Predictive algorithms are used to identify areas likely to be affected by off-target DNA mutations, and refinements to the technology suggested that in those trials off-target effects would be few.
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Headley slid in as Buxton's throw was slightly off target.
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Westbrook took a long 24-point attempt that was off target.
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But, it also still had a number of off-target insertions.
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Despite employers' pleas, the new law may ultimately be off-target.
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Off-target mutations are definitely something researchers need to pay attention to.
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Your withering comments about the quality of German beers were off target.
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The stimulation can also impact undesired regions, potentially resulting in off-target effects.
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Otherwise, it will either be thrown way off target or burn up entirely.
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Of their other 10 shots, six were off target and four were blocked.
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It was off target, and the soldiers regarded the dirt plumes with indifference.
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Different guides can have different off-target effects depending on how they are used.
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Again and again she pitches off-target and again and again he strikes out.
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Pele. A lot of nice build-up for Croatia yields an off-target shot.
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Argentina takes it quick, but then wastes the chance with an off-target shot.
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ABE also seems to make fewer off-target edits: In one test, it mistakenly hit four of the 12 off-target sites, compared to CRISPR's nine, and made that mistake in 1.3 percent of cases compared to 14 percent for CRISPR, Liu said.
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Others are already dying around the world thanks to inaction and far off target setting.
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Another posited that it was a good reminder to hunt thoroughly for off-target effects.
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The tiniest mistake in his measurements could send the round hundreds of yards off target.
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Pedroia made a sliding stop but fired an off-target throw to Ramirez at first.
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If you have all three of those, your off-target rates can be extremely low.
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A pass wide, a cross in, a ball cleared, or blocked, or sent off target.
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The consequences of those off-target effects, far more extensive than previously realized, are largely unknown.
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And there are still many unknowns surrounding the safety of CRISPR and potential off-target effects.
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Hamilton scored when a throw to home from catcher David Ross to Lackey was off target.
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"If you think I wanted any sort of love relationship you're way off target," he wrote.
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So far, the synthetic chromosomes are not entirely without error—there were a few off-target effects.
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It also provides general feedback on how likely off-target effects are for the gene being targeted.
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Wall missed a jumper with 73 left and Beal's desperation fadeaway was off target to force overtime.
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Throwing even the most routine pass off target can have an avalanche effect on everything that follows.
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He said he would continue to do blood tests and analyze for mosaicism or off-target mutations.
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The roll-off target will be small and increase quarterly until it reaches $50 billion a month.
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Dicamba evaporates easily and travels to off-target plants but makers of newer versions, including DowDuPont DWDP.
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These off-target cuts can be dangerous, and scientists have been trying to find ways to prevent them.
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But the EU program to relocate asylum seekers from Italy to other EU countries remains far off target.
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Lionel Messi and Luis Suárez were both off-target with a handful of chances to seal the victory.
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Walkup then missed an off-balance shot with 23 seconds left, and Ty Charles's tip was off-target.
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Dr. He said he worked to minimize off-target effects and ultimately did not detect any after birth.
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But for an explosion that shattered windows within a mile, a few steps off target made little difference.
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It was Williams whose strokes were off target: Her 34 unforced errors were twice as many as Kenin's total.
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Those unintended changes to DNA, they found, were not detectable using common methods for checking for off-target effects.
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Bennett (below) is ostensibly the director of the absurdly, jaw-droppingly off-target ad that came late last week.
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Namely, the CRISPR-treated mice had around 1400 small off-target mutations and over 100 more considerable genetic alterations.
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|
According to the paper, the researchers didn't observe any physical effects of the off-target mutations at the time.
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|
Cousins' 3-pointer as time expired in regulation was off target, forcing overtime with the game tied at 104.
|
|
And most were either off target or so tame they were mere catching practice for Roma keeper Wojciech Szczesny.
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|
"Which of these off-target, beneficial effects should we pour our research dollars and effort into pursuing?" he asked.
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|
Daniel scored in the opening round of the shootout, but Henrik's attempt in the second round was off target.
|
|
He said the data he found persuaded him that the potential off-target effects of CRISPR had been over-hyped.
|
|
There's some evidence that CRISPR might make some unintended changes to other parts of the genome, called off-target effects.
|
|
Carta-Samuels drove Colorado State to the Colorado 222-yard line where Braxton Davis' field-goal attempt was off target.
|
|
When the holdings drift off target, it does make sense at some point to rebalance to restore the desired mix.
|
|
For the record, Belgium has five shots: De Bruyne's went in, two were off target and two were blocked. Wow.
|
|
Goalkeeper Hugo Lloris blocked a low shot from Diego Costa, and a low header by Eden Hazard was off target.
|
|
Josh Reddick followed with a single to left field, and Coghlan beat out an off-target throw home by Hicks.
|
|
Not expecting the help, Harden changed his mind in mid air, and flipped a pass off target towards the corner.
|
|
Given this disappointing performance, sheepish prognosticators have wondered whether any alternate source of information might have offset the off-target polling.
|
|
These off-target cuts can be dangerous, and scientists want to make sure there are as few of them as possible.
|
|
Importantly, in their paper the scientists reported finding no off-target effects, a major concern associated with using CRISPR in humans.
|
|
According to Brian Hilliard, U.K. economist at Société Générale, the BOE was early in its predictions rather than widely off-target.
|
|
Kershaw took off for third, and the throw from center was just barely off target, allowing Kershaw to slide in safely.
|
|
In July, Arkansas temporarily banned the use and sale of dicamba herbicides after farmers said the chemical was drifting off target.
|
|
The Bulls missed a chance to win when Dunn was off target on a mid-range jumper with 1.4 seconds left.
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|
As in, you can pick cells and there's absolutely no off-target effects and it can become a very precise tool.
|
|
Philip Krim&aposs price tag for his online mattress seller may have put off Target, Tempur Sealy, and Serta Simmons.5.
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|
The Blue Devils had a chance to win it, but Bagley settled for a long range three that was off target.
|
|
While Crispr is generally precise, it can have "off-target" effects, cutting DNA at places where it is not meant to.
|
|
But the rapid pace of advancement suggests the risks of off-target effects in CRISPR as not as high as once thought.
|
|
He wasn't intercepted Thursday night, but he was off-target for much of the game, going 23 of 264 for 248 yards.
|
|
One of the things standing in the way of turning that fantasy into reality, though, is the problem of off-target effects.
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|
Off-target effects are a problem—one that stands in the way of it being used as a tool in human therapies.
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A broken-bat single by Yadier Molina scored Matt Carpenter when left fielder Adam Duvall's throw to the plate was off target.
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|
She says off-target effects are a known issue with CRISPR but that this study isn't the best representation of those problems.
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|
We're definitely going to need more research to really figure out the extent of off-target mutations, when they happen, and why.
|
|
Mr Duncan Smith's motives may be dubious and his complaint off-target (the proposed disability cuts were less egregious than some others).
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|
But on a day when gusts sent arrows sailing far off target, she kept her head and her mistakes to a minimum.
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|
Theodore Roosevelt Jr.'s decision on Utah beach to fight from where his troops had landed, even though they landed off-target.
|
|
Although Harris is spot-on in her assertion that child care costs are a relevant issue, her proposed solution is off target.
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|
"If you were suggesting that somehow this is a genesis of a mistrial, I am saying that you're off target," he said.
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|
When Wawrinka blazed a forehand well off-target on Murray's first match point, the formerly top-ranked Murray celebrated a remarkable comeback.
|
|
The scientists then ran several experiments on human blood cells, to understand how to use the protein to prevent unintended, off-target cuts.
|
|
Now, several more studies have bolstered confidence in CRISPR, shedding light on how to potentially limit any off-target effects that do occur.
|
|
That same study that used a promiscuous CRISPR found that when CRISPR was more appropriately designed, there were no detectable off-target effects.
|
|
It's long been known that, even as precise a gene-editor as CRISPR is, off-target effects are a troublesome potential side effect.
|
|
While the scientific establishment is still embroiled in a debate over just how serious the problem is, CRISPR sometimes causes off-target effects.
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|
Two-thirds of the time, the NHC's 5-day forecast for a hurricane's track is 198 nautical miles, or 227 miles, off target.
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|
CRISPR seems to have cut only the DNA spots it was supposed to, without making any so-called off-target edits, he says.
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|
England continues to tempt fate in the back, with passes that arrive jusssst a bit late, or go jussssst a bit off target.
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|
This strategy led to highly precise and accurate editing, as evidenced by the lack of unintended off-target mutations in the embryos' genomes.
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|
Carrasco was covering first base in the fourth when he was injured following an awkward dive for an off-target throw from Carlos Santana.
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|
Chicago shortstop Addison Russell was off target on a throw to an outstretched first baseman Rizzo to get Votto on a game-ending groundout.
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|
Off-target mutations in other genes—a problem known with CRISPR—are still possible, the effects of which may reveal themselves a later time.
|
|
"Nanotechnology is one tool that we're trying to harness to maximize the benefit of a drug while minimizing the off-target effects," she says.
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|
But in recent years, experiments have found "off-target" effects from the technology — where genes besides the intended ones are altered — in human cells.
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|
On Wednesday, the rapper threw the ceremonial first pitch at the San Diego Padres game against the Atlanta Braves but was comically off target.
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|
The word means "off-target," or "amiss," but to Owen it represents the fact that his relationships, both old and new, have been false.
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|
Genome-editing techniques still aren't perfect, and they can sometimes misfire, leading to random mutations or other "off-target" effects in the edited cells.
|
|
In 2013, the Oreo flavor was so welcomed that packages flew off Target shelves and were being sold on eBay for $12 a box.
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|
There is lots of debate over how problematic the off-target effects of CRISPR really are, as well as over how to fix them.
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|
Unfortunately, since they are very powerful, when the mobile operator fires the weapon, the recoil will bring the rifle's barrel up and off target.
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|
Senegal has tried to launch a couple early attacks with long balls down the wings, but they've been way off target with their delivery.
|
|
Guillermo Heredia scored as left fielder Gerardo Parra struggled to grip the ball due to the wet conditions, and his throw was off target.
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|
"DARPA is extraordinarily sensitive to environmental risks and off-target effects, and has structured the Insect Allies program to identify and mitigate them," he said.
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|
Which is to say, they have "off-target effects," changing a gene you don't want changed or failing to change a gene that you do.
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There were no specific off-target mutations seen with the dogs, but it's a risk other future studies will have to continue watching out for.
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A first version of REPAIR caused nearly 20,000 off-target cuts, says study co-author Omar Abudayyeh, also a PhD student in the Zhang Lab.
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|
A key concern with CRISPR-edited cells is that the technique has been shown to create some "off-target" or unintended edits in the genome.
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|
One concern, for example, is that editing can alter DNA in places it isn't supposed to and that these "off-target" effects could trigger cancers.
|
|
Elevation will suggest which guide is least likely to result in off-target effects for a particular gene, using machine learning to figure it out.
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"There is also considerable concern about off-target effects, such as making mutations at sites in the genome other than the intended target," Carroll said.
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|
US crews blamed poor visibility in bad weather and said the strong winds of the jet stream often pushed bombs off target as they fell.
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|
Center Spencer Long reinjured a finger and had a half-dozen off-target shotgun hikes, including one on Baker's interception, which compounded problems for Darnold.
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We understand criticizing a famous artist is a good way to draw attention to those goals—and in this case, it is unjust and off-target.
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We understand criticizing a famous artist is a good way to draw attention to those goals---and in this case, it is unjust and off-target.
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If the most commonly used computer model is off target during high-impact weather events, it can affect the larger economy and possibly even cost lives.
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|
With five days to go till the closing ceremony, however, that goal seemed way off target as all those tipped for success had departed empty handed.
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Maybe even more impressively, researchers saw no evidence of "off-target effects" (in other words, CRISPR didn't edit the genes it was supposed to leave alone).
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He completed 03 of 16 passes for 127 yards and a touchdown and added a 35-yard scoring run, but was off target on several throws.
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|
Maryland's interim coach, Matt Canada, decided to try to end it right there, going for 27, but Tyrrell Pigrome's pass to Jeshaun Jones was off target.
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Dicamba herbicide has been blamed for moving off target and damaging crops that are unable to tolerate it, prompting calls for tighter restrictions on its use.
|
|
Although the girls were engineered to be resistant to HIV, many scientists are worried that "off-target" effects of the gene-editing could lead to other harms.
|
|
Study co-author Dr. Carl June, an immunologist at the University of Pennsylvania who pioneered CAR-T cell therapy, said the team found two off-target effects.
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This was found to produce the desired edit up to 60% of the time, but had fewer off-target insertions than the CAST system did, Sternberg adds.
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That educated guess is going to be right on the money for some people but significantly off target for others because, well, we are all very different.
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John Jaso led off the inning with a triple high off the right-field wall and continued home on second baseman Kolten Wong's off-target relay throw.
|
|
But the scientists were curious about what are known as "off-target" effects, or secondary mutations caused by CRISPR that occur away from the intended genetic target.
|
|
While some experts decried the paper as unnewsworthy (everyone's known about Crispr off-target mutations forever!) the majority of threads ticked off the experiment's flaws: Tiny sample size!
|
|
But, as the editorial points out, there is still little known about the off-target effects of CRISPR when used inside the body of a human or animal.
|
|
The fourth seed was tested early on his serve, which was initially off-target, but was able to maintain control of the contest with a strong returning display.
|
|
Researchers are developing a CRISPR "off-switch," a protein they can inject into affected cells that, when deployed, would make CRISPR stop cutting to reduce off-target effects.
|
|
But the rebalancing itself should be done only when one or more asset classes gets off target by a predetermined amount, such as 5 or 10 percentage points.
|
|
Los Angeles tied the game 2-2 in the fifth inning when Alex Verdugo scored on Max Muncy's grounder to first base, with Hosmer's throw home off-target.
|
|
Gene editing itself is experimental and is still associated with off-target mutations, capable of causing genetic problems early and later in life, including the development of cancer.
|
|
Muted and off target as she lost the first set to the 22011th-seeded Barty on Thursday night, Williams did not start the next set any more convincingly.
|
|
He was looking for Marshawn Lynch, but it was off target and Kuechly returned it 14 yards for the touchdown and a blazing fast 14-0 lead. [FOX]
|
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And even if these off-target mutations aren't harmful, research has shown that a mutation in the CCR5 gene can make people more susceptible to dying from the flu.
|
|
Like the previous Chinese study, this research shows how far we still are from being able to use CRISPR in a precise way, without triggering these "off target" mutations.
|
|
Despite that lopsided total, Philadelphia had arguably the best chances of the period on off-target shots, including Wayne Simmonds' shot off the post two minutes into the game.
|
|
Vanguard found that investors who wait to rebalance until their portfolios were 10 percentage points off target produced better long-term results than shifting the investment mix more often.
|
|
The Koreans were disappointed to grab only three golds in London, where their men missed out on the team title, but none were off target at the Rio Games.
|
|
The Privateers had a chance for a final shot, but Erik Thomas's inbounds pass with 26 seconds left was off target and was stolen by the Mountaineers' Chris Wray.
|
|
By the numbers: Testing on human and mouse cells in a lab, the researchers found prime editing, compared with other CRISPR techniques, showed low off-target edits at below 10%.
|
|
"It is more probable that this compound interacts with another, as yet unknown protein that is responsible for the observed toxicity," he suggested, a problem known as "off-target" interaction.
|
|
"The accuracy of the CRISPR gene editing technology and the off-target effects it brings are very controversial," more than 100 Chinese scientists said in their statement denouncing the experiments.
|
|
Also in contrast to the experiments in China, those led by Mitalipov reportedly produced very few "off-target" effects, or editing of genes that CRISPR was supposed to leave alone.
|
|
The off-target effects of CRISPR have long been known, but this new research highlights just how extensive they can be, and highlights the importance of research to understand them.
|
|
In general, it's safest to take a cell out of a patient and edit it (known as "ex vivo" treatment), because researchers can more easily check for off-target effects.
|
|
My heart rate reading was sometimes off target (compared to a Polar chest strap) by up to 30 beats per minute, no matter where or how I wore the Blaze.
|
|
The partnership aims to design new compounds that will "minimize unwanted off-target effects" of psychedelic-based drugs and make them as targeted and effective as possible for clinical trials.
|
|
There are serious concerns about using CRISPR to edit genes in adults with inheritable diseases, including off-target editing that can cause cancers and or large deletions and rearrangement of DNA.
|
|
Off-target effects could occur though, if the same letter occurs twice in the same snippet of code on which CRISPR is trained, also changing another C to a T accidentally.
|
|
A Massachusetts General Hospital team is looking at better ways to measure the on-target and off-target effects of gene editing, with a focus also on a mosquito gene drive.
|
|
"I just misread a number of putts today just by half a cup," said Spieth, who was off target on the lengthy putts he had made in the first three rounds.
|
|
However, a study just published in Nature Biotechnology has found that when CRISPR-Cas9 is used to edit genomes, off-target DNA damage is more common than had previously been appreciated.
|
|
In the new study researchers found that while those same algorithms successfully identified off-target effects of CRISPR in a petri dish, that didn't translate to work in the mice themselves.
|
|
"However, uncertainty about the effects of human cells on off-target organs and tissues in the chimeric animals, particularly in the nervous system, raises ethical and animal welfare concerns," she added.
|
|
Despite the dominance of possession, however, clear chances were few and far between, with Hugo Lloris saving comfortably from Emre Can and Thomas Mueller and Schweinsteiger off target when well-placed.
|
|
A risk with using CRISPR is that it could introduce some unintended changes, but no off-target mutations were detected in the gene-edited cells, the researchers reported in their study.
|
|
OFF-TARGET Seeking to reverse a downturn in oil prices that began in 2014, OPEC, Russia and other allies decided in late 2016 to reduce supply by some 1.8 million bpd.
|
|
You simply ask the Pruitt-led pro-industry EPA to ignore the legally required biological evaluations that revealed the widespread off-target killing tendencies of one of your most popular products.
|
|
The label instructions are also of interest to lawyers for farmers suing Monsanto, BASF and DuPont over damage they attribute to the potent weed killer moving off-target to nearby plants.
|
|
OFF-TARGET Seeking to reverse a downturn in oil prices that began in 2014, OPEC, Russia and other allies decided in late 2016 to reduce supply by some 1.8 million bpd.
|
|
Or it could be that the off-target cutting just happens more slowly, says study co-author Jacob Corn, an assistant adjunct professor of biochemistry, biophysics, and structural biology at UC Berkeley.
|
|
"Gene editing itself is experimental and is still associated with off-target mutations, capable of causing genetic problems early and later in life, including the development of cancer," Savulescu told the BBC.
|
|
A more recent study in mice found off-target mutations, particularly in the liver, with "very high frequencies" from inappropriately designed CRISPR interventions, but few if any problems in properly designed experiments.
|
|
But then, the team tweaked the system in a way that reduced the number of off-target cuts to 10 to 20 per target site, making it much more precise — and safe.
|
|
Still, Burgio says that the sequencing methods they used to check for off-target effects weren't enough, and it's possible the babies both have CRISPR-caused mutations that could harm their health.
|
|
But the researchers found that when they had used CRISPR to cure blindness in mice, it had resulted in not just a few but more than a thousand, unintended off-target effects.
|
|
Working with computer scientists and biologists from research institutions across the U.S., the company has developed a new tool called Elevation that predicts off-target effects when editing genes with the CRISPR.
|
|
The UN attempted an airdrop there last week but high winds meant all 21 tons of food went off target or missing, or their parachutes failed to open and they were destroyed.
|
|
"I look forward to continuing this dialogue to ensure US livestock remain well-protected from dangerous predators while simultaneously minimizing off-target impacts on both humans and non-predatory animals," Wheeler said.
|
|
The media company that engages in cargo-culting — hoping that by adopting the forms of the platform without its substance that it can succeed — will find itself outcompeted, overextended and off target.
|
|
Balancing the off-target effects of the therapy has also helped patients stay on the treatment, said Haviland, adding that the company has seen patients continue the therapy for nearly four years.
|
|
He said they found one embryo had a potential off-target (but the location was far from relevant genes) and one mosaic embryo, where only one of the two DNA strands was altered.
|
|
While CRISPR is heralded as a precision technique that makes editing genes as simple as cutting and pasting, it is not quite as precise as headlines suggest, and off-target effects do happen.
|
|
Off-target shooting, though, hasbeen an issue for Kansas State, which ranks eighth in the conference with a219 field-goal percentage, including a Big 23-worst 221 percent accuracy ratefrom 210-point range.
|
|
In 2015, Chinese researchers from Sun Yat-sen University in Guangzhou reported that only a fraction of dozens of human embryos that had been gene-edited with CRISPR lacked off-target gene alterations.
|
|
Of course, this might be a mix of wishful thinking and off-target speculation, and Waiti is there in his role as director with a microphone in front of him purely by chance.
|
|
This indicates the reproducibility of the science [...] However, this group of researchers also reproduced another finding described by the first group, namely that this type of gene editing also causes off-target effects.
|
|
After using their last timeout with 15 seconds left, the Blue Demons missed a chance to tie when Max Strus was off target on an off-balance 3-pointer with eight seconds left.
|
|
But the CRISPR technique isn't perfect, and in every few hundred cases, in what is referred to as "off-target events," it can edit the wrong portion of DNA, potentially creating unwanted mutations.
|
|
His timing was off, the usual sweet sound of ball-on-racket that is almost unique to the great Swiss was absent, replaced by a duller thud as shots repeatedly flew off target.
|
|
When the cell's natural repair process takes over, it can cause damage or, in the case where the modified DNA is inserted at the cut site, it can create unwanted off-target mutations.
|
|
The U.N. attempted an air drop there last week but high winds meant all 21 tonnes of food went off target or went missing or their parachutes failed to open and they were destroyed.
|
|
Hughes corralled a slightly off-target cross-ice pass from former league MVP Taylor Hall and then scored with a wrist shot from the right circle as the puck sailed over Raanta's left shoulder.
|
|
Target has jumped into the fray as well: On July 17, it will offer 30% off Target home brands, 25% off beauty and personal care products, and up to 30% off top Google products.
|
|
Kopitar took a shot from the right point that was off target, but the puck hit Toronto defenseman Nikita Zaitsev in the visor and ricocheted into the net, cutting the deficit to 20-28.
|
|
The ruling Law and Justice (PiS) party has supported the coal industry and in 2016 launched legislation which significantly slowed down investment in onshore wind, putting Warsaw off target for meeting the EU goals.
|
|
Chances throughout the game were thin on the ground, with Colombia striker Radamel Falcao heading off target in the 25th minute and again in the second half, while substitute Luis Muriel had an effort blocked.
|
|
Each forecasting group, including the National Oceanic and Atmospheric Administration (NOAA), which produces the official outlook for the U.S., has their own biases that can determine whether their projection proves prescient or wildly off target.
|
|
Memphis initially took control of the contest in the third quarter as Morant made a heads-up play on an off-target alley-oop attempt by finding a cutting Jaren Jackson Jr. for the conversion.
|
|
And, besides off-target editing or large deletions, another issue to worry about is mosaicism, where there could be a mix of edited and unedited genes that allow the targeted disease or health problem to continue.
|
|
This chart shows exactly how big the gap is: (A GtCO22020e is a gigaton of carbon dioxide equivalent — other greenhouse gases are effectively translated into CO22018.) So we're somewhere between 21.5 and 19 GtCO2e off-target.
|
|
OFF-TARGET ING's "Japanification" model — which takes into account factors such as growth, inflation, interest rates and demographics — suggests that over the last couple of years, the euro zone economy has shown symptoms of this malaise.
|
|
Lulu and Nana, the newly announced Chinese twin girls whose genes were edited to thwart HIV, face unknown and possibly dangerous health effects from unintended, or "off-target," damage to their DNA, experts told BuzzFeed News.
|
|
The firm's market capitalization was so off target that even Biscardi — who owns more than 103 percent of the stock — was unaware of the listed market capitalization of the company when CNBC called him this week.
|
|
OFF-TARGET ING's "Japanification" model -- which takes into account factors such as growth, inflation, interest rates and demographics -- suggests that over the last couple of years, the euro zone economy has shown symptoms of this malaise.
|
|
Perhaps this is why her summing up of the issues that concern parents — "whether their emphasis on independence and on allowing children flexibility to choose their own future is the right course" — feels so off target.
|
|
This show anchors the New Museum's third season in recent years devoted to women, and "Antibodies" will surely color your views of two concurrent exhibitions, one very strong and one off-target, by younger female artists.
|
|
Gonzalez lined out softly to second baseman Peraza, who threw to first trying to double up Stallings, but the ball was slightly off target, and the error allowed Kramer to score for a 4-4 tie.
|
|
Older versions of dicamba are known to easily evaporate and travel to off-target plants but makers of next-generation dicamba, also including DowDuPont, say the new products address the issue - provided farmers adhere to label instructions.
|
|
Tobias Harris hit three free throws in the final 8.2 seconds, and the Hornets missed a chance to tie the game when Jeremy Lamb was off target on a drive in the lane with two seconds remaining.
|
|
According to Deng, this was a success: the scientists didn't detect any gene editing-related adverse events, even if "more long-term in-depth studies are needed for off-target effects and other safety assessments," Deng said.
|
|
They zeroed in on issues that have shown up in previous studies: "off-target effects," or undesirable mutations in genome regions close to the targeted sequence, and mosaicism, where not all embryo cells make the desired changes.
|
|
He concluded, as a result of all this, that there might be one potential off-target mutation, that no mutation existed in the 609 cancer-associated genes he tested and that no large chunks of DNA were missing.
|
|
While he does not offer advice to underground chemists, he checked into it later and found that it has "off-target" effects, which means that it might potentially cause similar problems to those seen in the clinical trial.
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Currently, if you wanted to edit an embryo, you'd have to do it once the sperm and egg had already fused, and then hope you got a couple embryos with the desired traits and no off-target effects.
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This approach minimizes potential mistakes, known as off-target effects, because Crispr is only in the cells for a short period of time, meaning they aren't as likely to go rogue and break DNA they're not supposed to.
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"With [CRISPR/Cas2500] gene editing, we know we can make the desired change, but sometimes we also make off-target or unintended changes in the genome," said the Broad Institute's Feng Zhang, a senior author on the paper.
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A fix for the thrusters was flight-tested in 2016 — and it was described as a success until an LA Times investigation revealed that, in fact, one of the thrusters had failed and thrown the interceptor way off target.
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"With significant adoption and a lot of interest in this new technology, we recognize that many states have received a number of reports of potential off-target application of dicamba in 2017," Monsanto spokeswoman Charla Lord said last month.
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In order for an ICBM to deliver its payload to a target, it must survive the intense heat of re-entering the earth's atmosphere after a brief space flight, not breaking up or going off target in the process.
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Kolten Wong bunted toward third base, and Marlins catcher Jorge Alfaro pounced on the ball, but his off-target throw sailed off the glove of first baseman Garrett Cooper for an error that allowed Goldschmidt and Ozuna to score.
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And, though the off-target mutations and accidental deletion of sections of DNA that CRISPR can cause may not matter too much if (as is often the case) crops are the recipients, they matter a lot if the recipient is human.
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The Chinese experiments using CRISPR caused errors when genes were edited, a phenomenon scientists call mosaicism; only some of the cells in an embryo were receptive to the editing, while others didn't repair as desired and exhibited "off-target" effects.
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The company plans to present data at the summit that it says show user error was behind the damage, contrary to academics' findings that dicamba products can vaporize and move off target under certain conditions in a process known as volatilization.
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The project was largely carried out in secret, the medical necessity for inactivation of CCR5 in these infants is utterly unconvincing, the informed consent process appears highly questionable, and the possibility of damaging off-target effects has not been satisfactorily explored.
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Brett Phillips tracked it down and fired a throw to shortstop Orlando Arcia, whose relay was slightly off-target, but Vogt reached out, grabbed it and managed to hold onto the ball and tag Duvall as he tried to come home.
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Most earlier efforts to edit embryos in a laboratory dish have resulted in some unintended effects, like off-target mutations that can occur in other genes, or mosaicism, in which the altered gene appears in some cells but not others.
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Virtually all of these cannabinoids bind to the CB1 receptor in the brain, but beyond that there are enormous variations in potency, functional activity, off-target binding, and an enormously diverse population of users taking different doses often in combination with other drugs.
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Chinese scientists conducted a similar experiment using CRISPR on embryos in 2015, but those embryos reportedly resulted in something called "mosaicism," which are off-target genetic mutations that happen when the changes to DNA are adopted by only some of the cells.
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A claim in a paper last year that CRISPR caused many off-target side-effects was retracted over interpretations of data, and a report that that humans may be immune to Cas9 was determined to be something that could be worked around.
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Tom Price, the secretary of health and human services, has also laced into its work recently, pointing to its off-target estimates of the Affordable Care Act as evidence that it is ill equipped to pass judgment over the new Republican health plan.
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A series of off-target costumes (by Ramona Ponce) contributes to the inadvertent sense of artifice, especially when Amy arrives at her art opening looking like a rube in a red beret that Mark or Claire surely should tell her to remove immediately.
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The possibility of unintended effects is still a concern in developing any CRISPR therapy—another study published online last week as a preprint showed that when using a "deliberately promiscuous" form of CRISPR in a mouse liver, there were hundreds of off-target gene edits.
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What's more, it's poised to increase the accuracy of human genome editing, which could make CRISPR more palatable for those worried about "off target" mutations; the system has been used on human embryos, but it produced far too many unintended mutations for scientists' liking.
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If scientists wanted to use CRISPR to cut one mutation out of a patient's DNA and replace it with functional DNA, there's no foolproof way to make sure that CRISPR made only the one cut instead of 10 unintended edits, called off-target effects.
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Moments later, France goalkeeper Hugo Lloris ensured his side went in at the break with the advantage, producing a brilliant one-handed save to keep out a Martin Caceres header although Diego Godin will be disappointed his follow-up shot was wildly off target.
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Fields struggled early to find rhythm in his passing game and was off-target on his first three throws but connected on a 57-yard touchdown pass to receiver Chris Olave to give the Buckeyes breathing room at the end of the first quarter.
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"The bottom line is that it threatens to increase exposure to toxic pesticide drift, reverting back to the pre-AEZ era where EPA and others recognized that off-target drift was a significant public health problem and that simply requiring no contact was not sufficient," Figueroa said.
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And in June, a pair of studies in the journal Nature Biotechnology jarred the gene-editing world by finding CRISPR off-target effects could damage a gene that protected people from cancer in both eye cells and the stem cells that the body uses to repair injuries.
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Korda spent an age lining up the putt as an anxious Jessica looked on from behind the green, but her effort soon drifted off target as she was left to be consoled by her sister and ponder what might have been after a torturous near-miss.
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KEY RATING DRIVERS The revision of the Outlook on Portugal's IDRs reflects the following key rating drivers and their relative weights: MEDIUM Fiscal performance was well off-target in 2015, with the general government deficit at an estimated 443% of GDP compared with the 2.7% initially expected.
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"Even with a viable piglet, we cannot be sure there were no off target effects until the pigs are extensively studied for physiological and behavior changes," William Muir, a professor of animal sciences at Purdue University, who wasn't involved in the research, writes in an email to The Verge.
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France forward Kylian Mbappe, who had ripped apart Argentina in the previous round with his directness and pace, wasted a good opportunity to open the scoring in the 15th minute when Olivier Giroud headed across the box to him but the 19-year-old's looping header was off-target.
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In a game characterized by walks, wild pitches, hit batters, errors, Alex Cora's ejection and an errant throw that was so far off target it hit an umpire in the shoulder, the Astros beat the sloppy Boston Red Sox, 7-2, to grab Game 1 of the best-of-seven series.
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"It's critically important to look closely at genomes being edited with the Crispr system, ideally with a method sensitive enough to detect even rare off-target events," says Stephen Floor, a biophysicist who worked in Crispr creator Jennifer Doudna's lab at UC Berkeley before beginning his own gene editing cancer research at UCSF.
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Why it matters: The technique, called prime editing, adds a third editing tool for mammalian cells in a manner that lessens the rate of the dangerous off-target deletions or insertions caused by the other types of tools, according to Broad Institute's David Liu, co-author of the paper published in Nature.
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That said, there are a few reasons to be optimistic that going small could pay off: Target began experimenting with small-formats in big cities and on college campuses, opening nine in 2014, and they have driven sales well enough that it is planning to open hundreds more in the coming years.
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Why it matters: While this research is still in early stages, as both teams tested their techniques on bacterial cells, experts say the technique could allow edited genes to be more precisely inserted into genomes, possibly addressing concerns with current CRISPR systems that can lead to off-target editing and random deletions or even cancer.
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"Since coming out of stealth mode last September, the CODA team has made tremendous progress in developing its gene therapy program that is tunable, durable and highly selective, which allows for better efficacy and safety with fewer off-target effects," said Tom Woiwode, PhD, managing director at Versant Ventures and Coda Chairman, in a statement.
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The exact genetic makeup of the lab mice's parents was not known, and the control group of mice and the CRISPR'd mice weren't siblings, the editorial explained, so it was impossible for the researchers to tell whether the genetic differences between the control mice and the CRISPR'd mice was due to off-target effects or just natural variation.
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Moreover, BEst's mid-2015 projections proved to be off target, only placing 10% of the Fitch China100 portfolio in negative zones characterised by rising leverage; in reality, 13% ended up in negative zones, including 11 companies in the "Red Pain Zone" of BEst-projected EBITDA decline and rising net debt, as EBITDA forecasts proved overly optimistic.
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By the formula V=GMr, where M is the mass of the Earth in kilograms, r is the orbital radius in meters, G is the constant for gravity, and V is the resulting velocity, the rocket thrusters gave the rocket the wrong velocity at the wrong radius, leading the rocket mass to be off target of the ISS.
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But the final nail in the CRISPR coffin seems to have come this week, when the original study authors posted a new preprint paper in which, in a new mouse experiment, they used their previous methodology to look for potential off-target effects and did not find an excess of unintended genetic mutations, as they had in their initial work.
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If Pearce had not anchored the toe of his right foot to first base, as he did, if the plastic cleats on the bottom of his shoe were a tiny bit shorter, or if the throw to him was slightly more off target, the Yankees might have won Game 228 and carried a plane-load of momentum into a do-or-die Game 24 at Fenway Park, potentially changing the course of the postseason.
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