nucleic acids, or SNAs, (Figure 1) are three-dimensional conjugates consisting of densely functionalized and highly oriented nucleic acids covalently attached to the surfaces of nanoparticles.1 The cores serve two purposes – they impart the conjugate with novel chemical and physical properties, and they act as a scaffold for assembling and orienting the oligonucleotides into a dense arrangement that gives rise to many of their functional properties that distinguish them from all other forms of matter.  Recent studies have shown that one can use the gold core as a scaffold, subsequently crosslink the DNA at the base of the particle, and dissolve the gold to create a new coreless form of SNA,2 which exhibits many of the hallmark properties of the original gold nanoparticle conjugate. This includes the ability to cooperatively hybridize with complementary nucleic acids and form stronger duplexes than the same sequence of linear DNA3 and the ability to efficiently transfect cell membranes without the need for co-carriers.4 This work underscored one of the fundamental features of SNAs –  many of the properties of these nanomaterials stem from a dense layer of oriented nucleic acids and are core-independent. While most forms of nucleic acids rely on the hybridized duplex as the fundamental structural unit that determines their overall shape, SNAs can be prepared from both single- and double-stranded nucleic acids, and their orientation is determined by the shape of the inorganic core. SNA nanostructures are distinct from the “DNA origami”5 – they can be synthesized independent of nucleic acid sequence and hybridization interactions and are formed via chemical bonds, not recognition processes.

Watch the animation below to learn more about these unique nanomaterials!


Members of the Nanobiology and Biomaterials subgroups come from diverse backgrounds spanning biology, chemistry, materials science and engineering, biomedical engineering, and chemical and biological engineering. Both of these subgroups work to understand the unique biological, chemical, and physical properties of spherical nucleic acids (SNAs); the Biomaterials subgroup works to apply SNAs as programmable “artificial atoms” in novel materials synthesis schemes and the Nanobiology subgroup works to develop novel biodetection and nanotherapeutic approaches based upon these structures.

Biomaterials Subgroup. Standing (L-R): Kurinji Krishnamoorthy, Zack Urbach, Hang Xing (leader), Youngeun Kim, Kacper Skakuj, Ashlee Robison, Stacey Barnaby (leader), Jarad Mason, Andy Wang, Alex Scott, Jessie Ku, Jeff Brodin, Mike Ross, Taegon Oh, Lianne Moreau

Sitting: Janet McMillan, Eileen Seo, Lam-Kiu Fong, Mary Wang

Nanobiology Subgroup. Top Row (L-R): Adam Sanford, Shengshuang Zhu, Alex Scott, Resham Banga, Robert Stawicki

Middle Row (L-R): Isaac Larkin, Hang Xing, Monica Guan, Gokay Yamankurt, Alyssa Chinen, AJ Sprangers, Jen Ferrer, Brian Meckes, Dia Das, Jeff Brodin, Megan Anderson, Adam Ponedal

Bottom Row (L-R): Shuya Wang, Lisa Cole, Stacey Barnaby, Caroline Kusmierz



Selected References:

[1] Cutler, J. I.; Auyeung, E; Mirkin, C. A.  “Spherical Nucleic Acids.”  J. Am. Chem. Soc., 2012, 134, 1376-1391. Doi 10.1021/ja209351u

[2] Cutler, J. I.; Zhang, K.; Zheng, D.; Auyeung, E.; Prigodich, A. E.; Mirkin, C. A. “Polyvalent Nucleic Acid Nanostructures, ” J. Am. Chem. Soc., 2011, 133, 9254–9257. Doi 10.1021/ja203375n

[3] Lytton-Jean, A. K. R.; Mirkin, C. A. “A Thermodynamic Investigation into the Binding Properties of DNA Functionalized Gold Nanoparticle Probes and Molecular Fluorophore Probes,” J. Am. Chem. Soc., 2005, 127, 12754-12755. Doi 10.1021/ja052255o

[4] Rosi, N. L.; Giljohann, D. A.; Thaxton, C. S.; Lytton-Jean, A.; Han, M. S.; Mirkin, C. A. “Oligonucleotide-Modified Gold Nanoparticles for Intracellular Gene Regulation,” Science, 2006, 312, 1027-1030. Doi 10.1126/science.1125559

[5] Seeman, N. C. “An Overview of Structural DNA Nanotechnology,” Mol. Biotechnol., 2007, 37, 246-257. Doi 10.1007/s12033-007-0059-4


Recent Publications:

[1] Macfarlane, R. J.; Thaner, R. V.; Brown, K. A.; Zhang, J.; Lee, B.; Nguyen, S. T.; Mirkin, C. A. “Importance of the DNA “Bond” in Nanoparticle Crystallization,” Proc. Natl. Aca. Sci., 2014, 111, 14995-15000, Doi 10.1073/pnas.1416489111

[2] Rouge, J. L.; Hao, L.; Wu, X. A.; Briley, W. E.; Mirkin, C. A. “Spherical Nucleic Acids as a Divergent Platform for Synthesizing RNA-Nanoparticle Conjugates Through Enzymatic Ligation,” ACS Nano, 2014, 8, 8837-8843, Doi 10.1021/nn503601s

[3] Halo, T. L.; McMahon, K. M.; Angeloni, N. L.; Xu, Y.; Wang, W.; Chinen, A. B.; Malin, D.; Strekalova, E.; Cryns, V. L.; Cheng, C.; Mirkin, C. A.; Thaxton, C. S. “NanoFlares for the Detection, Isolation, and Culture of Live Tumor Cells from Human Blood,” Proc. Natl. Aca. Sci., 2014, 111, 17104-17109, Doi 10.1073/pnas.1418637111

[4] 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, Doi 10.1021/ja503010a

[5] Auyeung, E.; Li, T.I.N.G; Senesi, A.J.; Schmucker, A.L.; Pals, B.C.; Olvera de la Cruz, M.; Mirkin, C.A. “DNA-mediated nanoparticle crystallization into Wulff polyhedra,” Nature, 2014, 505, 73-77, Doi 10.1038/nature12739

[6] Macfarlane, R. J.; Jones, M. R.; Lee, B.; Auyeung, E.; Mirkin, C. A. “Topotactic Interconversion of Nanoparticle Superlattices,” Science, 2013, 341, 1222-1225, Doi 10.1126/science.1241402

[7] Choi, C. H. J.; Hao, L.; Narayan, S. P.; Auyeung, E.; Mirkin, C. A. “Mechanism for the Endocytosis of Spherical Nucleic Acid Nanoparticle Conjugates,” Proc. Natl. Aca. Sci., 2013, 110, 7625-7630, Doi 10.1073/pnas.1305804110

[8] Zhang, C.; Macfarlane, R. J.; Young, K. L.; Choi, C. H. J.; Hao, L.; Auyeung, E.; Liu, G.; Zhou, X.; Mirkin, C. A. “A General Approach to DNA-Programmable Atom Equivalents,” Nature Materials, 2013, 12, 741-746, Doi 10.1038/nmat3647

[9] Jensen, S. A.; Day, E. S.; Ko, C. H.; Hurley, L. A.; Luciano, J. P.; Kouri, F. M.; Merkel, T. J.; Luthi, A. J.; Patel, P. C.; Cutler, J. I.; Daniel, W. L.; Scott, A. W.; Rotz, M. W.; Meade, T. J.; Giljohann, D. A.; Mirkin, C. A.; Stegh, A. H. “Spherical Nucleic Acid Nanoparticle Conjugates as an RNAi-Based Therapy for Glioblastoma,” Science Trans. Med., 2013, 5, 209ra152, Doi 10.1126/scitranslmed.3006839, PMCID: PMC4017940

[10] Auyeung, E.; Macfarlane, R. J.; Choi, C. H. J.; Cutler, J. I.; Mirkin, C. A. “Transitioning DNA-Engineered Nanoparticle Superlattices from Solution to the Solid State,” Adv. Mater.2012, 24, 5181-5186, Doi 10.1002/adma.201202069