The revolutionary CRISPR-Cas9 gene editing tool is best known for helping scientists edit a DNA chain more accurately and efficiently than ever before.
Now, researchers have shown another use of the CRISPR complex: changing which genes are expressed without altering the genome itself.
For the first time, researchers at the Salk Institute in San Diego were able to use CRISPR to activate beneficial genes in live mice suffering from muscular dystrophy, type 1 diabetes and acute kidney injury.  In more than 50% of the test cases, the animal's health improved after the CRISPR intervention, according to a study published in the journal Cell on Thursday.
Previous work had already shown that CRISPR could be used to alter gene expression in cells by a Petri dish, but the new study represents the first time the technique has worked in a living animal, the scientists said.
The feat is significant.
"We moved this technology that a big step towards human therapy," said Hsin-Kai Liao, a postdoctoral researcher at Salk and co-author of the article.
Alexis Komor, a biochemist at the University of California at San Diego who did not participate in the work, agreed. "This is a really complete study in vivo that begins to close the gap between the use of CRISPR-based tools in dish cells and their translational use," he said.
CRISPR-Cas9 has been described. Like the Swiss Army Knife of gene editing, since it performs several different functions.
To begin with, it works like a search button in your word processor. Scientists can easily program it to find a specific string of letters in a DNA sequence.
Once you find those letters, the complex transforms into a pair of molecular scissors. An enzyme, usually Cas9, binds to the chosen region and produces a breakdown of two chains in the DNA double helix.
To replace a defective gene with a functional one, scientists also connect a DNA strand to the CRISPR complex. The hope is that the cell will use the new DNA to repair the cut in its genome.
This works many times but not all the time, and can lead to accidental deletions or insertions in the genetic code.
To circumvent this danger, researchers have experimented with using a disabled version of the CRISPR-Cas9 system to deliver instructions that activate or deactivate a specific gene.
In this version of CRISPR, the Cas9 enzyme is deactivated. You can still join DNA, but you can not make a cut. Instead, it brings with it molecules that can tell the cell that it is time to activate a particular gene.
In addition to eliminating the possibility of mutations reaching the genome, other advantages of this technique are that it is impermanent and adjustable, said Juan Carlos Izpisua Belmonte, a development biologist at Salk and the principal investigator of the article.
It also mimics the process that cells already use to signal their genes to light up.
"This is very similar to what a cell normally does to activate a gene, so it is not abnormal what is happening," he said.
Scientists have been trying to use CRISPR to give orders to a cell marching at least since 2013. But it was not until now that anyone could make it work on a live animal.
The challenge, according to the scientists, was to elaborate the administration system.
Researchers often use a virus to insert new material into the cells of living animals. However, this transportation system has a size limit. It works only with relatively small molecules. The instructions that the scientists used to activate the genes in the cells of a Petri dish were too large to be transported by the virus.
To overcome this obstacle, the researchers separated the Cas9 from the instructions. They inserted the Cas9 into the cell with one virus and the marching orders with another.
It took about four years of trial and error, but they finally succeeded.
Fumiyuki Hatanaka, a post-doctoral researcher at Salk and the other first author of the article, recalled the first time he saw the physical results of his experiments. He was working with mice with weakened muscles to see if he could use the systems to activate genes that promote muscle growth.
"The first time we saw muscle change, it was very obvious from the outside," he said. . "I remember being very excited because nobody had ever shown this phenotype in an animal before."
Belmonte said that the whole lab excited.
"It was an important moment," he said.
In the following months, the research team used its system to treat mice with other ailments, such as acute kidney injury, type 1 diabetes and muscular dystrophy.
There is still much work to be done before this method can be used in human patients, however. The researchers said that the next step is to see how it works in larger animals. In addition, the security of the system must be tested repeatedly.
"Our ultimate goal is to treat the disease, so we want to make sure this technique really works," Hatanaka said.
Komor said the work is exciting, but noted that the end result would be a treatment of the disease, rather than a cure.
"Then a patient would probably require repeated treatments depending on the particular disease," he said.
The benefit, however, is that treatments can be tailored to a specific individual, the study authors said.
They also said that their technique can be used in many diseases, including Alzheimer's disease and perhaps the aging process in general.
"When you act, you try to help, not hurt," said Belmonte. "If we do not cut the genome, we do not present a problem, and that is the main advantage of this technique."
Do you love science? I make! Follow me @DeborahNetburn and "like" Los Angeles Times Science & Health on Facebook.
MORE IN SCIENCE