Archive for the ‘Crispr’ Category
Gene-editing tool ‘CRISPR’ gaining massive attention – KMOV.com
Precision editing DNA allows for some amazing applications. Ian Haydon, CC BY-ND
Ian Haydon, University of Washington
Theres a revolution happening in biology, and its name is CRISPR.
CRISPR (pronounced crisper) is a powerful technique for editing DNA. It has received an enormous amount of attention in the scientific and popular press, largely based on the promise of what this powerful gene-editing technology will someday do.
CRISPR was Science magazines 2015 Breakthrough of the Year; its been featured prominently in the New Yorker more than once; and The Hollywood Reporter revealed that Jennifer Lopez will be the executive producer on an upcoming CRISPR-themed NBC bio-crime drama. Not bad for a molecular biology laboratory technique.
Two of the CRISPR co-inventors, Emmanuelle Charpentier (middle-left) and Jennifer Doudna (middle-right), rubbing elbows with celebs after receiving the 2015 Breakthrough Prize in Life Sciences. Breakthrough Prize Foundation, CC BY-ND
CRISPR is not the first molecular tool designed to edit DNA, but it gained its fame because it solves some longstanding problems in the field. First, it is highly specific. When properly set up, the molecular scissors that make up the CRISPR system will snip target DNA only where you want them to. It is also incredibly cheap. Unlike previous gene editing systems which could cost thousands of dollars, a relative novice can purchase a CRISPR toolkit for less than US$50.
Research labs around the world are in the process of turning the hype surrounding the CRISPR technique into real results. Addgene, a nonprofit supplier of scientific reagents, has shipped tens of thousands of CRISPR toolkits to researchers in more than 80 countries, and the scientific literature is now packed with thousands of CRISPR-related publications.
When you give scientists access to powerful tools, they can produce some pretty amazing results.
The most promising (and obvious) applications of gene editing are in medicine. As we learn more about the molecular underpinnings of various diseases, stunning progress has been made in correcting genetic diseases in the laboratory just over the past few years.
Take, for example, muscular dystrophy a complex and devastating family of diseases characterized by the breakdown of a molecular component of muscle called dystrophin. For some types of muscular dystrophy, the cause of the breakdown is understood at the DNA level.
In 2014, researchers at the University of Texas showed that CRISPR could correct mutations associated with muscular dystrophy in isolated fertilized mouse eggs which, after being reimplanted, then grew into healthy mice. By February of this year, a team here at the University of Washington published results of a CRISPR-based gene replacement therapy which largely repaired the effects of Duchenne muscular dystrophy in adult mice. These mice showed significantly improved muscle strength approaching normal levels four months after receiving treatment.
Using CRISPR to correct disease-causing genetic mutations is certainly not a panacea. For starters, many diseases have causes outside the letters of our DNA. And even for diseases that are genetically encoded, making sense of the six billion DNA letters that comprise the human genome is no small task. But here CRISPR is again advancing science; by adding or removing new mutations or even turning whole genes on or off scientists are beginning to probe the basic code of life like never before.
CRISPR is already showing health applications beyond editing the DNA in our cells. A large team out of Harvard and MIT just debuted a CRISPR-based technology that enables precise detection of pathogens like Zika and dengue virus at extremely low cost an estimated $0.61 per sample.
Using their system, the molecular components of CRISPR are dried up and smeared onto a strip of paper. Samples of bodily fluid (blood serum, urine or saliva) can be applied to these strips in the field and, because they linked CRISPR components to fluorescent particles, the amount of a specific virus in the sample can be quantified based on a visual readout. A sample that glows bright green could indicate a life-threatening dengue virus infection, for instance. The technology can also distinguish between bacterial species (useful for diagnosing infection) and could even determine mutations specific to an individual patients cancer (useful for personalized medicine).
Feng Zhang, another co-inventor of CRISPR technology, discussing its safety and ethical ramifications. AP Photo/Susan Walsh
Almost all of CRISPRs advances in improving human health remain in an early, experimental phase. We may not have to wait long to see this technology make its way into actual, living people though; the CEO of the biotech company Editas has announced plans to file paperwork with the Food and Drug Administration for an investigational new drug (a necessary legal step before beginning clinical trials) later this year. The company intends to use CRISPR to correct mutations in a gene associated with the most common cause of inherited childhood blindness.
Physicians and medical researchers are not the only ones interested in making precise changes to DNA. In 2013, agricultural biotechnologists demonstrated that genes in rice and other crops could be modified using CRISPR for instance, to silence a gene associated with susceptibility to bacterial blight. Less than a year later, a different group showed that CRISPR also worked in pigs. In this case, researchers sought to modify a gene related to blood coagulation, as leftover blood can promote bacterial growth in meat.
You wont find CRISPR-modified food in your local grocery store just yet. As with medical applications, agricultural gene editing breakthroughs achieved in the laboratory take time to mature into commercially viable products, which must then be determined to be safe. Here again, though, CRISPR is changing things.
A common perception of what it means to genetically modify a crop involves swapping genes from one organism to another putting a fish gene into a tomato, for example. While this type of genetic modification known as transfection has actually been used, there are other ways to change DNA. CRISPR has the advantage of being much more programmable than previous gene editing technologies, meaning very specific changes can be made in just a few DNA letters.
This precision led Yinong Yang a plant biologist at Penn State to write a letter to the USDA in 2015 seeking clarification on a current research project. He was in the process of modifying an edible white mushroom so it would brown less on the shelf. This could be accomplished, he discovered, by turning down the volume of just one gene.
White Agaricus bisporus mushrooms with no browning are more visually appealing. Olha Afanasieva/Shutterstock.com
Yang was doing this work using CRISPR, and because his process did not introduce any foreign DNA into the mushrooms, he wanted to know if the product would be considered a regulated article by the Animal and Plant Health Inspection Service, a division of the U.S. Department of Agriculture tasked with regulating GMOs.
APHIS does not consider CRISPR/Cas9-edited white button mushrooms as described in your October 30, 2015 letter to be regulated, they replied.
Yangs mushrooms were not the first genetically modified crop deemed exempt from current USDA regulation, but they were the first made using CRISPR. The heightened attention that CRISPR has brought to the gene editing field is forcing policymakers in the U.S. and abroad to update some of their thinking around what it means to genetically modify food.
One particularly controversial application of this powerful gene editing technology is the possibility of driving certain species to extinction such as the most lethal animal on Earth, the malaria-causing Anopheles gambiae mosquito. This is, as far as scientists can tell, actually possible, and some serious players like the Bill and Melinda Gates Foundation are already investing in the project. (The BMGF funds The Conversation Africa.)
Most CRISPR applications are not nearly as ethically fraught. Here at the University of Washington, CRISPR is helping researchers understand how embryonic stem cells mature, how DNA can be spatially reorganized inside living cells and why some frogs can regrow their spinal cords (an ability we humans do not share).
It is safe to say CRISPR is more than just hype. Centuries ago we were writing on clay tablets in this century we will write the stuff of life.
Ian Haydon, Doctoral Student in Biochemistry, University of Washington
This article was originally published on The Conversation. Read the original article.
Here is the original post:
Gene-editing tool 'CRISPR' gaining massive attention - KMOV.com
Can CRISPR feed the world? – Phys.org – Phys.Org
May 18, 2017 by Gary Finnegan, From Horizon Researchers in Norwich, UK, are hoping to make crops more resistant to disease. Credit: Kamoun Lab @ TSL
As the world's population rises, scientists want to edit the genes of potatoes and wheat to help them fight plant diseases that cause famine.
By 2040, there will be 9 billion people in the world. "That's like adding another China onto today's global population," said Professor Sophien Kamoun of the Sainsbury Laboratory in Norwich, UK.
Prof. Kamoun is one of a growing number of food scientists trying to figure out how to feed the world. As an expert in plant pathogens such as Phytophthora infestans the fungus-like microbe responsible for potato blight he wants to make crops more resistant to disease.
Potato blight sparked the Irish famine in the 19th century, causing a million people to starve to death and another million migrants to flee. European farmers now keep the fungus in check by using pesticides. However, in regions without access to chemical sprays, it continues to wipe out enough potatoes to feed hundreds of millions of people every year.
"Potato blight is still a problem," said Prof. Kamoun. "In Europe, we use 12 chemical sprays per season to manage the pathogen that causes blight, but other parts of the world cannot afford this."
Plants try to fight off the pathogens that cause disease but these are continuously changing to evade detection by the plant's immune system.
Arms race
In nature, every time a plant gets a little better at fighting off infection, pathogens adapt to evade their defences. Now biologists are getting involved in the fight.
"It's essentially an arms race between plants and pathogens," said Prof. Kamoun. "We want to turn it into an arms race between biotechnologists and pathogens by generating new defences in the lab."
Five years ago, Prof. Kamoun embarked on a project called NGRB, funded by the EU's European Research Council. The plan was to find a way to make potatoes more resistant to infection using advanced plant-breeding techniques.
Then serendipity struck. In the early stages of the project, scientists in another lab discovered a ground-breaking gene-editing technique known as CRISPR-Cas which allows scientists to delete or add genes at will. As well as having potential medical applications in humans, this powerful tool is unlocking new approaches to perfecting plants.
"If we think of the genome as text, CRISPR is a word processor that allows us to change just a letter or two," explained Prof. Kamoun. "The precision that this allows makes CRISPR the ultimate in genetic editing. It's really beautiful."
One of the simplest ways to use CRISPR to improve plants is to remove a gene that makes them vulnerable to infection. This alone can make potatoes more resilient, helping to meet the world's growing demand for food.
The resulting crop looks and tastes just the same as any other potato. Prof. Kamoun says that potatoes which are missing a gene or two should not be viewed in the same way as genetically modified foods which sometimes contain genes introduced from another species. "It's a very important technical difference but not all regulators have updated their rules to make this distinction."
Potatoes are not the only food crops that can be improved by CRISPR-Cas. Prof. Kamoun is now working on a project that aims to protect wheat from wheat blast a fungal disease decimating yields in Bangladesh and spreading in Asia.
Looking ahead, CRISPR will be used to improve the quality and nutritional value of wheat, rice, potatoes and vegetables. It could even be used to remove genes that cause allergic reactions in people with tomato or wheat intolerance.
"If we can remove allergens, consumers may soon see hypoallergenic tomatoes on supermarket shelves," Prof. Kamoun said. "It's a very exciting technology."
While targeting disease in this way could be a game changer for global food security in the years ahead, experts believe other approaches to plant breeding will continue to have a role. Understanding meiosis a type of cell division that can reshuffle genes to improve plants can help farmers and the agribusiness sector select for hardier crops, according to Professor Chris Franklin of the University of Birmingham, UK.
He leads the COMREC project, which trains young scientists to understand and manipulate meiosis in plants. The project applies the wealth of knowledge generated by leaders in the field to tackle the pressing problem of feeding a hungry world.
"COMREC has begun to translate fundamental research into (applications in) key crop species such as cereals, brassicas and tomato," said Prof. Franklin. "Close links with plant-breeding companies have provided important insight into the specific challenges confronted by the breeders."
Elite crops
There may be untapped potential in this approach to plant breeding: most of the genes naturally reshuffled during meiosis in cereal crops are at the far ends of chromosomes genes in the middle of chromosomes are rarely reshuffled, limiting the scope for new crop variations.
COMREC's academic and industry partners hope to understand why this is so that they can find a way to shuffle the genes in the middle of chromosomes too. And the food industry is keen to produce new 'elite varieties' that are better adapted to confront the challenges arising from climate change, says Prof. Franklin.
"A number of genes have now been identified that can make this reshuffling relatively more frequent," he said. "CRISPR-Cas provides a way to modify the corresponding genes in crop species, helping to translate this basic research to target crops."
Explore further: US approves 3 types of genetically engineered potatoes (Update)
More information: Targeted mutagenesis in the model plant Nicotiana benthamiana using Cas9 RNA-guided endonuclease by Vladimir Nekrasov, Brian Staskawicz, Detlef Weigel, Jonathan D G Jones & Sophien Kamoun in Nature Biotechnology 31, 691693 (2013). DOI: 10.1038/nbt.2655
Involvement of the Cohesin Cofactor PDS5 (SPO76) During Meiosis and DNA Repair in Arabidopsis thaliana by Mnica Pradillo, Alexander Knoll, Cecilia Oliver, Javier Varas, Eduardo Corredor, Holger Puchta and Juan L. Santos in Front. Plant Sci., 01 December 2015 . DOI: 10.3389/fpls.2015.01034
Three types of potatoes genetically engineered to resist the pathogen that caused the Irish potato famine are safe for the environment and safe to eat, federal officials have announced.
Scientists on Monday said they have found a gene to help protect potatoes from a blight that unleashed a devastating famine in Ireland in the 19th century.
Growing crops with stacks of two or more resistance genes from closely related species, introduced into the crop via for instance genetic engineering, combined with the simultaneous introduction of resistance management, ...
A team of scientists from The Sainsbury Laboratory (TSL) and The Genome Analysis Centre (TGAC) have developed a new method to accelerate isolation of plant disease resistance genes. The team have also identified a brand new ...
When you pick up the perfect apple in the supermarket it's easy to forget that plants get sick just like we do. A more realistic view might come from a walk outside during summer: try to find a leaf without a speck, spot ...
We all know that animals have an immune system - but plants have systems to fight infection too. Plant cells have receptor proteins which bind with parts of a pathogen. These receptor proteins are located on the surface of ...
(Phys.org)A pair of researchers from Stanford University has studied the energy used by a type of small parrot as it hops from branch to branch during foraging. As they note in their paper uploaded to the open access site ...
A new Oxford University collaboration revealing the world's prime insect predation hotspots, achieved its landmark findings using an unusual aid: plasticine 'dummy caterpillars.'
Breeding in plants and animals typically involves straightforward addition. As beneficial new traits are discoveredlike resistance to drought or larger fruitsthey are added to existing prized varieties, delivered via ...
After decades of research aiming to understand how DNA is organized in human cells, scientists at the Gladstone Institutes have shed new light on this mysterious field by discovering how a key protein helps control gene organization.
Researchers have successfully developed a novel method that allows for increased disease resistance in rice without decreasing yield. A team at Duke University, working in collaboration with scientists at Huazhong Agricultural ...
University of Chicago psychology professor Leslie Kay and her research group set out to resolve a 15-year-old scientific dispute about how rats process odors. What they found not only settles that argument, it suggests an ...
Please sign in to add a comment. Registration is free, and takes less than a minute. Read more
Excerpt from:
Easy DNA Editing Will Remake the World. Buckle Up – WIRED
Im sorry; your browser does not support HTML5 video in WebM with VP8 or MP4 with H.264.
Spiny grass and scraggly pines creep amid the arts-and-crafts buildings of the Asilomar Conference Grounds, 100 acres of dune where California's Monterey Peninsula hammerheads into the Pacific. It's a rugged landscape, designed to inspire people to contemplate their evolving place on Earth. So it was natural that 140 scientists gathered here in 1975 for an unprecedented conference.
They were worried about what people called recombinant DNA, the manipulation of the source code of life. It had been just 22 years since James Watson, Francis Crick, and Rosalind Franklin described what DNA wasdeoxyribonucleic acid, four different structures called bases stuck to a backbone of sugar and phosphate, in sequences thousands of bases long. DNA is what genes are made of, and genes are the basis of heredity.
Preeminent genetic researchers like David Baltimore, then at MIT, went to Asilomar to grapple with the implications of being able to decrypt and reorder genes. It was a God-like powerto plug genes from one living thing into another. Used wisely, it had the potential to save millions of lives. But the scientists also knew their creations might slip out of their control. They wanted to consider what ought to be off-limits.
By 1975, other fields of sciencelike physicswere subject to broad restrictions. Hardly anyone was allowed to work on atomic bombs, say. But biology was different. Biologists still let the winding road of research guide their steps. On occasion, regulatory bodies had acted retrospectivelyafter Nuremberg, Tuskegee, and the human radiation experiments, external enforcement entities had told biologists they weren't allowed to do that bad thing again. Asilomar, though, was about establishing prospective guidelines, a remarkably open and forward-thinking move.
At the end of the meeting, Baltimore and four other molecular biologists stayed up all night writing a consensus statement. They laid out ways to isolate potentially dangerous experiments and determined that cloning or otherwise messing with dangerous pathogens should be off-limits. A few attendees fretted about the idea of modifications of the human germ linechanges that would be passed on from one generation to the nextbut most thought that was so far off as to be unrealistic. Engineering microbes was hard enough. The rules the Asilomar scientists hoped biology would follow didn't look much further ahead than ideas and proposals already on their desks.
Earlier this year, Baltimore joined 17 other researchers for another California conference, this one at the Carneros Inn in Napa Valley. It was a feeling of dj vu, Baltimore says. There he was again, gathered with some of the smartest scientists on earth to talk about the implications of genome engineering.
The stakes, however, have changed. Everyone at the Napa meeting had access to a gene-editing technique called Crispr-Cas9. The first term is an acronym for clustered regularly interspaced short palindromic repeats, a description of the genetic basis of the method; Cas9 is the name of a protein that makes it work. Technical details aside, Crispr-Cas9 makes it easy, cheap, and fast to move genes aroundany genes, in any living thing, from bacteria to people. These are monumental moments in the history of biomedical research, Baltimore says. They don't happen every day.
Using the three-year-old technique, researchers have already reversed mutations that cause blindness, stopped cancer cells from multiplying, and made cells impervious to the virus that causes AIDS. Agronomists have rendered wheat invulnerable to killer fungi like powdery mildew, hinting at engineered staple crops that can feed a population of 9 billion on an ever-warmer planet. Bioengineers have used Crispr to alter the DNA of yeast so that it consumes plant matter and excretes ethanol, promising an end to reliance on petrochemicals. Startups devoted to Crispr have launched. International pharmaceutical and agricultural companies have spun up Crispr R&D. Two of the most powerful universities in the US are engaged in a vicious war over the basic patent. Depending on what kind of person you are, Crispr makes you see a gleaming world of the future, a Nobel medallion, or dollar signs.
The technique is revolutionary, and like all revolutions, it's perilous. Crispr goes well beyond anything the Asilomar conference discussed. It could at last allow genetics researchers to conjure everything anyone has ever worried they woulddesigner babies, invasive mutants, species-specific bioweapons, and a dozen other apocalyptic sci-fi tropes. It brings with it all-new rules for the practice of research in the life sciences. But no one knows what the rules areor who will be the first to break them.
In a way, humans were genetic engineers long before anyone knew what a gene was. They could give living things new traitssweeter kernels of corn, flatter bulldog facesthrough selective breeding. But it took time, and it didn't always pan out. By the 1930s refining nature got faster. Scientists bombarded seeds and insect eggs with x-rays, causing mutations to scatter through genomes like shrapnel. If one of hundreds of irradiated plants or insects grew up with the traits scientists desired, they bred it and tossed the rest. That's where red grapefruits came from, and most barley for modern beer.
Genome modification has become less of a crapshoot. In 2002, molecular biologists learned to delete or replace specific genes using enzymes called zinc-finger nucleases; the next-generation technique used enzymes named TALENs.
Yet the procedures were expensive and complicated. They only worked on organisms whose molecular innards had been thoroughly dissectedlike mice or fruit flies. Genome engineers went on the hunt for something better.
Scientists have used it to render wheat invulnerable to killer fungi. Such crops could feed billions of people.
As it happened, the people who found it weren't genome engineers at all. They were basic researchers, trying to unravel the origin of life by sequencing the genomes of ancient bacteria and microbes called Archaea (as in archaic), descendants of the first life on Earth. Deep amid the bases, the As, Ts, Gs, and Cs that made up those DNA sequences, microbiologists noticed recurring segments that were the same back to front and front to backpalindromes. The researchers didn't know what these segments did, but they knew they were weird. In a branding exercise only scientists could love, they named these clusters of repeating palindromes Crispr.
Then, in 2005, a microbiologist named Rodolphe Barrangou, working at a Danish food company called Danisco, spotted some of those same palindromic repeats in Streptococcus thermophilus, the bacteria that the company uses to make yogurt and cheese. Barrangou and his colleagues discovered that the unidentified stretches of DNA between Crispr's palindromes matched sequences from viruses that had infected their S. thermophilus colonies. Like most living things, bacteria get attacked by virusesin this case they're called bacteriophages, or phages for short. Barrangou's team went on to show that the segments served an important role in the bacteria's defense against the phages, a sort of immunological memory. If a phage infected a microbe whose Crispr carried its fingerprint, the bacteria could recognize the phage and fight back. Barrangou and his colleagues realized they could save their company some money by selecting S. thermophilus species with Crispr sequences that resisted common dairy viruses.
As more researchers sequenced more bacteria, they found Crisprs again and againhalf of all bacteria had them. Most Archaea did too. And even stranger, some of Crispr's sequences didn't encode the eventual manufacture of a protein, as is typical of a gene, but instead led to RNAsingle-stranded genetic material. (DNA, of course, is double-stranded.)
That pointed to a new hypothesis. Most present-day animals and plants defend themselves against viruses with structures made out of RNA. So a few researchers started to wonder if Crispr was a primordial immune system. Among the people working on that idea was Jill Banfield, a geomicrobiologist at UC Berkeley, who had found Crispr sequences in microbes she collected from acidic, 110-degree water from the defunct Iron Mountain Mine in Shasta County, California. But to figure out if she was right, she needed help.
Luckily, one of the country's best-known RNA experts, a biochemist named Jennifer Doudna, worked on the other side of campus in an office with a view of the Bay and San Francisco's skyline. It certainly wasn't what Doudna had imagined for herself as a girl growing up on the Big Island of Hawaii. She simply liked math and chemistryan affinity that took her to Harvard and then to a postdoc at the University of Colorado. That's where she made her initial important discoveries, revealing the three-dimensional structure of complex RNA molecules that could, like enzymes, catalyze chemical reactions.
The mine bacteria piqued Doudna's curiosity, but when Doudna pried Crispr apart, she didn't see anything to suggest the bacterial immune system was related to the one plants and animals use. Still, she thought the system might be adapted for diagnostic tests.
Banfield wasn't the only person to ask Doudna for help with a Crispr project. In 2011, Doudna was at an American Society for Microbiology meeting in San Juan, Puerto Rico, when an intense, dark-haired French scientist asked her if she wouldn't mind stepping outside the conference hall for a chat. This was Emmanuelle Charpentier, a microbiologist at Umea University in Sweden.
As they wandered through the alleyways of old San Juan, Charpentier explained that one of Crispr's associated proteins, named Csn1, appeared to be extraordinary. It seemed to search for specific DNA sequences in viruses and cut them apart like a microscopic multitool. Charpentier asked Doudna to help her figure out how it worked. Somehow the way she said it, I literallyI can almost feel it nowI had this chill down my back, Doudna says. When she said the mysterious Csn1 I just had this feeling, there is going to be something good here.
Back in Sweden, Charpentier kept a colony of Streptococcus pyogenes in a biohazard chamber. Few people want S. pyogenes anywhere near them. It can cause strep throat and necrotizing fasciitisflesh-eating disease. But it was the bug Charpentier worked with, and it was in S. pyogenes that she had found that mysterious yet mighty protein, now renamed Cas9. Charpentier swabbed her colony, purified its DNA, and FedExed a sample to Doudna.
Working together, Charpentiers and Doudnas teams found that Crispr made two short strands of RNA and that Cas9 latched onto them. The sequence of the RNA strands corresponded to stretches of viral DNA and could home in on those segments like a genetic GPS. And when the Crispr-Cas9 complex arrives at its destination, Cas9 does something almost magical: It changes shape, grasping the DNA and slicing it with a precise molecular scalpel.
Jennifer Doudna did early work on Crispr. Photo by: Bryan Derballa
Heres whats important: Once theyd taken that mechanism apart, Doudnas postdoc, Martin Jinek, combined the two strands of RNA into one fragmentguide RNAthat Jinek could program. He could make guide RNA with whatever genetic letters he wanted; not just from viruses but from, as far as they could tell, anything. In test tubes, the combination of Jineks guide RNA and the Cas9 protein proved to be a programmable machine for DNA cutting. Compared to TALENs and zinc-finger nucleases, this was like trading in rusty scissors for a computer-controlled laser cutter. I remember running into a few of my colleagues at Berkeley and saying we have this fantastic result, and I think its going to be really exciting for genome engineering. But I dont think they quite got it, Doudna says. They kind of humored me, saying, Oh, yeah, thats nice.
On June 28, 2012, Doudnas team published its results in Science. In the paper and in an earlier corresponding patent application, they suggest their technology could be a tool for genome engineering. It was elegant and cheap. A grad student could do it.
The finding got noticed. In the 10 years preceding 2012, 200 papers mentioned Crispr. By 2014 that number had more than tripled. Doudna and Charpentier were each recently awarded the $3 million 2015 Breakthrough Prize. Time magazine listed the duo among the 100 most influential people in the world. Nobody was just humoring Doudna anymore.
Most Wednesday afternoons, Feng Zhang, a molecular biologist at the Broad Institute of MIT and Harvard, scans the contents of Science as soon as they are posted online. In 2012, he was working with Crispr-Cas9 too. So when he saw Doudna and Charpentier's paper, did he think he'd been scooped? Not at all. I didn't feel anything, Zhang says. Our goal was to do genome editing, and this paper didn't do it. Doudna's team had cut DNA floating in a test tube, but to Zhang, if you weren't working with human cells, you were just screwing around.
That kind of seriousness is typical for Zhang. At 11, he moved from China to Des Moines, Iowa, with his parents, who are engineersone computer, one electrical. When he was 16, he got an internship at the gene therapy research institute at Iowa Methodist hospital. By the time he graduated high school he'd won multiple science awards, including third place in the Intel Science Talent Search.
When Doudna talks about her career, she dwells on her mentors; Zhang lists his personal accomplishments, starting with those high school prizes. Doudna seems intuitive and has a hands-off management style. Zhang pushes. We scheduled a video chat at 9:15 pm, and he warned me that we'd be talking data for a couple of hours. Power-nap first, he said.
If new genes that wipe out malaria also make mosquitoes go extinct, what will bats eat?
Zhang got his job at the Broad in 2011, when he was 29. Soon after starting there, he heard a speaker at a scientific advisory board meeting mention Crispr. I was bored, Zhang says, so as the researcher spoke, I just Googled it. Then he went to Miami for an epigenetics conference, but he hardly left his hotel room. Instead Zhang spent his time reading papers on Crispr and filling his notebook with sketches on ways to get Crispr and Cas9 into the human genome. That was an extremely exciting weekend, he says, smiling.
Just before Doudna's team published its discovery in Science, Zhang applied for a federal grant to study Crispr-Cas9 as a tool for genome editing. Doudna's publication shifted him into hyperspeed. He knew it would prompt others to test Crispr on genomes. And Zhang wanted to be first.
Even Doudna, for all of her equanimity, had rushed to report her finding, though she hadn't shown the system working in human cells. Frankly, when you have a result that is exciting, she says, one does not wait to publish it.
In January 2013, Zhang's team published a paper in Science showing how Crispr-Cas9 edits genes in human and mouse cells. In the same issue, Harvard geneticist George Church edited human cells with Crispr too. Doudna's team reported success in human cells that month as well, though Zhang is quick to assert that his approach cuts and repairs DNA better.
That detail matters because Zhang had asked the Broad Institute and MIT, where he holds a joint appointment, to file for a patent on his behalf. Doudna had filed her patent applicationwhich was public informationseven months earlier. But the attorney filing for Zhang checked a box on the application marked accelerate and paid a fee, usually somewhere between $2,000 and $4,000. A series of emails followed between agents at the US Patent and Trademark Office and the Broad's patent attorneys, who argued that their claim was distinct.
A little more than a year after those human-cell papers came out, Doudna was on her way to work when she got an email telling her that Zhang, the Broad Institute, and MIT had indeed been awarded the patent on Crispr-Cas9 as a method to edit genomes. I was quite surprised, she says, because we had filed our paperwork several months before he had.
The Broad win started a firefight. The University of California amended Doudna's original claim to overlap Zhang's and sent the patent office a 114-page application for an interference proceedinga hearing to determine who owns Crisprthis past April. In Europe, several parties are contesting Zhang's patent on the grounds that it lacks novelty. Zhang points to his grant application as proof that he independently came across the idea. He says he could have done what Doudna's team did in 2012, but he wanted to prove that Crispr worked within human cells. The USPTO may make its decision as soon as the end of the year.
The stakes here are high. Any company that wants to work with anything other than microbes will have to license Zhang's patent; royalties could be worth billions of dollars, and the resulting products could be worth billions more. Just by way of example: In 1983 Columbia University scientists patented a method for introducing foreign DNA into cells, called cotransformation. By the time the patents expired in 2000, they had brought in $790 million in revenue.
It's a testament to Crispr's value that despite the uncertainty over ownership, companies based on the technique keep launching. In 2011 Doudna and a student founded a company, Caribou, based on earlier Crispr patents; the University of California offered Caribou an exclusive license on the patent Doudna expected to get. Caribou uses Crispr to create industrial and research materials, potentially enzymes in laundry detergent and laboratory reagents. To focus on diseasewhere the long-term financial gain of Crispr-Cas9 will undoubtedly lieCaribou spun off another biotech company called Intellia Therapeutics and sublicensed the Crispr-Cas9 rights. Pharma giant Novartis has invested in both startups. In Switzerland, Charpentier cofounded Crispr Therapeutics. And in Cambridge, Massachusetts, Zhang, George Church, and several others founded Editas Medicine, based on licenses on the patent Zhang eventually received.
Thus far the four companies have raised at least $158 million in venture capital.
Any gene typically has just a 5050 chance of getting passed on. Either the offspring gets a copy from Mom or a copy from Dad. But in 1957 biologists found exceptions to that rule, genes that literally manipulated cell division and forced themselves into a larger number of offspring than chance alone would have allowed.
A decade ago, an evolutionary geneticist named Austin Burt proposed a sneaky way to use these selfish genes. He suggested tethering one to a separate geneone that you wanted to propagate through an entire population. If it worked, you'd be able to drive the gene into every individual in a given area. Your gene of interest graduates from public transit to a limousine in a motorcade, speeding through a population in flagrant disregard of heredity's traffic laws. Burt suggested using this gene drive to alter mosquitoes that spread malaria, which kills around a million people every year. It's a good idea. In fact, other researchers are already using other methods to modify mosquitoes to resist the Plasmodium parasite that causes malaria and to be less fertile, reducing their numbers in the wild. But engineered mosquitoes are expensive. If researchers don't keep topping up the mutants, the normals soon recapture control of the ecosystem.
Push those modifications through with a gene drive and the normal mosquitoes wouldn't stand a chance. The problem is, inserting the gene drive into the mosquitoes was impossible. Until Crispr-Cas9 came along.
Emmanuelle Charpentier did early work on Crispr. Photo by: Baerbel Schmidt
Today, behind a set of four locked and sealed doors in a lab at the Harvard School of Public Health, a special set of mosquito larvae of the African species Anopheles gambiae wriggle near the surface of shallow tubs of water. These aren't normal Anopheles, though. The lab is working on using Crispr to insert malaria-resistant gene drives into their genomes. It hasn't worked yet, but if it does well, consider this from the mosquitoes' point of view. This project isn't about reengineering one of them. It's about reengineering them all.
Kevin Esvelt, the evolutionary engineer who initiated the project, knows how serious this work is. The basic process could wipe out any species. Scientists will have to study the mosquitoes for years to make sure that the gene drives can't be passed on to other species of mosquitoes. And they want to know what happens to bats and other insect-eating predators if the drives make mosquitoes extinct. I am responsible for opening a can of worms when it comes to gene drives, Esvelt says, and that is why I try to ensure that scientists are taking precautions and showing themselves to be worthy of the public's trustmaybe we're not, but I want to do my damnedest to try.
Esvelt talked all this over with his adviserChurch, who also worked with Zhang. Together they decided to publish their gene-drive idea before it was actually successful. They wanted to lay out their precautionary measures, way beyond five nested doors. Gene drive research, they wrote, should take place in locations where the species of study isn't native, making it less likely that escapees would take root. And they also proposed a way to turn the gene drive off when an engineered individual mated with a wild counterparta genetic sunset clause. Esvelt filed for a patent on Crispr gene drives, partly, he says, to block companies that might not take the same precautions.
Within a year, and without seeing Esvelt's papers, biologists at UC San Diego had used Crispr to insert gene drives into fruit fliesthey called them mutagenic chain reactions. They had done their research in a chamber behind five doors, but the other precautions weren't there.Church said the San Diego researchers had gone a step too farbig talk from a scientist who says he plans to use Crispr to bring back an extinct woolly mammoth by deriving genes from frozen corpses and injecting them into elephant embryos. (Church says tinkering with one woolly mammoth is way less scary than messing with whole populations of rapidly reproducing insects. I'm afraid of everything, he says. I encourage people to be as creative in thinking about the unintended consequences of their work as the intended.)
Ethan Bier, who worked on the San Diego fly study, agrees that gene drives come with risks. But he points out that Esvelt's mosquitoes don't have the genetic barrier Esvelt himself advocates. (To be fair, that would defeat the purpose of a gene drive.) And the ecological barrier, he says, is nonsense. In Boston you have hot and humid summers, so sure, tropical mosquitoes may not be native, but they can certainly survive, Bier says. If a pregnant female got out, she and her progeny could reproduce in a puddle, fly to ships in the Boston Harbor, and get on a boat to Brazil.
These problems don't end with mosquitoes. One of Crispr's strengths is that it works on every living thing. That kind of power makes Doudna feel like she opened Pandora's box. Use Crispr to treat, say, Huntington's diseasea debilitating neurological disorderin the womb, when an embryo is just a ball of cells? Perhaps. But the same method could also possibly alter less medically relevant genes, like the ones that make skin wrinkle. We haven't had the time, as a community, to discuss the ethics and safety, Doudna says, and, frankly, whether there is any real clinical benefit of this versus other ways of dealing with genetic disease.
Researchers in China announced they had used Crispr to edit human embryos.
That's why she convened the meeting in Napa. All the same problems of recombinant DNA that the Asilomar attendees tried to grapple with are still theremore pressing now than ever. And if the scientists don't figure out how to handle them, some other regulatory body might. Few researchers, Baltimore included, want to see Congress making laws about science. Legislation is unforgiving, he says. Once you pass it, it is very hard to undo.
In other words, if biologists don't start thinking about ethics, the taxpayers who fund their research might do the thinking for them.
All of that only matters if every scientist is on board. A month after the Napa conference, researchers at Sun Yat-sen University in Guangzhou, China, announced they had used Crispr to edit human embryos. Specifically they were looking to correct mutations in the gene that causes beta thalassemia, a disorder that interferes with a person's ability to make healthy red blood cells.
The work wasn't successfulCrispr, it turns out, didn't target genes as well in embryos as it does in isolated cells. The Chinese researchers tried to skirt the ethical implications of their work by using nonviable embryos, which is to say they could never have been brought to term. But the work attracted attention. A month later, the US National Academy of Sciences announced that it would create a set of recommendations for scientists, policymakers, and regulatory agencies on when, if ever, embryonic engineering might be permissible. Another National Academy report will focus on gene drives. Though those recommendations don't carry the weight of law, federal funding in part determines what science gets done, and agencies that fund research around the world often abide by the academy's guidelines.
The truth is, most of what scientists want to do with Crispr is not controversial. For example, researchers once had no way to figure out why spiders have the same gene that determines the pattern of veins in the wings of flies. You could sequence the spider and see that the wing gene was in its genome, but all youd know was that it certainly wasnt designing wings. Now, with less than $100, an ordinary arachnologist can snip the wing gene out of a spider embryo and see what happens when that spider matures. If its obviousmaybe its claws fail to formyouve learned that the wing gene must have served a different purpose before insects branched off, evolutionarily, from the ancestor they shared with spiders. Pick your creature, pick your gene, and you can bet someone somewhere is giving it a go.
Academic and pharmaceutical company labs have begun to develop Crispr-based research tools, such as cancerous miceperfect for testing new chemotherapies. A team at MIT, working with Zhang, used Crispr-Cas9 to create, in just weeks, mice that inevitably get liver cancer. That kind of thing used to take more than a year. Other groups are working on ways to test drugs on cells with single-gene variations to understand why the drugs work in some cases and fail in others. Zhangs lab used the technique to learn which genetic variations make people resistant to a melanoma drug called Vemurafenib. The genes he identified may provide research targets for drug developers.
The real money is in human therapeutics. For example, labs are working on the genetics of so-called elite controllers, people who can be HIV-positive but never develop AIDS. Using Crispr, researchers can knock out a gene called CCR5, which makes a protein that helps usher HIV into cells. Youd essentially make someone an elite controller. Or you could use Crispr to target HIV directly; that begins to look a lot like a cure.
Feng Zhang was awarded the Crispr patent last year. Photo by: Matthew Monteith
Orand this idea is decades away from executionyou could figure out which genes make humans susceptible to HIV overall. Make sure they dont serve other, more vital purposes, and then fix them in an embryo. Itd grow into a person immune to the virus.
But straight-out editing of a human embryo sets off all sorts of alarms, both in terms of ethics and legality. It contravenes the policies of the US National Institutes of Health, and in spirit at least runs counter to the United Nations Universal Declaration on the Human Genome and Human Rights. (Of course, when the US government said it wouldnt fund research on human embryonic stem cells, private entities raised millions of dollars to do it themselves.) Engineered humans are a ways offbut nobody thinks theyre science fiction anymore.
Even if scientists never try to design a baby, the worries those Asilomar attendees had four decades ago now seem even more prescient. The world has changed. Genome editing started with just a few big labs putting in lots of effort, trying something 1,000 times for one or two successes, says Hank Greely, a bioethicist at Stanford. Now its something that someone with a BS and a couple thousand dollars worth of equipment can do. What was impractical is now almost everyday. Thats a big deal.
In 1975 no one was asking whether a genetically modified vegetable should be welcome in the produce aisle. No one was able to test the genes of an unborn baby, or sequence them all. Today swarms of investors are racing to bring genetically engineered creations to market. The idea of Crispr slides almost frictionlessly into modern culture.
In an odd reversal, its the scientists who are showing more fear than the civilians. When I ask Church for his most nightmarish Crispr scenario, he mutters something about weapons and then stops short. He says he hopes to take the specifics of the idea, whatever it is, to his grave. But thousands of other scientists are working on Crispr. Not all of them will be as cautious. You cant stop science from progressing, Jinek says. Science is what it is. Hes right. Science gives people power. And power is unpredictable.
Amy Maxmen (@amymaxmen) writes about science for National Geographic, Newsweek, and other publications. This is her first article for WIRED.
This article appears in the August 2015 issue.
Animation by Anthony Zazzi; Illustrations by Ben Wiseman
See original here:
CRISPR-Cas.org
Welcome to the CRISPR-Cas.org webpage. This website is maintained by the Joung Lab at the Massachusetts General Hospital and will provide information and links to resources for those interested in using targetable CRISPR/Cas systems for genome engineering and other applications.
CRISPR/Cas systems are used by various bacteria and archaea to mediate defense against viruses and other foreign nucleic acid. Recent work has shown that Type II CRISPR/Cas systems can be engineered to direct targeted double-stranded DNA breaks in vitro to specific sequences by using a single "guide RNA" with complementarity to the DNA target site and a Cas9 nuclease (Jinek et al., Science 2012). This targetable Cas9-based system also works efficiently in cultured human cells (Mali et al., Science 2013; Cong et al., Science 2013) and in vivo in zebrafish (Hwang and Fu et al., in press) for inducing targeted alterations into endogenous genes.
We hope that the information provided on this webpage will be helpful to those interested in using CRISPR/Cas systems for genome engineering. Note that this webpage is currently under construction and further updates will be posted in the near future. We also welcome suggestions for additional materials about CRISPR/Cas technology not yet listed on these pages.
Read the original post:
What is CRISPR? A Beginner’s Guide | Digital Trends
}vGo)@HJZiR=}$ N(%(4w'YUXTV./zzA2|xC?.w5I29: j+N^^^V{~'hGyjA K'_zdR?N^{WO3<5OGA{?A'c^F$'IP:WIpxusoK &Yx 8G`uf&`*="o f0$3J8D:" Rs~Sk4vO+-a KeW.r=~/&cCQ4z`GtV)bQp}:H$(pe&~?v^{7[~|Oa'K`ktC0wg?4$}7w0onlS`z)5{Q+fN9l`j>s?w-/[yp}_vX6px(?ntYFs?sl&8eqn=U+,+42_*,~3rYESo3u4q? <8 @=Z Originally posted here:
Geneticists Enlist Engineered Virus and CRISPR to Battle Citrus Disease – Scientific American
Fruit farmers in the United States have long feared the arrival of harmful citrus tristeza virus to their fields. But now, this devastating pathogen could be their best hope as they battle a much worse disease that is laying waste to citrus crops across the south of the country.
The agricultural company Southern Gardens Citrus in Clewiston, Florida, applied to the US Department of Agriculture (USDA) in February for permission to use an engineered version of the citrus tristeza virus (CTV) to attack the bacterium behind citrus greening. This disease has slashed US orange production in half over the past decade, and threatens to destroy the US$3.3-billion industry entirely.
The required public comment period on the application ended last week, and the USDA will now assess the possible environmental effects of the engineered virus.
Field trials of engineered CTV are already under way. If the request is approved, it would be the first time this approach has been used commercially. It could also provide an opportunity to sidestep the regulations and public stigma attached to genetically engineered crops.
Theres a real race on right now to try to save the citrus, says Carolyn Slupsky, a food scientist at the University of California, Davis. This disease is everywhere, and its horrible.
The engineered virus is just one option being explored to tackle citrus greening. Other projects aim to edit the genome of citrus trees using CRISPRCas9 to make them more resistant to the pest, or engineer trees to express defence genes or short RNA molecules that prevent disease transmission. Local growers have also helped to fund an international project that has sequenced citrus trees to hunt for more weapons against citrus greening.
There are great scientific opportunities here, says Bryce Falk, a plant pathologist at the University of California, Davis. We need to take advantage of new technologies.
Citrus greening is caused by species from the candidate bacterial genus Candidatus Liberibacter. Spread by sap-sucking, flying insects called Asian citrus psyllids (Diaphorina citri), the bacteria cause citrus trees to make bitter, misshapen fruits that have green lower halves. The disease is also widely known by its Chinese name, huanglongbing.
The first tree in the United States with symptoms was reported in Miami in 2005. We had the uh-oh moment, says Fred Gmitter, who breeds new citrus varieties at the University of Florida in Lake Alfred.
Some researchers have had accidental success against the disease. Gmitters team released a mandarin variety called Sugarbell just as the outbreak was getting under way. Although those trees have since become infected with C.Liberibacter, farmers are able to reap a reasonable crop of sweet oranges if the plants receive proper pruning and nutrition. But it is difficult to build on that success: why the trees are relatively tolerant of the disease remains a mystery.
For years, Southern Gardens Citrus has been genetically engineering plants to express genes taken from spinach that defend against the disease. The company says that the results of field trials suggest some degree of protection. But this approach will take many years to meet regulatory requirements for marketing a genetically modified crop. And consumers may not take kindly to a fruit or juice that comes from a genetically modified tree.
So Southern Gardens Citrus added a different approach, and began the USDA approval process for engineered CTV in February. Instead of modifying the trees, the company wants to alter the genome of a harmless strain of CTV so that it produces the spinach defence gene. The company intends to graft tree limbs infected with the virus onto trees. In April, the USDA announced it would start work on an environmental impact statement, a process that typically takes about two years and will be needed before the department allows the modified virus to be used commercially.
Because the virus does not alter the fruit, this approach may allow farmers to argue that the oranges are not genetically modified, and so avoid regulation and reduce public doubt.
That is also the goal of separate projects looking for genes that confer disease resistance when switched off. If researchers can find such genes, they could use CRISPR to inactivate them. Nian Wang, a plant pathologist also at the University of Florida, is using this approach to edit orange trees, and hopes to know by 2019 whether they are disease-resistant. Others are using RNA interference in psyllids to switch off genes that allow the insects to transmit the bacteria.
For now, one question dominates: whether the citrus industry will still be alive by the time these solutions make it to the groves. Its an incredibly devastating disease, says Gmitter. Growers needed answers ten years ago.
This article is reproduced with permission and wasfirst publishedon May 16, 2017.
Read the original:
Geneticists Enlist Engineered Virus and CRISPR to Battle Citrus Disease - Scientific American
Synthego’s genetic toolkit aims to make CRISPR more accessible – TechCrunch
TechCrunch | Synthego's genetic toolkit aims to make CRISPR more accessible TechCrunch We hear a lot about the potential and implications of the gene-editing technique CRISPR, but it's not like just anyone can open up an app, pick a gene they don't like, and build the molecular machinery needed to snip it out. That's the goal, though ... Synthego aims to simplify CRISPR editing for genetic researchers Synthego Offers Free CRISPR Design Tool Synthego First to Offer Over 100000 Genomes in Powerful New CRISPR Software |
See the original post here:
Synthego's genetic toolkit aims to make CRISPR more accessible - TechCrunch
Editas delays IND for Allergan-partnered CRISPR program – FierceBiotech
Editas Medicine has delayed the target date for filing an IND for its lead candidate. The setback to the Allergan-partnered CRISPR program stems from delays at a third-party manufacturer working on Leber congenital amaurosis treatment LCA10.
Cambridge, Massachusetts-based Editas had planned to file an IND for LCA10 by the end of the year. Now Editas has delayed that major moment in its short history and that of the broader CRISPR field until the middle of next year. The delay stems from a misstep in the production of a material used in the manufacture of the adeno-associated viral (AAV) vectors Editas will use to deliver its gene editing payloads.
AAV manufacturing requires several steps to happen in perfect sequence for things to all come together. And were using several external contractors to perform these steps. We have to produce the input material that all comes together to then create the AAV in a cell culture systems, Editas CTO Vic Meyer told investors.
In our case, one of the input materials failed a quality specification and we needed to go back and remake that material. That delay in remaking the material caused us to miss the manufacturing slot with the AAV CMO and that combined with the remaking material pushed out the timeline.
The delay will potentially see Editas fall behind CRISPR Therapeutics and Intellia Therapeutics in the race to bring a CRISPR asset to the clinic. CRISPR expects to file for clearance to test its lead beta-thalassemia candidate in Europe by the end of the year. And Intellia is on track to generate the preclinical package it needs to support a FDA nod for a study of its transthyretin therapeutic by early 2018.
Shares in Editas slipped 6% in after-hours trading following the release of news of the delay. But management is seeking to spin the setback as hiding a silver lining for the longer-term prospects of the program.
It does create a window of opportunity to incorporate elements of Allergans ophthalmology preclinical development and manufacturing expertise into the program, Editas CEO Katrine Bosley said on a conference call with investors to discuss the company's first quarter results.
Editas brought Allergan on board in March, in part to tap into the ophthalmology expertise of the larger company. Allergan paid $90 million to secure an option on fiveprograms, including the lead LCA10 candidate.
See more here:
Editas delays IND for Allergan-partnered CRISPR program - FierceBiotech
Caribou Bioscience’s CEO on CRISPR’s legal and ethical challenges – TechCrunch
TechCrunch | Caribou Bioscience's CEO on CRISPR's legal and ethical challenges TechCrunch Caribou Bioscience co-founder and CEO Rachel Haurwitz joined us onstage at Disrupt this morning to help unpack some of the myriad complexities around her company's pioneering work in the field of CRISPR biology. The gene editing tool has been the ... |
Continue reading here:
Caribou Bioscience's CEO on CRISPR's legal and ethical challenges - TechCrunch
Cut Out the Hype: Gene Editing With CRISPR and the Truth about Superhuman ‘Designer Babies’ – WhatIsEpigenetics.com (blog)
Stories about a mysterious tool that can cut out and replace genes have crept out from behind the lab walls and entered boldly into the public spotlight. Nowadays, CRISPR is everywhere. And we cant help but let our imaginations wander, especially when the questions posed by this novel gene editing technology come straight out of a sci-fi movie.
Can we edit out bad genes that cause diseases in humans and replace them with healthy ones? Might parents be able to design babies to their liking, with a certain hair or eye color, personality, or intelligence level? Could we engineer animals so they cant pass on deadly diseases to us? Can we even add or remove epigenetic marks on genes of our choice to control the expression of lifes code and, perhaps, our very behavior?
The precise power of the CRISPR-Cas9 system has created exciting yet controversial opportunities for genetic and epigenetic editing. Although we certainly dont have all the answers, the intriguing questions require further exploration and a deeper look into the near and distant possibilities for our society. As endless as the opportunities may appear to scientists and laypeople alike, some are more realistic than others. Its crucial we trim the hype from the realistic capabilities of CRISPR, as we usher in what some may call the golden age of genetic engineering.
The start of CRISPR
You know when you pick up a suspense novel, and read the first chapter, and you get a little chill, and you know, Oh, this is going to be good? It was like that. Jennifer Doudna, Ph.D. Credit:The New York Times.
Since the beginning of CRISPRs recent discovery as a precise and simple gene editing method, interest in its potential to improve our quality of life has skyrocketed, and with no end in sight. A similar excitement was expressed by one of the co-inventors of CRISPR, Jennifer Doudna from University of California Berkeley.
In 2011, Doudna was approached at a microbiology conference in Puerto Rico by a researcher from Max Planck Institute for Infection Biology, Emmanuelle Charpentier. The two started a conversation that laid the ground work for arguably one of the greatest collaborations, which spurred the invention of CRISPR.
I had this feeling. You know when you pick up a suspense novel, and read the first chapter, and you get a little chill, and you know, Oh, this is going to be good? It was like that, Doudna told The New York Times in 2015.
Surprisingly, the investigation of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) in bacteria is not a new thing. Researchers have been exploring these repeated sequences since the 1980s, but their function was unknown at the time. Then, scientists slowly started to uncover clues about their purpose, which pointed to a built-in adaptive immune system that bacteria used to combat invaders such as viruses.
Within the past few years, researchers like Jennifer Doudna and Emanuelle Charpentier, along with postdoc researcher Martin Jinek, have been tapping into the gene-editing possibilities of the CRISPR-Cas9 system. Meanwhile, Feng Zhang from the Broad Institute and MIT was eager to show that the system worked in mouse and human cells, which he accomplished in his paper published in 2013. He even created an alternative genome engineering method called CRISPR-Cpf1, which may improve the tools precision and power.
Recently, the two groups of researchers entered a fiery battle for a CRISPR patent and the scientific community called for a moratorium on using CRISPR to edit the human germline for fear of unknown repercussions as a result of making heritable changes that could shift the gene pool. It will surely be intriguing to follow the progression of this gene editing system and its uncertain what the future holds.
How it works
The CRISPR-Cas9 system targets precise gene sequences and removes, adds to, or changes them with the help of two components: an enzyme called Cas9 and guide RNA (gRNA). Its based on the naturally occurring ability of bacteria to recognize and destroy invading viruses via a genetic memory.
SEE ALSO: An Epigenetic Link Between Memory Loss and Epilepsy
Cas9 acts as the scissor that snips the DNA and the RNA guide is a tailor-made sequence that ensures Cas9 is cutting in the right place. Researchers are able to program the guide RNA with any sequence of the genetic code they desire in order to lead Cas9 to the proper location.
Other techniques for editing DNA, such as TALENs and zinc finger nucleases were explored by researchers around the same time, but these methods have a much lower level of precision and are significantly more cumbersome. Unlike other techniques, CRISPR can even target multiple genes at once. The beauty of this gene editing system is how relatively simple, accessible, and incredibly precise it is. However, even among the accomplishments there are certainly limitations.
CRISPR accomplishments
As young as the technology is, scientists have been working feverishly with the CRISPR-Cas9 system in several applications. In one study published in PNAS, a group of researchers edited out a gene sequence in mosquitos and replaced it with a DNA segment that rendered them resistant to the parasite that causes malaria, known as Plasmodium falciparum. This could prevent mosquitos from transmitting the disease to humans entirely. Interestingly, when these malaria-resistant genetically modified mosquitos mated, they passed on the resistance to nearly 99% of their offspring. This was true even if a modified mosquito bred with a normal one.
A study conducted by a Chinese research team led by geneticist Lei Qu at Yulin University also demonstrated the successful use of CRISPR to bulk up livestock. They manipulated goats DNA to make them more muscular and produce more wool, in the hopes of bolstering the goat meat and cashmere sweater industry in Shaanxi, China. We believed gene-modified livestock will be commercialized after we demonstrate [that it] is safe, Qu predicted in an article by Scientific American.
Another group of researchers were able to edit out a genetic mutation in mice that causes a disease known as retinitis pigmentosa (RP), which can ultimately lead to blindness. Although not yet approved for use in humans, they were able to restore the mices vision and are hopeful for its therapeutic application in people. They recently published their results in Nature.
Not only can scientists edit genes using CRISPR, but they may be able to change the epigenome using CRISPR as well. Many diseases are not caused by a single genetic mutation but rather disturbed gene expression profiles. Harnessing the ability to edit epigenetic marks could drastically broaden our ability to cure a much wider range of disorders. In theory, perhaps editing our epigenome could allow us to cherry-pick more desirable behaviors.
Researchers can also utilize the power of next generation sequencing to perform chromatin immunoprecipitation sequencing (ChIP-seq) with a CRISPR/Cas9 antibody. The precise, high throughput capability of this method is especially promising because of the target efficiency of the Cas9 enzyme in conjunction with multiple guide RNAs, which can be used simultaneously for multiplexing. Not only can ChIP-seq be useful as an unbiased method for detecting on-target effects of the CRISPR-Cas9 gene editing system, but it might also be used to pinpoint how the system might miss the mark, which would be helpful when developing the system for therapeutic application.
Recently, researchers used the CRISPR-Cas9 system to add acetyl groups to histones, carrying enzymes to certain locations on the genome. Histone modifications, including histone acetylation and histone methylation, have the ability to remodel chromatin to make genes more or less accessible, influencing their expression. Other research suggests we may modify DNA methylation with CRISPR-Cas9, which could prove invaluable for understanding and treating disorders that are linked to this epigenetic modification, such as cancer, lupus, muscular dystrophy, and many others.
Although these studies have been conducted in animal models and the only CRISPR-Cas9 research on non-viable human embryos was performed in China, there is much more to be learned about the effects of CRISPR in humans and how it might be used towards creating what has gained a lot of attention recently superior designer babies.
Continue to the next page to read about designer babies and future directions.
Continued here:
Will CRISPR Technology Create a New "Human" Species? – Big Think
Why Are So Many Musical Geniuses Asocial? A New Study Reveals an Interesting Link
Will CRISPR Technology Create a New "Human" Species?
How This Couple Turned Teens' Love of Texting Into Love for Reading Books
US author T.C. Boyle presents his new book 'The Women' at the Leipzig Book Fair on March 13, 2009. (Photo by JENS SCHLUETER/AFP/Getty Images)
T.C. Boyle will read his short story "Are We Not Men?" at the Los Angeles Hope Festival on Sunday, May 21. The event is free but seats are limited. RSVP here.
American author TC Boyle, who has aptly been described as "a punk Mephistopheles," talks casually about death and suicide. His interview with Big Think begins, "There is no hope whatsoever. Our species will be extinguished probably in a couple of generations, maybe even before that depending upon the microbes of the world." Yet Boyle exhibits robust mental health, maintaining an orderly writing schedulefour to five hours per day, always in the morningand a stable life, both with respect to his family and his career as a Professor of English at the University of Southern California.
Describing his short story "Are We Not Men?" Boyle says:
tc-boyle-on-writing-and-the-human-animal
"It's about CRISPR technology, which obsesses me. This is a gene editing technology which makes it much easier to edit genes in other species. In fact, if you subscribe to Nature and Science as I do for the past year there's a huge ad right in the beginning of a boxing glove on a fist and it says knock out any gene. They're selling kits to amateurs to anybody to play with various bacteria and gene edit these bacteria. Is this a good idea? I don't think so. And of course, in my telling we're just projecting slightly into the future, when we can make new species. Not to mention the parent who wants to get his kid into the best school. Give me a break. I mean it will be like buying a new car when you have a kid. You go you see how the genes line up and you pick whoever you want. You want eight foot tall? You want orange eyes? You want somebody who can run the hundred-yard dash in nine seconds? That's what it's coming to. So we're not going to be humans anymore, which I guess is no great loss."
Born Thomas John Boyle, TC changed his middle name toCoraghessan at the age of 17. As a writer, he matured at the Iowa Writer's Workshop in the 1970s, staying on after earning his MFA to complete aPhd in 19th century British Literature. While in Iowa, he forged a friendship with Raymond Carver, the best short story writer of a generation, although their two writing styles were dissimilar.
Boyle released his 26th book, The Terranauts, in October of 2016. Below is the full schedule for the Los Angeles Hope Festival.
MOST POPULAR
Top Vets Urge Dog Owners to Stop Buying Pugs and Bulldogs
4 Things You Can Do to Cheer Up, According to Neuroscience
When You Can't Afford to Make a Mistake, Thisll Keep You Sharp
Study Finds Link Between Brain Damage and Religious Fundamentalism
The rest is here:
Will CRISPR Technology Create a New "Human" Species? - Big Think
Intellia moves closer to clinic with CRISPR tech – FierceBiotech
Intellia Therapeutics has taken another step towardhuman trials of its gene editing technology after reporting new data in animal models.
The CRISPR specialist says it has been able to show for the first time that it is able to not only achieve long-term suppression of a gene using its gene-editing CRISPR/Cas9 drug, in this case the sequence coding for serum transthyretin (TTR) protein, but also demonstrate a dose-dependent reduction in the activity of the target gene in a second animal species.
New data from studies in mice show that a previously reported 97% reduction in TTRdriven by 70% gene editing efficiency working in mouse liverslasts for up to six months from a single dose. Meanwhile, a study in rats showed a similar dose-dependent reduction in the TTR gene, and crucially evidence of comparable activity in a second species as Intellia builds the case to move to the clinic.
In this test, a single intravenous infusion resulted in 66% gene editing in the rat liver and up to 91% reduction in serum TTR protein levels. Crucially, the results also backed up earlier data showing the CRISPR drug is rapidly cleared from the body, desirable as it reduces the chances of off-target effects that could cause toxicity. Both datasets were reported at the American Society of Gene & Cell Therapys Annual Meeting (ASGCT) in Washington D.C. over the weekend.
Senior VP David Morrissey said the rat study "validates the in vivo CRISPR/Cas9 platform using Intellia's proprietary LNP delivery system," adding that it shows "the ability to expand out studies in larger species.
Under FDA rules, companies typically need data in at least two animal speciesincluding one non-rodent speciesbefore they can progress into human studies. The new data keeps Intellia on course to complete the work needed to get FDA approval for trials of its TTR therapeutic in early 2018.
Companies like Intellia, Editas and CRISPR Therapeutics are vying to bring the CRISPR technology into the clinic, potentially generating one-dose therapies that could cure a host of gene-related diseases, although they will not be the first groups to do so.
Last year, Chinese scientists from Sichuan University's West China Hospital made history when they used CRISPR for the first time on an adult with lung cancer, using cells harvested from the patient that had been genetically modified using CRISPR to remove a brake (PD-1) on the immune response to the tumor. And at the end of April, a second Chinese team from Nanjing University's Nanjing Drum Tower Hospital tested a similar procedure in a patient with head and neck cancer.
More here:
Intellia moves closer to clinic with CRISPR tech - FierceBiotech
Coming age of CRISPR gene editing: What in heck is the ‘Pink Chicken Project’? – Genetic Literacy Project
A new website called the Pink Chicken Project offers up an intriguing nugget of an idea: what if we turned all chickens on Earth pink? Yes, you read that right. The creators of the project told Motherboard in an email that they are a small group of designers and engineers with an interest in biotechnology, and say they want to genetically modify chicken DNA so future domestic birds will be born with pink bones and pink feathers. Right now, though, the project appears to be little more than an artistic concept (complete with some photos of neon pink chicken meat, eggs, and bones).
The modification would supposedly be done using the gene editing technique CRISPR, with adoption of the pink color accelerated by a gene drive, a mechanism for increasing the odds an offspring will inherit a traitsuch as the color pinkfrom its parents. The pink color would come from cochineals, a little bug commonly used in food dye. The bug produces a chemical called carminic acid, which combines with calcium in bones to form a dye.
Why would anyone want to do this? According to the projects website, we should leave reminders for future generation of humanitys impact on the environmentin the form of discarded pink chicken bones.
The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post:These People Want to Genetically Engineer Pink Chickens
Continue reading here:
Pac-Man like CRISPR enzymes discovered – Lab News
New CRISPR enzymes have been found that could be used as sensitive detectors for infectious viruses.
US scientists were able to show that once CRISPR-Cas13a binds to its target RNA, it indiscriminately cuts up all RNA, like Pac-Man eating dots. Jennifer Doudna, professor of molecular biology and of chemistry at the Broad Institute, in Massachusetts, said: Our intention is to develop the Cas13a family of enzymes for point-of-care diagnostics that are robust and simple to deploy.
Researchers at the Institute paired CRISPR-Cas13a with RNA amplificationand showed the system, dubbed SHERLOCK, could detect viral RNA at extremely low concentrations. This included RNA linked to a reporter molecule that would fluoresce, allowing it to be detected. The system has been shown to detect the presence of dengue and Zika viral RNA and potentially could detect RNA of distinctive cancer cells.
The CRISPR-Cas13a family, formerly referred to as CRISPR-C2c2, is related to CRISPR-Cas9, which is already revolutionising biomedical research and treatment because of the ease of targeting it to unique DNA sequences to cut or edit. While the Cas9 protein cuts double-stranded DNA at specific sequences, the Cas13a protein a nucleic acid-cutting enzyme referred to as a nuclease latches onto specific RNA sequences, and not only cuts that specific RNA, but runs amok to cut and destroy all RNA present.
Alexandra East-Seletsky, a UC Berkeley graduate student working in the laboratory of Jennifer Doudna, one of the inventors of the CRISPR-Cas9 gene-editing tool, said: We have taken our foundational research a step further. We found other homologs of the Cas13a family that have different nucleotide preferences, enabling concurrent detection of different reporters with, say, a red and a green fluorescent signal, allowing a multiplexed enzymatic detection system.
While the original Cas13a enzyme used by the University of California Berkeley and Broad teams cuts RNA at one specific nucleic acid, uracil, three of the new Cas13a variants cut RNA at adenine. This difference allows simultaneous detection of two different RNA molecules, which could be from two different viruses.A full report of their findings will appear in Molecular Cell.
East-Seletsky said: Think of binding between Cas13a and its RNA target as an on-off switch target binding turns on the enzyme to go be a Pac-Man in the cell, chewing up all RNA nearby. This RNA killing spree can kill the cell.
UC Berkeley researchers in Nature last September argued the Pac-Man activity of CRISPR-Cas13a is its main role in bacteria, aimed at killing infectious viruses or phages. As part of the immune system of some bacteria, it allows infected cells to commit suicide to save their sister microbes from infection. Similar non-CRISPR suicide systems exist in other bacteria.
The UC Berkeley researchers subsequently searched databases of bacterial genomes and found 10 other Cas13a-like proteins. These have been synthesised and studied to assess their ability to find and cut RNA. Of those, seven resembled the original Cas13a, while three differed in where they cut RNA.
East-Seletsky said: Building on our original work, we now show that it is possible to multiplex these enzymes together, extending the scope of the technology. There is so much diversity within the CRISPR-Cas13a family that can be utilised for many applications, including RNA detection.
By Dermot Martin
Go here to read the rest:
Intellia Therapeutics Announces Progress with CRISPR/Cas9 at the American Society of Gene & Cell Therapy Annual … – GlobeNewswire (press…
May 13, 2017 08:40 ET | Source: Intellia Therapeutics, Inc.
WASHINGTON, May 13, 2017 (GLOBE NEWSWIRE) -- Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on the development of potentially curative therapeutics using CRISPR technology, presented an update on its long-term mouse genome editing and delivery studies and shared new, first-time data in rat models demonstrating consistent dose-dependent editing, at the American Society of Gene & Cell Therapys Annual Meeting (ASGCT).
These data, featured in a platform presentation on Saturday, May 13 at ASGCT showed:
Data from the additional rat study further validates the in vivo CRISPR/Cas9 platform using Intellias proprietary LNP delivery system, said David Morrissey, Ph.D., senior vice president, Platform and Delivery Technology. In both species, we saw unprecedented in vivo liver editing results and consistent delivery of CRISPR/Cas9 with systemic administration using LNPs, while also showing the ability to expand our studies in larger species.
About Intellia Therapeutics
Intellia Therapeutics is a leading genome editing company focused on the development of proprietary, potentially curative therapeutics using the CRISPR/Cas9 system. Intellia believes the CRISPR/Cas9 technology has the potential to transform medicine by permanently editing disease-associated genes in the human body with a single treatment course. Our combination of deep scientific, technical and clinical development experience, along with our leading intellectual property portfolio, puts us in a unique position to unlock broad therapeutic applications of the CRISPR/Cas9 technology and create a new class of therapeutic products. Learn more about Intellia Therapeutics and CRISPR/Cas9 at intelliatx.com; Follow us on Twitter @intelliatweets.
Forward-Looking Statements
This press release contains "forward-looking statements" of Intellia within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, express or implied statements regarding Intellias ability to advance and expand the CRISPR/Cas9 technology to develop into human therapeutic products; our ability to achieve stable liver editing; effective genome editing with a single treatment dose; and the potential timing and advancement of our preclinical studies and clinical trials. Any forward-looking statements in this press release are based on managements current expectations and beliefs of future events, and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: risks related to Intellias ability to protect and maintain our intellectual property position; risks related to the ability of our licensors to protect and maintain their intellectual property position; uncertainties related to the initiation and conduct of studies and other development requirements for our product candidates; the risk that any one or more of Intellias product candidates will not be successfully developed and commercialized; the risk that the results of preclinical studies will be predictive of future results in connection with future studies; and the risk that Intellias collaborations with Novartis or Regeneron will not continue or will not be successful. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause Intellias actual results to differ from those contained in the forward-looking statements, see the section entitled Risk Factors in Intellias most recent annual report on Form 10-K filed with the Securities and Exchange Commission, as well as discussions of potential risks, uncertainties, and other important factors in Intellias subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Intellia Therapeutics undertakes no duty to update this information unless required by law.
Related Articles
Intellia Therapeutics, Inc.
Cambridge, Massachusetts, UNITED STATES
Intellia Therapeutics, Inc. Logo
LOGO URL | Copy the link below
Formats available:
See the original post here:
CRISPR: The Future of Medicine and Human Evolution – in-Training
by Tim Beck at Drexel University College of Medicine
Humanitys unnerving cruelty is perhaps only balanced by its kindness and innovation. It remains to be seen on which side of the scale CRISPR, a remarkable genome-editing tool and one of the most exciting scientific innovations of the 21st century,will land.
In their monumental 1953 Nature paper stretching over little more than one glorious page and including only a simple diagrammatic illustration and a fuzzy x-ray image Nobel laureates James Dewey Watson and Francis Harry Compton Crick proclaimed the following, We wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.). This structure has novel features which are of considerable biological interest. Of considerable biological interest, indeed, and a critical aspect of the discovery of CRISPR.
The Human Genome Project (HGP) taught us how to read long stretches of Watson and Cricks miraculous DNA double-helix: it taught us how to read the code of life. CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9) is the most recent step along the path towards absolute control over the human genome. CRISPR provides us with the ability to edit the code of life seemingly at will.
In the most basic of terms, CRISPR can recognize specific DNA sequences, using complementary guide RNA and recruit cutting-enzymes (e.g., the endonuclease Cas9), which precisely cut-out the targeted piece of genetic material. Under the right conditions, the cut region is subsequently filled-in with new DNA by the cells normal DNA-repair machinery.
The scientists to unlock the full genomic-editing potential of CRISPR (expanding on the work of numerous other great scientists), and likely future Nobel-laureates, Jennifer Doudna (Berkeley, California), Emmanuelle Charpentier (Max Planck Institute for Infection Biology, Berlin) and Feng Zhang (Broad MIT), published two papers in quick succession in 2012/13, describing the remarkable capability of CRISPR to precisely and reliably (to varying degrees) edit the genomes of cells, including of mammalian cells.
The promise of CRISPR technology is highlighted by the contentious ongoing patent dispute between Berkley and Broad, to clarify who discovered what when and who holds the rights to technology estimated to be worth billions of dollars.
Why is this technology worth billions of dollars? For one, think about every genetic disease you have ever heard of. Did cystic fibrosis (CF) come to mind? Do you know anyone with Tay-Sachs Disease? Duchenne Muscular Dystrophy, going once, going twice, sold to the fastest gene-editor. In theory, by combining in vitro fertilization with CRISPR technology, every known hereditary single-gene disease (you may have noticed that the above examples are all generally caused by single gene mutations) can be eliminated. Not in a year from now. Not tomorrow. Today!
Chinese researchers have validated that CRISPR/Cas9 can be used to alter human embryos, and recently Kang et al. (The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China) used CRISPR to cure human embryos of beta-thalassemia and glucose-6-phosphate-dehydrogenase (G6PD) deficiency. The success rate (i.e., the percent of embryos that were successfully altered using CRISPR) varied significantly between studies, a concerning aspect of the technology that is likely going to be optimized rapidly, considering that CRISPR has only been in the scientific mainstream for a few short years.
Eradicating more complex diseases in embryos is a bit more complicated and will take some time. Editing genomes to treat cancer, for example, in mature individuals will also take a bit more time. However, the FDA approved a clinical trial in 2016 to test the potential of CRISPR as a tool to enhance the ability of immune cells modified outside the body, similar to the idea of modifying embryos in vitro to destroy cancer cells.
There are ethical challenges to consider. Luminaries like David Baltimore, Paul Berg and others have described these challenges in detail and have proposed appropriate steps to consider. Changes to the genome are of course permanent and as such are potentially passed on from generation to generation (i.e., changes made to an embryo are potentially passed on to subsequent offspring). Evolution at the speed of light if you will. Would it be possible to use CRISPR to create super-humans? To implant kill-switches into human cells? To prolong the lives of those that can pay for it?
The decision in February of 2016 by the UK Human Fertilisation and Embryology Authority (HFEA) to grant permission to UK researchers to edit the genome of human embryos is emblematic of the global embrace of CRISPR. Even in the US, a country generally less accommodating when it comes to research on human embryos, an international committee convened by the U.S. National Academy of Sciences (NAS) and the National Academy of Medicine concluded earlier this year that editing the DNA of a human embryo to prevent disease could be ethically permissible under the right set of circumstances.
If nothing else, history (Robert Oppenheimers opinion on the matter would be intriguing) has taught us that world-altering technologies like CRISPR cannot be un-invented. We all have front row seats to watch in awe as CRISPR transforms medicine, science and perhaps human evolution itself. Our best hope is to educate each other, to stay informed and to try to minimize the abuse of a tool powerful enough to re-write the code of life and the future of humanity.
Medical Student Editor
Drexel University College of Medicine
I am an MD/PhD Candidate at Drexel University College of Medicine/Fox Chase Cancer Center. My research focuses on cancer cell signaling, drug resistance, cancer cell invasion and discovery of prognostic biomarkers. Politics (national and international), foreign affairs and healthcare policy are additional topics I am particularly interested in.
Read more here:
CRISPR: The Future of Medicine and Human Evolution - in-Training
What You Need to Know About the New CRISPR Cancer Treatment – BOSS Magazine
Share on Pinterest Pin it
Share on Google Plus Plus
The researchers at the University of Pittsburgh have just used the CRISPR-Cas9 genome editing system to forever revolutionize the fight against cancer.
The treatmentwhen used on micewas shown to shrink aggressive tumors and increase survival rates without harming healthy cells. Meaning only cancer cells are attacked, effectively leaving healthy cells unharmed.
CRISPR Cancer Treatment Explained The CRISPR cancer treatment targets fusion genes, which are mutations created when two genes combine to form one hybridoften leading to cancer.
Previously, researchers found MAN2A1-FER, a fusion gene known to be associated with prostate, liver, lung, and ovarian cancer. It also contributes to thegrowth and spread of these tumors.
The unique DNA fingerprint of fusion genes could, however, be its own downfall with the CRISPR cancer treatment targeting specific DNA sequences. The treatment seeks out fusion gene patterns and replaces them with cancer-killing ones.
This is the first time that gene editing has been used to specifically target cancer fusion genes, saidJian-Hua Luo, lead author of the study. Luo added:
The tool lays the groundwork for what could become a totally new approach to treating cancer. Other types of cancer treatments target the foot soldiers of the army. Our approach is to target the command center, so there is no chance for the enemys soldiers to regroup in the battlefield for a comeback.
To test the technique, Luos team transplanted human liver and prostate cancer cells into mice and treated one group with the CRISPR cancer tool to target those fusion genes. The second group was given the same treatment targeting fusion genes that they didnt carry.
From the first group, the mices tumors shrunk up to 30 percent, didnt spread to throughout the body, and all the mice survived the eight-week test.
Meanwhile, the second group had the mices tumors grow nearly 40 times larger, spreading to other parts of the body in most cases. None of the mice in this group made it to the end of the test period.Big Plans For CRISPR-Cas9 The genome editing system has already proven itself to be an incredible tool, giving us new and amazing ways to battle muscular dystrophy, blindness, and HIV.
By also editing human immune cells to more efficiently battle cancer cells, the CRISPR cancer treatment has now been used in human trials.
It truly is an exciting time in the world of medical research as developments continue showing that the CRISPR cancer technique can remit cancer cells.
Despite this, researchers have bigger plans for the CRISPR cancer technique. They plan on testing further in hopes of completely eradicating cancer.
View original post here:
What You Need to Know About the New CRISPR Cancer Treatment - BOSS Magazine
Oxford Genetics licenses CRISPR tech to power synbio push – FierceBiotech
Oxford Genetics has licensed CRISPR gene editing technology from ERS Genomics. The agreement gives the British synthetic biology service provider the right to use CRISPR technology to improve gene therapy viral vectors and develop cell lines.
Oxford, United Kingdom-based Oxford Genetics has secured the nonexclusive rights to the CRISPR intellectual property. Oxford Genetics plans to use the technology to provide genome engineering services and support its cell line development and gene therapy viral vector R&D efforts. The agreement also clears Oxford Genetics to use the CRISPR-edited cells lines in the production of biotherapeutics. And to use CRISPR to develop research tools and reagents for sale.
News of the agreement comes almost exactly three years after Horizon Discovery licensed CRISPR intellectual property from ERS Genomics for use in similar applications. The nonexclusive deal between ERS Genomics and Horizon Discoverywhich is based 70 miles away from Oxford Genetics in Cambridgegave the genomics research business the right to use CRISPR to develop research tools, kits and reagents and in other applications.
ERS Genomics was cofounded by Emmanuelle Charpentier, Ph.D., one of the key players in the story of the discovery of the CRISPR-Cas9 immune system and its role in cleaving DNA. Charpentier set up the organization to facilitate access to the CRISPR-Cas9 intellectual property she holds. The firm is on the same side of the CRISPR patent dispute as CRISPR Therapeutics, Intellia Therapeutics and Caribou Biosciences. Together, the companies are appealing the U.S. patent boards ruling in the Broad Institute case.
The ruling looked at the question of whether the it was obvious to apply CRISPR to eukaryotic cells, such as the CHO and HEK293 cell lines Oxford Genetics uses in its cell line development services. But the uncertainty created by the ongoing patent dispute has not stopped Oxford Genetics from striking a deal to add CRISPR to its arsenal.
Licensing the CRISPR gene editing technology from ERS Genomics is another step on our journey to establishing the most efficient and integrated service portfolio in this sector. We are excited to be adding this technology to our existing portfolio in the synthetic biology space and supporting the rapidly expanding market for products and services that utilise genome engineering technologies, Paul Brooks, Ph.D., chief commercial officer at Oxford Genetics, said in a statement.
See the original post:
Oxford Genetics licenses CRISPR tech to power synbio push - FierceBiotech
Cambridge gene editing firm CRISPR to use delivery tech honed … – Boston Business Journal
Boston Business Journal | Cambridge gene editing firm CRISPR to use delivery tech honed ... Boston Business Journal Cambridge gene editing biotech CRISPR Therapeutics has grabbed an exclusive license from MIT to use a delivery system that could make such treatments ... -$0.51 Earnings Per Share Expected for Crispr Therapeutics AG (CRSP) This Quarter Crispr Therapeutics AG (CRSP) Given Average Recommendation of "" by Analysts Rodger Novak Sells 49384 Shares of Crispr Therapeutics AG (CRSP) Stock |
Continue reading here:
Cambridge gene editing firm CRISPR to use delivery tech honed ... - Boston Business Journal
Update: CRISPR – Radiolab
It's been almost two years since we learned about CRISPR, a ninja-assassin-meets-DNA-editing-tool that has been billed as one of the most powerful, and potentially controversial, technologies ever discovered by scientists. In this episode, we catch up on what's been happening (it's a lot), and learn about CRISPR's potential to not only change human evolution, but every organism on the entire planet.
Out drinking with a few biologists, Jad finds out about something called CRISPR. No, its not a robot or the latest dating app, its a method for genetic manipulation that is rewriting the way we change DNA. Scientists say theyll someday be able to use CRISPR to fight cancer and maybe even bring animals back from the dead. Or, pretty much do whatever you want. Jad and Robert delve into how CRISPR does what it does, and consider whether we should be worried about a future full of flying pigs, or thesimple fact that scientists have now used CRISPR to tweak the genes of human embryos.
This episode was reported and produced by Molly Webster and Soren Wheeler. Special thanks to Jacob S. Sherkow.
Read more from the original source:
CRISPR gene-editing tool targets cancer’s "command center" – Gizmag – New Atlas
Researchers have used CRISPR-Cas9 to target DNA sequences specific to cancer, shrinking tumors and improving the survival rates of cancer-stricken mice (Credit: vchalup2/Depositphotos)
The CRISPR-Cas9 genome editing system can do some pretty amazing things, giving us new ways to fight muscular dystrophy, blindness, and even HIV. But at the top of its hit list is cancer, and now researchers from the University of Pittsburgh have used the tool to target what they call cancer's command center, in a treatment that's been shown in mice to shrink aggressive tumors and increase survival rates without harming healthy cells.
The technique works by targeting fusion genes, mutations created when two separate genes combine into one hybrid that often leads to cancer. In previous work, the team found that a fusion gene known as MAN2A1-FER was associated with cancer of the prostate, liver, lungs and ovaries, and it helps the tumors grow and spread.
Upgrade to a Plus subscription today, and read the site without ads.
It's just US$19 a year.
But the unique DNA fingerprint of fusion genes could be their own undoing. CRISPR-Cas9 is used to target specific DNA sequences and replace them with something else, so delivering the gene editing tool through viruses, the researchers were able to seek out these fusion gene patterns and replace them with cancer-killing genes instead. The other upside is that, unlike conventional treatments like chemotherapy, the new approach will only attack cancer cells, leaving healthy cells undamaged.
In the University of Pittsburgh study, the team transplanted human prostate and liver cancer cells into mice, then treated one group with the CRISPR tool that targets those fusion genes. As a result, the tumors shrunk by up to 30 percent, didn't spread through the body, and the animals all survived to the end of the eight-week test. Meanwhile, in a control group that received the same treatment targeting fusion genes that weren't present in their bodies, the tumors grew almost 40 times larger and in most cases, spread to other parts of the body. None of the control group survived to the end of the test period.
CRISPR-Cas9 has already been put to work in human trials, but these involved editing human immune cells to better fight cancer. The new technique goes over the heads of the "foot soldiers" of the battle and instead targets the "command center" directly.
"This is the first time that gene editing has been used to specifically target cancer fusion genes," says Jian-Hua Luo, lead author of the study. " It is really exciting because it lays the groundwork for what could become a totally new approach to treating cancer. Other types of cancer treatments target the foot soldiers of the army. Our approach is to target the command center, so there is no chance for the enemy's soldiers to regroup in the battlefield for a comeback."
While the current work shows that the technique can cause the cancer cells to go into remission, the researchers plan to test whether it could be used to completely wipe it out instead.
The research was published in the journal Nature Biotechnology.
Source: University of Pittsburgh
Read this article:
CRISPR gene-editing tool targets cancer's "command center" - Gizmag - New Atlas
New CRISPR Technique Can Potentially Stop Cancer In Its Tracks – Wall Street Pit
In a study recently published online on Nature Biotechnology, University of Pittsburgh School of Medicine researchers report that a new technique using the CRISPR-Cas9 genome editing technology effectively targets cancer-causing fusion genes and improves survival in mouse models of aggressive liver and prostate cancers.
Professor of pathology at Pittsburghs School of Medicine, Jian-Hua Luo, M.D., Ph.D., explains that this is the first time that gene editing has been used to specifically target cancer fusion genes. The professor also adds that this is really exciting because it paves the way for what could become an entirely new approach to cancer treatment.
Fusion genes are hybrid genes formed from two previously separate genes. This fusion can occur as a result of gene translocation, interstitial deletion, or chromosomal inversion, and produce abnormal proteins that can cause or accelerate cancer growth. In short, these fusion genes are often associated with cancer.
A panel of fusion genes responsible for recurrent and aggressive prostate cancer has been previously identified by Dr. Luo and his team. Earlier this year, in a study published on Gastroenterology, they described how one of these fusion genes, known as MAN2A1-FER, can be found in other types of cancer, such as that of the lungs, ovaries, liver, and is also responsible for rapid tumor growth and invasiveness.
As described in a press release, for this study, the team used CRISPR-Cas9 to target unique DNA sequences formed as a result of fusion genes. The process involves the use of viruses to deliver gene editing tools that remove the mutated DNA of the fusion gene, then replacing it with genes that cause cancer cells to die.
Because fusion genes are only present in cancer cells and not healthy cells, the gene therapy is quite specific. In contrast with present cancer treatments such as chemotherapy which indiscriminately attacks both cancerous and healthy cells, this new approach will be much more preferable because it only attacks cancerous cells and leaves healthy cells intact.
To conduct the study, the team used mouse models which received transplants of human prostate and liver cancer cells. This group of mice was treated with the CRISPR gene editing tool. After the 8-week treatment period, their tumors shrunk by up to 30%, did not spread throughout their bodies, and all of them survived.
On the other hand, in a control group which was treated with viruses that target a kind of fusion gene that wasnt present in tumors, the results were a stark contrast. The mice had tumors growing almost forty times bigger. And in most cases, the tumors spread to other parts of their bodies. Most importantly, none among the group survived.
The findings suggest a new and different way to attack cancer. As Dr. Luo explained, Other types of cancer treatments target the foot soldiers of the army. Our approach is to target the command center, so there is no chance for the enemys soldiers to regroup in the battlefield for a comeback.
Dr. Luo also notes that another advantage of their approach over existing cancer treatments is that it is highly adaptive, not to mention target-specific. Going forward, they plan to test whether their strategy can do more than just stop or delay the spread of the disease. The aim of course, is to hopefully one day completely eradicate it.
See the rest here:
New CRISPR Technique Can Potentially Stop Cancer In Its Tracks - Wall Street Pit
A cancer gene also grows stem cells, CRISPR in monkey embryo … – Speaking of Research
Speaking of Research | A cancer gene also grows stem cells, CRISPR in monkey embryo ... Speaking of Research Welcome to this week's Research Roundup. These Friday posts aim to inform our readers about the many stories that relate to animal research each week. How To Beat Cancer? CRISPR Stares Into Its Eyes Then Snips Out ... Genetic Engineering: We Can, But Should We? - Veritas News |
Link:
A cancer gene also grows stem cells, CRISPR in monkey embryo ... - Speaking of Research
CRISPR Could Transform the Way We Diagnose Disease – Gizmodo
A diagnostic test for detecting Zika with CRISPR. Image: Wyss Institute
The gene editing tool CRISPR could one day mean that we can simply edit away disease, blight and undesirable genetic traits. Now, its also gaining traction in another realm of medical technology: diagnosing disease.
On Thursday, researchers at UC Berkeley announced that theyve discovered ten new CRISPR enzymes that can potentially be used to diagnose diseases like Zika or dengue fever quickly and cheaply. The technology isnt ready for prime-time yet, but it could eventually allow clinics to test a sample of someones blood, saliva, or urine for many diseases at once.
Typically, when people talk about CRISPR, they are actually talking about CRISPR-Cas9. Thats the CRISPR programming paired with one specific enzyme (Cas9) thats used to DNA at precise locations. But there are a host of other enzymes out there that can be used as part of the CRISPR system, and all of them have different talents. The new enzymes that Berkeley researchers have discovered are all variants of the CRISPR protein Cas13a, and their speciality seems to be detecting specific sequences of RNA, including those from a virus.
In genetic engineering, CRISPR is used to home in precisely on a specific piece of DNA, cut it, and put it back together with the desired genetic code. Here, the same principle is at work. Only instead of sending CRISPR to sniff out a specific piece of DNA, it hunts for RNAthe carbon copy of DNA used to make proteinsassociated with a specific virus present in someones blood, urine, saliva or other bodily fluid contains. And if CRISPR detects the genetic markers of a pathogen, it can let researchers know by fluorescing. No glow means no virus.
This method would be fantastic for cheap, point-of-care initial testing, said Alexandra East-Seletsky, the lead author on the study in Molecular Cell and a post-doc in the Berkeley lab of Jennifer Doudna, one of the scientists who initially discovered CRISPR. The power of the system is flexibility and speed for targeting new sequences, making it ideal for use during an infectious disease outbreak, or other systems requiring fast development.
The work piggy backs off earlier work by both Berkeley and the Broad Institute. In September, Berkeley researchers reported the discovery of Cas13a and its ability to detected specific sequences of RNA. Last month, the Broad Institute reported that it had used Cas13a to develop a diagnostic tool that could detect Zika and other viruses. At the time, they said that their technique was not only small and portable, but could cost as little as 61 cents per test in the field. Such a tool might detect viral and bacterial diseases, as well as potentially cancer-causing mutations.
The new work essentially expands the tools available in the toolbox, allowing the CRISPR systems to detect more than one thing at once.
It allows you to test a control substrate and an unknown at the same time, or look for multiple disease-related sequences at once using the same starting material, said East-Seletsky. The possibilities are endless.
Developing cheap, bedside disease detection is a sort of Holy Grail of medicine. CRISPRs potential role here has received considerably less attention than its ability to edit genes, but it could wind up being equally significant.
Still, East-Seletsky said, Thursdays study is just a proof of concept. There is yet a lot of work to be done before there is actually a CRISPR-based diagnostic tool available to clinics.
See the original post here:
CRISPR Could Transform the Way We Diagnose Disease - Gizmodo
Scientists have eliminated HIV in mice using CRISPR – TechCrunch
TechCrunch | Scientists have eliminated HIV in mice using CRISPR TechCrunch An important breakthrough has been made in the eradication of AIDs. Scientists have found they can successfully snip out the HIV virus from mouse cells using CRISPR/Cas9 technology. Right now patients with the deadly virus must use a toxic concoction ... CRISPR and the Dawn of the New Biotech Revolution Researchers use gene editing to eliminate HIV infection in mice Closer to a cure: CRISPR cuts HIV from its cellular hideout |
Read more:
Scientists have eliminated HIV in mice using CRISPR - TechCrunch