Science breakthrough! Development without CRISPR efficient mitochondrial gene editor!

Posted by on July 13, 2020 9:39 pm
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Science breakthrough! Development without CRISPR efficient mitochondrial gene editor!

2020 7 November 14 hearing /Bio ValleyBIOON /–in a study recently published in Nature on a breakthrough research on A bacterial cytidine deaminase toxin contains CRISPR-free mitochondrial base editing, the researchers will sword into a plow, will be abacteriatoxin-into a genome editing tool, this is the first time can be the cells”power plant”mitochondrial DNA for a precise change. The tool in the body cells of laboratory experiments played a role, it may open a door to new research the door-and the future of dozens of difficult to treat by the mitochondrial DNA (mtDNA)mutations cause the disease to new therapies. These rare diseases, including Lebergeneticof the optic nerve lesions and fatal infant myocardial disease, the overall incidence of about 1 / 4000 to. So far, these disease research has been hampered, in part because there is no way in the mouse strains, the replication of this mutation.

University of Southern California medicineGeneticmathematician Joseph Hacia said that the new DNA editor”very innovative and pioneering”it.” It is possible in mice plays a role, and I hope it will have therapeutic significance.”

Image Source: ANGELA GAO

thousands of mitochondria present in most human cells, each mitochondria have their own genes, these mitochondria may be caused by thebacteriaevolved. Researchers in correct the cause of the mitochondrial disease of genetic defects in almost no progress, and many of the disease is by”point mutation”caused. In this mutation, a single DNA bases–adenine, cytosine, thymine or guanine-is a destruction of the desired protein or damage the activity of base substituted. Mitochondrial gene editing face a difficult is, the most famous of the genomic editor CRISPR, a key component is too large, resulting in the inability to enter the mitochondria; and the other to be able to reach the mtDNA genome editor was unable to precisely correct the point mutation.

the new study in the development of this new tool combines the CRISPR characteristics and a method called transcription activator-like effectors(TALEs)of the old technology, the three team together to create this new tool.” Makes this project so interesting and, ultimately, the success of the reason is the three laboratories organic to get together, and it is science let’s get together.” Broad Institute researchers, the study corresponding author David Liu said.

cooperation the first step is Marcos de Moraes a discovery, he at the University of Washington Seattle campus, a microbiologist Joseph Mougous laboratory work. The team studied in resource-scarce cases, how bacteria secrete toxins to kill other bacteria. 2018, de Moraes stumbled upon abacteriatoxins, it helps to catalyze the cytosine is converted to uracil. (Such bases in RNA is normal, but in DNA it will be naturally converted to thymine.) More importantly, the toxin in the DNA double helix, the two chains generated on this never-before-seen mutations.

Mougous and Liu is the same as the Howard Hughes Medical Institute, HHMI’s fellows, but with David Liu is not familiar. Nevertheless, Mougous still send email to Liu, ask him if he is interested in cooperation, because Liu’s lab previously developed a cytosine-and purine-based editing techniques, this technique uses a similar enzyme Catalyst-A is called a deaminase enzyme with CRISPR technology of the two components are combined together to use. These deaminase only on single-stranded DNA play a role. CRISPR Duo includes a RNA chain, which help to unravel the double helix structure, and the deamination enzyme is transported to the single-stranded on the precise target. However, this guide RNA (gRNA)can not enter the mitochondria.

Mougous said, the two teams from the outset to recognize that the new base editor with the Liu team to develop the editor as compared to no obvious advantage.” This prompted us to look for it a favorable market.” It turns out this discovery ultimately changed the mtDNA is. Studies of mitochondrial dysfunction of the Broad Institute experts, HHMI another researcher Vamsi Mootha, also joined the cooperation.” I’m in this field has been 25 years, and this is the first time we can[manipulate the cells], and voila, a few days later, you will edit to mitochondrial DNA.”

TALE and another early in the CRISPR genome editor zinc finger nuclease can cut off the mitochondrial double-stranded DNA, and destroys them. This helps in the treatment of some mitochondrial diseases, but can not correct mtDNA point mutations. In order to manufacture a more sophisticated tool, the Liu Lab graduate student Beverly Mok the Mougous laboratory toxins derived deaminase attached in a TALE, The TALE is a protein that can enter the mitochondria, like the gRNA as to guide the complex to reach the target.

because the deamination enzyme to the mitochondria is toxic, the researchers divide it into two halves, only in the mtDNA at the target will only be together.” We must tame this beast,”Liu said. In the human cell experiment, the cytosine is converted to thymine the chance of up to 50%. Importantly, they did not find a large number of”off target”in the edit, and this can avoid gene editing may cause serious injury.

at Columbia University to study mitochondrial disease Michio Hirano was not involved in the work, he said it was a”very clever”strategy”to solve the mitochondrial field of the history of the problem”.

in the attempt to create a human mitochondrial disease cell and mouse models on the basis of the researchers will be looking for other you can modify double stranded DNAbacteriadeaminase enzyme. They also want to improve the editing efficiency, reduce off-target gene editing, in order to mtDNA bases editing of the final energy in the human tested.” We recognize that to achieve this goal there is still a long way to go,”Liu, a Professor said.” Now we have the blueprint, I hope that this field of energy and resources will use these tools and continue to improve them.” （生物谷Bioon.com）

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Published at Tue, 14 Jul 2020 01:25:22 +0000

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