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#1 09-07-2018 04:53:51

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Date d'inscription: 17-12-2015
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SAN FRANCISCO Femme Nike Air Presto QS Chaussures Rouge Blanche , Sept. 20 (Xinhua) -- Researchers in the United States have identified a key region within a protein that governs how accurately the gene-editing tool known as CRISPR-Cas9 homes in on a target deoxyribonucleic acid (DNA) sequence.


CRISPR is short for Clustered Regularly Interspaced Short Palindromic Repeats and Cas9 stands for CRISPR Associated Protein.


The researchers at the University of California, Berkeley, and Massachusetts General Hospital said they have tweaked the region within the Cas9 protein to produce a hyper-accurate gene editor with the lowest level of off-target cutting to date. Identified as a master controller of DNA cutting, the protein domain known as REC3 is a target for re-engineering to further improve accuracy and to minimize the chance that CRISPR-Cas9 will edit DNA at the wrong place.


Co-first author Janice Chen Acheter Nike Air Max TN Marine Bleu Noir , a graduate student in the lab of Jennifer Doudna, the UC Berkeley professor of molecular and cell biology who was one of the first scientists to invent CRISPR-Cas9 technology, noted in a press release that "we have found that even minor alterations in the REC3 domain of Cas9 affect the differential between on- and off-target editing, which suggests that this domain is an obvious candidate for in-depth mutagenesis to improve targeting specificity."


Targeting specificity is a key consideration when doing gene therapy in humans.


Currently Homme Nike Air Max TN Chaussures Noir Blanche , scientists using CRISPR-Cas9 create a single-guide ribonucleic acid, or sgRNA, an RNA molecule that includes a chain of 20 ribonucleic acids that complements a specific 20-nucleic-acid DNA sequence they want to target, and attach it to Cas9. This guide RNA allows Cas9 to home in on the complementary DNA Air Max 97 Ultra Noir Blanche Homme Pas Cher , bind to it and cut the double stranded helix.


However, the Cas9-sgRNA complex can bind to DNA that doesn't exactly match, leading to undesirable off-target cutting.


Doudna's lab discovered in 2015 a conformational switch of Cas9 that is activated when the RNA guide and DNA target match. They found that only when the RNA and DNA match closely does the 3D structure of Cas9, in particular the conformation of the HNH nuclease domain Homme Nike Air Max 97 OG GS Chaussures Noir Et Blanche , change and activate the scissors of Cas9. But the process for sensing the nucleic acids upstream of the conformational switch remained unknown.


In the current study supported by the U.S. National Institutes of Health (NIH) and the U.S. National Science Foundation (NSF), Chen and her colleagues used a technique called single-molecule Forster resonance energy transfer (FRET) to precisely measure how the various protein domains in the Cas9-sgRNA protein complex - in particular REC3, REC2 and HNH - move when the complex binds to DNA.


The researchers uncovered that the REC3 domain is responsible for sensing the accuracy of target binding, which then signals the outward rotation of the REC2 domain to open a path for the HNH nuclease domain Homme Nike Air Max 97 Chaussures Blanche et Noir , activating the scissors. They then showed that by mutating parts of REC3, it is possible to change the specificity of the Cas9 protein so that the HNH nuclease is not activated unless the guide RNA and target DNA match is very close.


They were able to engineer an improved hyper-accurate Cas9, dubbed HypaCas9, that retains its on-target efficiency but is slightly better at discriminating between on- and off-target sites in human cells.


"If you mutate certain amino acid residues in REC3 Homme Nike Air Max 97 KPU TPU Chaussures Noir Rouge , you can tweak the balance between Cas9 on-target activity and improve specificity; we were able to find the sweet spot where there is sufficient activity at the intended target but also a large reduction in off-target events," Chen was quoted as saying in the news release from UC Berkeley.


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TOKYO, Sept. 21 (Xinhua) -- Tokyo stocks advanced Thursday morning with the benchmark Nikkei stock index rising to a two-year high.


The market was in a risk-on mood from the get go following the U.S. dollar's surge against the yen after the conclusion of the U.S. Federal Reserve's latest policy meeting.


The 225-issue Nikkei Stock Average gained 169.42 points Homme Nike Air Max 97 OG GS Chaussures Rouge , or 0.83 percent, from Wednesday to 20,479.88.


The broader Topix index of all First Section issues on the Tokyo Stock Exchange, meanwhile Air Max 97 OG GS Homme Nike Chaussures Bleu Pas Cher , added 11.85 points, or 0.71 percent, to 1,679.77.


A weak yen attracts buying Homme Nike Air Max 97 KPU TPU Chaussures Bleu Rouge , particularly of exporter issues whose firms' whose competitiveness increases in overseas markets and profits are augmented on favorable currency exchange rates when yields from overseas are repatriated.


Insurance, transportation equipment and mining-oriented stocks comprised those that advanced the most by the close of play.


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Rescue teams work to find survivors as Mexico quake toll reaches 230


In pics: general debate of UN General Assembly on day 2


Highlights of 10th China Acrobatics Golden Chrysanthemum Awards


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Wildlife paradise: Changtang National Nature Reserve in China's Tibet


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HANOI, March 1 (Xinhua) -- Vietnam's General Statistics Office (GSO) on Wednesday kicked off a nationwide economic survey to evaluate the performance of economic and administrative units from local to cent.

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