Photonic Gene Circuits by Optically Addressable siRNA-Au Nanoantennas

Abstract

The precise perturbation of gene circuits and the direct observation of signaling pathways in living cells are essential for both fundamental biology and translational medicine. Current optogenetic technology offers a new paradigm of optical control for cells; however, this technology relies on permanent genomic modifications with light-responsive genes, thus limiting dynamic reconfiguration of gene circuits. Here, we report precise control of perturbation and reconfiguration of gene circuits in living cells by optically addressable siRNA-Au nanoantennas. The siRNA-Au nanoantennas fulfill dual functions as selectively addressable optical receivers and biomolecular emitters of small interfering RNA (siRNA). Using siRNA-Au nanoantennas as optical inputs to existing circuit connections, photonic gene circuits are constructed in living cells. We show that photonic gene circuits are modular, enabling sub-circuits to be combined on-demand. Photonic gene circuits open new avenues for engineering functional gene circuits useful for fundamental bioscience, bioengineering, and medical applications.

Selective Light-Triggered Release of DNA from Gold Nanorods Switches Blood Clotting On and Off

“…In particular, external laser excitation of nanoparticles can trigger payload release [6], [7], so nanoparticles can act as handles for controlling biological processes. Gold nanorods (NRs) have gained considerable interest for therapeutic applications because they can be selectively excited where tissue is transparent to release multiple species that can impact complex processes [6], [8]–[10] so they have many advantages for controlling blood clotting.…”

RNA-guided diagnostics and therapeutics for next-generation individualized nanomedicine

“…Goldbased plasmonic nanomaterials and photothermal genetic engineering methods have been used to develop nanovectors that silence specific genes in vivo via photothermal activation of RNAi (23)(24)(25). A combination of photo-heating and near-infrared light has been used to target goldbased plasmonic nanoparticles and trigger release of gene-specific siRNAs and other classes of noncoding RNAs in a temporally and spatially defined manner (23)(24)(25).…”

“…Goldbased plasmonic nanomaterials and photothermal genetic engineering methods have been used to develop nanovectors that silence specific genes in vivo via photothermal activation of RNAi (23)(24)(25). A combination of photo-heating and near-infrared light has been used to target goldbased plasmonic nanoparticles and trigger release of gene-specific siRNAs and other classes of noncoding RNAs in a temporally and spatially defined manner (23)(24)(25). Ren et al (26) reported the development and preclinical validation of a tumor-penetrating nanocomplex that combines a tandem tumor-penetrating and membrane-translocating peptide with siRNA, which was capable of specific and highly efficient in vivo delivery of siRNA deep into the tumor parenchyma (26).…”

Photothermal Genetic Engineering

“…Chemistries beyond thiols may need to be considered for siRNA attachment to enable intensity-dependent photorelease of the payload from the gold surface. While Jain et al 24 27 provide a first demonstration of multiplexed photothermal interrogation, additional experiments will be required to eliminate the existing cross-talk between the plasmonic structures. Physical modeling of the dependence of the absorption spectra and the shape of the surface plasmon mode on the nanostructure geometry may enable computer-guided design of plasmonic nanomaterials with narrow resonances.…”

“…In this issue of ACS Nano, Lee et al 27 extend the photothermal approach for RNAi-mediated gene silencing to multistep bidirectional control of specific gene expression ( Figure 1). In this elegant study, the authors take advantage of the tunability of the longitudinal plasmon resonance wavelength in gold nanorods (GNRs), which is enabled simply by adjusting the aspect ratio.…”