Near-Infrared Optogenetic Genome Engineering Based on Photon-Upconversion Hydrogels

Angew Chem Int Ed Engl. 2019 Dec 2;58(49):17827-17833. doi: 10.1002/anie.201911025. Epub 2019 Oct 21.


Photon upconversion (UC) from near-infrared (NIR) light to visible light has enabled optogenetic manipulations in deep tissues. However, materials for NIR optogenetics have been limited to inorganic UC nanoparticles. Herein, NIR-light-triggered optogenetics using biocompatible, organic TTA-UC hydrogels is reported. To achieve triplet sensitization even in highly viscous hydrogel matrices, a NIR-absorbing complex is covalently linked with energy-pooling acceptor chromophores, which significantly elongates the donor triplet lifetime. The donor and acceptor are solubilized in hydrogels formed from biocompatible Pluronic F127 micelles, and heat treatment endows the excited triplets in the hydrogel with remarkable oxygen tolerance. Combined with photoactivatable Cre recombinase technology, NIR-light stimulation successfully performs genome engineering resulting in the formation of dendritic-spine-like structures of hippocampal neurons.

Keywords: genome engineering; near-infrared light; photon upconversion; singlet-to-triplet absorption; triplet-triplet annihilation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Coordination Complexes / chemistry*
  • Fluorescent Dyes / chemistry*
  • Genome
  • Hydrogels / chemistry*
  • Infrared Rays
  • Kinetics
  • Micelles
  • Molecular Structure
  • Optogenetics / methods
  • Osmium / chemistry*
  • Oxygen / chemistry
  • Perylene / chemistry*
  • Photons
  • Poloxamer / chemistry
  • Structure-Activity Relationship
  • Thermodynamics


  • Coordination Complexes
  • Fluorescent Dyes
  • Hydrogels
  • Micelles
  • Poloxamer
  • Osmium
  • Perylene
  • Oxygen