Nature is a major development! Develop an efficient mitochondrial DNA base editor!

!--:page title"--July 14, 2020 /PRNewswire/ -- In a ground-breaking study published recently in Nature, researchers used swords to be ploughed into a bacterial toxin into a genome-editing tool, the first time a "wire-to-the-wire dna" can be used to change the cells' dnathe tool, which has worked in laboratory experiments on human cells, could open a new door to research -- and new treatments for dozens of diseases that are difficult to treat in the future, caused by muched mitochondrial DNA (mtDNA)these rare diseases, including Leber's inherited optic neuropathy and the fatal infant cardiomyopathy, with a total incidence of about 1/4000so far, research into these diseases has been hampered, in part because there is no way to replicate the mutation in mouse lineageJoseph Hacia, a medical geneticist at the University of, said the new DNA editor was "very innovative and pioneering."", "It's likely to work in mice, and I hope it will have therapeutic implications in the coming years."" picture source: ANGELA GAO Thousands of mitochondria are present in most human cells, each with its own genes, which may have evolved from bacteriaresearchers have made little progress in correcting genetic defects that cause mitochondrial disease, many of which are caused by "point mutations."in this mutation, a single DNA base -- adenine, cytosine, thymus, or ostrich -- is replaced by a base that destroys the desired protein or impairs activityone of the difficulties faced by mitochondrial gene editing is that a key component of CRISPR, the most famous genome editor, is too large to enter the mitochondria;the new tool developed in the new study, which combines the characteristics of CRISPR with an old technique called transcription activator sub-effects (TALEs), the three teams worked together to create the new tool"The reason for this project is that the three labs come together organically, and it's science that brings us together.", said David Liu, a researcher at the Broad Institute and the study's author's first step in the collaboration was a study by Marcos de Moraes, who works in the lab of Joseph Mougous, a microbiologist at the University of Washington in Seattleteam studied how bacteria secrete toxins to kill other bacteria when resources are scarce2018, de Moraes stumbled upon a bacterial toxin that helps catalyze cytosine into a ura (this base is normal in RNA, but it naturally converts into thymus in DNA more importantly, the toxin produces this never-before-seen mutation in two chains of the double helix of DNA Mougous, like Liu, is a researcher at the Howard Hughes Medical Institute (HHMI), but is not familiar with David Liu Despite this, Mougous emailed Liu asking if he was interested in working together because Liu's lab had previously developed cytosine and niobium-based editing techniques that used a similar enzyme catalyst -- an enzyme called deaminase - combined with two components of CRISPR technology these deaminases only work on single-stranded DNA CRISPR duo includes an RNA chain that helps unlock the double helix structure and transport deaminase to an exact target on a single chain but this guided RNA (gRNA) does not enter the mitochondria Mougous says the two teams realized from the start that the new base editor had no significant advantage over the editor that Liu's team developed " this prompted us to look for a favorable market for it "It turns out that this discovery ultimately changed mtDNA," Vamsi Mootha, an expert at the Broad Institute who studies mitochondrial dysfunction , and another hHMI researcher, joined the collaboration "I've been in this field for 25 years, and this is the first time we've been able to manipulate the cells, and look, a few days later, you've edited mitochondrial DNA." " TALE and another genome editor earlier than CRISPR, zinc-finger nuclease, can cut off the mitochondria's double-stranded DNA and destroy them this helps treat some mitochondrial diseases, but does not correct mtDNA point mutations to create a more sophisticated tool, Beverly Mok, a graduate student at Liu's lab, attached the toxin-derived deaminase in the Mougous laboratory to a TALE, a protein that can enter the mitochondria and, like gRNAs, guide the complex to its target because deaminase is toxic to mitochondria, the researchers split it in half, only at the mtDNA target "We have to tame this beast," Liu said in experiments with human cells, the chances of cytosine converting to thymus are as high as 50% important, they didn't find a large number of "off-target" edits that could avoid the serious harm that gene editing could cause Michio Hirano, who studies mitochondrial disease at Columbia University, said it was a "very smart" strategy that "solves the historical problems of mitochondrial disease." trying to create cell and mouse models of human mitochondrial disease, the researchers will look for other bacterial deaminases that modify double-stranded DNA they also hope to improve editing efficiency and reduce off-target gene editing so that mtDNA base editing can eventually be tested on humans "
We recognize that there is still a long way to go to get there, " says Professor Liu "Now that we have a blueprint, I hope that the energy and resources in this area will use these tools and continue to improve them," " () !--/ewebeditor: page- !--ewebeditor: page title"--References: 1 New method to edit cell's 'powerhouse' DNA help study study y of the genetic diseases "2 a a tha iadydidine" Aminase toxin enables crispr-free mitochondrial base editing "3" Zapping mutant DNA in mitochondria treat major class of the big class of the genetic disease "4" The Tale of the TALEs 5" NovelR-derived 'base' operatingly rhad DNA or RNA, offering new ways to fix mutations !--/ewebeditor: page.