Plasmonics-enabled Localized Gene Delivery and Photonic Gene Circuits

Date(s) - 01/22/2013
4:00 pm

Dr. Somin Lee, NIH Ruth L. Kirschstein Post Doctoral Fellow, Lawrence Berkeley National Laboratory, Berkeley, California

Metal nanoantennas exhibiting plasmon resonances receive, focus and confine freely propagating electromagnetic fields to sub-wavelength volumes. By designing the geometry of metal nanoantennas, optical properties can tuned to the near infrared region where cells and tissues are essentially transparent. Enhanced absorption at the nano-scale can be exploited to photothermally release biomolecules, with spatial and temporal precision, for practical applications in biology and medicine.

The first part of the talk will discuss the development of DNA-Au nanoantennas and siRNA-Au nanoantennas for optical control of gene delivery. Antisense DNA and small interfering RNA (siRNA) oligonucleotides enable direct, sequence-specific silencing of genes, but alone, lack spatiotemporal manipulation. While attached to nanoantennas, oligonucleotide functionality is inactivated. When optically addressed, nanoantennas photothermally release oligonucleotides and subsequently “activate” their functionality. I demonstrate the delivery of DNA-Au nanoantennas and siRNA-Au nanoantennas into living cells. I show the localized release of oligonucleotides from nanoantennas using light as a remote trigger. I show that genes can be optically silenced with no cytotoxicity, creating opportunities in localizing gene therapy.  

The second part of the talk will discuss the construction of photonic gene circuits. Gene circuits, consisting of interconnected genes and proteins, give rise to essential cell functions. Yet many gene circuits remain incompletely understood. A major challenge is probing native gene circuits with high signal fidelity. Here, I will discuss how this limitation can be overcome by utilizing siRNA-Au nanoantennas to precisely perturb gene circuits with high signal fidelity. Using siRNA-Au nanoantennas as optical inputs to existing gene circuit connections, I demonstrate several photonic gene circuit configurations in living cells. I demonstrate that photonic gene circuits are modular, enabling sub-circuits to be combined on-demand. Photonic gene circuits open new avenues for optical deconstruction of gene circuits in cellular and multi-cellular systems biology as well as optical reconfiguration of mal-functioning gene circuits to functional gene circuits.