Optogenetics involves engineering cells to make them light-responsive and then using a laser to control their activity—whether in a dish or a live animal. As a research tool, optogenetics is unquestionably powerful. But the technique requires genetic manipulation, which makes it less favorable for certain clinical uses.
“[Optogenetics] is super cool for animal work,” says Marta Cerruti, who studies biosynthetic interfaces at McGill University in Montreal, “but I think it would be more easily ethically approved” to control cells if it didn’t include genetic tinkering. In devising a new technique involving gold nanorods, biochemical engineer Zhou Nie of Hunan University in China and colleagues were able to control cells with light but without genetic manipulation. “That’s what I thought was really interesting,” says Cerruti.
Nie knew gold nanorods had potential. These nanometer-sized particles heat up when irradiated with near-infrared light, and this photothermal response is already being explored for, among other things, light-controlled drug release for cancer therapy. Nie and colleagues decided to use the same approach, but instead of loading their nanorods with drugs, they packed them with double-stranded DNA.
The tail of one strand is fused to the gold particle. The other strand, when released from its gold-bound sister, is designed to bind and activate a particular cell-surface receptor. After delivering the rods to cultured cells or injecting them into animals, the particles are hit with infrared light, which heats and denatures the double helix, releasing the unfused strand to do its work.
In proof-of-principle experiments, Nie’s team loaded nanorods with a DNA sequence designed to activate the MET protein, a receptor present on certain stem and progenitor cells that drives cell migration and proliferation, among other processes. After showing that infrared irradiation of the rods induced MET signaling as well as migration and proliferation in cultured cells, the researchers injected the nanorods into the leg muscles of live mice that had been injured with liquid nitrogen. Because infrared light has a slightly deeper tissue penetration than the blue light commonly used for optogenetics, the researchers were able to use external lasers to activate the nanorods, which were approximately 5 mm below the skin. Simply focusing a laser beam at the animals’ damaged limbs stimulated the production of new muscle cells. (Nano Lett, 19: 2603−13, 2019)
Ruth Williams is a freelance journalist based in Connecticut. Email her at email@example.com or find her on Twitter @rooph.
|Cell manipulation technique||How it works||In vitro and in vivo use?||Genetic manipulation needed?||Cell types|
|Optogenetics||A light-sensitive ion channel from green algae, archaea, or bacteria is expressed on the surface of an animal cell. Exposure to light allows ions to flow into the cell, activating it.|
|Aptamer-coated nanorods||Gold nanorods are coated with a receptor-specific DNA strand kept inert via hybridization to a complimentary sequence. Infrared light heats the nanorods, melting the DNA and releasing the receptor-targeting strand to induce downstream signaling.||Yes||No||MET-expressing cells tested so far, but in principle any cell type can be targeted with a custom DNA strand|