Curated Optogenetic Publication Database

Abstract: Gene delivery is fundamentally crucial for the genetic manipulation of stem cells. Here, we present a straightforward approach to create a library of charge-neutralized polyethylenimine (PEI)-lipid nanoparticles designed for stem cell transfection. These lipid nanoparticles were formulated using small, branched PEI and lipidic anhydrides. Remarkably, over 15% of the lipid nanoparticles demonstrated high transfection efficiency across various cell types, surpassing the efficiency of both Lipofectamine 2000 and FuGENE HD. A structure-activity analysis indicated that the length and ratio of hydrophobic alkyl substitutions were critical parameters for efficient gene delivery. Notably, the transfection efficiency was higher than that of the original cation PEI. Our optimized PEI-lipid system enabled highly effective plasmid DNA delivery and successfully co-transferred two plasmid DNAs into difficult-to-transfect human embryonic stem cells (hESCs), facilitating optogenetic manipulation within these cells.

Abstract: Photoactivated proteins controlled by optogenetic tools have broad application prospects in cell biology, neuroscience, and brain science. However, due to the narrow excitation wavelength width and the inflexibility of spatiotemporal operations, conventional sources such as visible light severely limit the further application of optogenetics. In this work, a femtosecond laser-operated system based on the optogenetic application was designed to address these limitations. The interaction between the photoreceptor and its partner protein can be triggered by a wavelength-tunable femtosecond laser. The results indicated that this process can be used to accurately manipulate optogenetic proteins in cells, which met spectral flexibility (700–1040 nm) and operational flexibility in time and space (a single cell to multiple cells). To demonstrate the practical applications of this process, the apoptotic signaling pathway of cancer cells was taken as an example. We believe that this wavelength-tunable femtosecond laser system will promote the development of optogenetics, making optics and even physics more powerful tools in biology.

Abstract: In vivo the application of optogenetic manipulation in deep tissue is seriously obstructed by the limited penetration depth of visible light that is continually applied to activate a photoactuator. Herein, we designed a versatile upconversion optogenetic nanosystem based on a blue-light-mediated heterodimerization module and rare-earth upconversion nanoparticles (UCNs). The UCNs worked as a nanotransducer to convert external deep-tissue-penetrating near-infrared (NIR) light to local blue light to noninvasively activate photoreceptors for optogenetic manipulation in vivo. In this, we demonstrated that deeply penetrating NIR light could be used to control the apoptotic signaling pathway of cancer cells in both mammalian cells and mice by UCNs. We believe that this interesting NIR-light-responsive upconversion optogenetic nanotechnology has significant application potentials for both basic research and clinical applications in vivo.