"For eventual therapeutic applications, it is critical to be able to precisely control when and where gene editing is active".
"DNA is a great place to store information".
Using the gene editing technology CRISPR, scientists funded by the National Institutes of Health (NIH) set out to prove that any arbitrary sequential information - not just genetic information - could be encoded into a genome.
Apart from the spectacle of immortalising this already famous horse flick, researchers say the technique used here could enable living cells to become a real-time "molecular recorder", capturing unseen biological developments inside the body like a kind of organic Digital Video Recorder.
In 2016, a team from Harvard Medical School and the Wyss Institute for Biologically Inspired Engineering led George Church built the first molecular recorder based on the CRISPR system that allows cells to acquire bits of chronologically provided, DNA-encoded information to generate a memory of them in the genome of bacteria as a cell model. Researchers can use it to knock out genes in animal models to study their function, give crops new agronomic traits, synthesize microbes that produce drugs, create gene therapies to treat disease, and potentially-after some serious ethical debate-to genetically correct heritable diseases in human embryos. The researchers took advantage of the fact that the proteins always insert new genetic material upstream from the old genetic material.
"Even after six hours of effective CRISPR, inserting anti-CRISPR decreases off-target effects by more than two-fold compared to on-target effects", Shin said.
CRISPR-blocking proteins work by targeting a spot on the CRISPR-Cas9 molecule and binding with it, rendering the molecule unable to cut DNA, the team said. So, they made movies to show off DNA as an "excellent medium for archiving data" according to the paper published today in the journal Nature. Molecular recorders would gather an individual's biological data and could lead the way to improve existing methods for "generating cells for regenerative therapy, disease modeling and drug testing".
"The sequential nature of CRISPR makes it an appealing system for recording events over time", said Seth Shipman, a post-doctoral fellow at Harvard Medical School.
Over the course of five days, they sequentially treated bacteria with a frame of translated DNA. "In doing so, we push the technical limits of this information storage system and optimize strategies to minimize those limitations". Dozens of teams are developing such software, and each faces the task of keeping up with rapidly evolving science and an increasingly crowded field. Here's the GIF before the insertion into the bacteria and the reconstruction.
The five frame GIF of a horse and rider was placed into the live bacteria frame by frame. Using this method, their reconstruction was 90 percent accurate. Cas9 is a protein that cuts double chain in a particular area. He recently engineered bacteria to make coloured pictures. "One day", noted Dr. Shipman, "we may be able to follow all the developmental decisions that a differentiating neuron is taking from an early stem cell to a highly specialized type of cell in the brain, leading to a better understanding of how basic biological and developmental processes are choreographed".
CRISPR was also used to encode this image of a hand into a bacterial genome.