Sperical Nucleic Acid (SNA) Nanostructures as Intracellular Probes and Gene Regulation Agents

Wednesday, November 5, 2014 - 2:00pm
Fung Auditorium, Powell-Focht Bioengineering Hall
Chad A. Mirkin, Ph.D.

George B. Rathmann Professor of Chemistry
Director of the International Institute for Nanotechnology
Northwestern University

Sperical Nucleic Acid (SNA) Nanostructures as Intracellular Probes and Gene Regulation Agents

Abstract: 
The natural defenses of biological systems for exogenous oligonucleotides, such as synthetic antisense DNA and siRNA, present many challenges for the delivery of nucleic acids in an efficient, non-toxic, and non-immunogenic fashion. Indeed, because nucleic acids are negatively charged and prone to enzymatic degradation, researchers have historically relied on transfection agents such as cationic polymers, liposomes, and modified viruses to facilitate cellular entry and protect delivered biomolecules from degradation. However, each of these platforms is subject to several drawbacks, which include toxicity at high concentrations, the requirement of specialty nucleic acids to enhance stability, and severe immunogenicity. Spherical nucleic acid (SNA) gold nanoparticle conjugates (inorganic nanoparticle cores functionalized with a spherical shell of densely organized, highly oriented nucleic acids) pose one possible solution for circumventing these problems in the context of gene regulation (antisense RNAi) and immunomodulatory pathways. Remarkably, these highly negatively charged SNA structures do not require cationic transfection agents or additional particle surface modifications and naturally enter all cell lines tested to date (over 50, including primary cells). Further work has shown the cellular uptake of these particles to be dependent upon DNA surface density: higher densities lead to higher levels of particle uptake. The high-density polyvalent nucleic acid surface layer engages scavenger receptors from the cells that facilitate endocytosis. Moreover, the ion cloud associated with the high-density oligonucleotide shell, combined with steric inhibition at the surface of the particles, inhibits enzymatic nucleic acid degradation and activation of the enzymes that trigger the innate immune response of certain cells. In this talk, methods to synthesize such structures and novel applications that take advantage of the interesting properties unique to spherical and other forms of three-dimensional nucleic acids will be described.
Bio: 

Dr. Chad A. Mirkin is the Director of the International Institute for Nanotechnology, the George B. Rathmann Professor of Chemistry, Professor of Chemical and Biological Engineering, Professor of Biomedical Engineering, Professor of Materials Science & Engineering, and Professor of Medicine. He is a chemist and a world renowned nanoscience expert, who has authored over 565 manuscripts, and inventor on over 930 patent applications worldwide (246 issued). Dr. Mirkin has been recognized for his accomplishments with over 90 national and international awards. These include the Linus Pauling Medal, the $500,000 Lemelson-MIT Prize, the Raymond and Beverly Sackler Prize in the Physical Sciences, the Feynman Prize in Nanotechnology, an Honorary Degree from Nanyang Technological Univ. Singapore, the Lee Kuan Yew Distinguished Visitor to Singapore, and the ACS Award for Creative Invention. He is a Member of the President's Council of Advisors on Science & Technology (PCAST, Obama Administration), and one of only 15 scientists, engineers, and medical doctors to be elected to all three US National Academies (the Institute of Medicine, the Natl. Academy of Sciences, and the Natl. Academy of Engineering). He is also a Fellow of the American Academy of Arts and Sciences. He is the founding editor of the journal Small and the founder of three companies, Nanosphere, Inc., AuraSense, LLC, and AuraSense Therapeutics, LLC. Dr. Mirkin holds a B.S. degree from Dickinson College and a Ph.D. degree from Penn State. He was an NSF Postdoc at MIT prior to becoming a Professor at Northwestern in 1991.