Reducing the side-effects of CRISPR gene editing

Original image

Original image

Successfully decoding known information from a strand of DNA is, Shipman believes, the first step in a line of research that would get cells to act like a living diary.

Scientists have already used plain old DNA to encode and store all 587,287 words of War and Peace, a list of all the plant material archived in the Svalbard Seed Vault, and an OK Go music video. Two of these also inhibited the Cas9 protein most commonly used by researchers, which is adapted from the bacterium Streptococcus pyogenes and is referred to as SpyCas9.

Scientists used the CRISPR method to splice a series of five frames from the series of moving horse images.

The team included researchers in the lab of Jennifer Doudna, one of the inventors of CRISPR-Cas9 gene editing, who determined how the anti-CRISPR protein binds to the CRISPR-Cas9 complex. After looking at the genome of the new cells, researchers found the synthetic DNA containing the trotting horse was in the genetic code with 90% accuracy. This was discovered by sequencing the whole genome of mice that had previously undergone CRISPR gene editing.

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But those worries could soon be put to rest, as scientists have developed proteins that can prevent the unnecessary mutations from occurring by acting as a 'kill switch'. When viruses attack bacteria, the bacteria use this defense mechanism to cut parts of the virus's DNA and paste them inside its own DNA. "We envision a biological memory system that's much smaller and more versatile than today's technologies, which will track many events non-intrusively over time", said Dr. Seth Shipman, a postdoctoral fellow at Harvard Medical School and firs author of the paper reporting the results in the journal Nature. Storing information in living DNA is more difficult because the cells are always changing. The scientists at the New York Genome Center (NYGC) encoded then retrieved without errors a full computer operating system, an 1895 French film, "Arrival of a train at La Ciotat", a $50 Amazon gift card, a computer virus, a Pioneer plaque and a 1948 study by information theorist Claude Shannon. The researchers chopped up each frame into single-colored pixels.

Jacob Corn, one of the first authors on the study, said: 'The ability to turn Cas9 gene editing off is just as important as the ability to turn it on. 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. But what if they could coerce living cells, like large populations of bacteria, into using their own genomes as a biological hard drive to can record information that can be accessed anytime? They sequentially treated bacteria with a frame of translated DNA over the course of five days. "We don't really understand why that is", he says.

"We want to use neurons to record a molecular history of the brain through development".

"The sequential nature of CRISPR makes it an appealing system for recording events over time", Shipman said.