Tag Archives: Gene-editing

Gold Nanoparticles Ship With Efficiency CRISPR Cargo

Forget UPS and FedEx: Tiny golden delivery trucks created at Fred Hutchinson Cancer Research Center can ship CRISPR into human blood stem cells, offering a potential way to treat diseases like HIV and sickle cell anemia. And the researchers behind those trucks have even bigger distribution dreams. Gene therapy — the editing of our DNA to treat disease — is a clinical reality today, but only in a handful of rich countries. Fred Hutch scientists think their new CRISPR courier could help deliver gene therapy to patients around the world.

A new paper published in Nature Materials describes how the scientists loaded CRISPR onto spherical gold nanoparticles. These tiny shuttles then deposited the gene-editing tool into blood stem cells donated by healthy individuals and isolated in test tubes, where CRISPR altered genes related to HIV and certain blood disorders.   It is the first time that nanoparticles have successfully ferried CRISPR into blood stem cells to edit DNA, the researchers said. And it’s a promising step toward addressing CRISPR’s critical delivery problems. The first of these problems has vexed the field since the gene-editing technique was discovered. Scientists need to deliver CRISPR into the right spot in a cell. That is proving tricky enough. DNA represents the body’s crown jewels, and CRISPR must sneak past all sorts of security systems to gain access.

And then CRISPR must go global. Gene editing could benefit millions of people worldwide. But as the treatment process stands right now, the vast majority won’t. That process depends almost entirely on highly engineered viruses made in high-tech, multimillion-dollar facilities.
The researchers think their golden nanoparticles can solve both problems. As efficient couriers, they could reduce the need for engineered viruses and specialized research centers. And that could help make these emerging, high-tech treatments accessible and affordable, said senior scientist Dr. Jennifer Adair of Fred Hutch.

Gene therapy has a lot of potential across many diseases, but the process we have right now is just not feasible in every place in the world,” Adair said. “We want to end up delivering gene therapy in a syringe. This gold nanoparticle represents the first possibility we have to do that for blood stem cells.”

Source: https://www.fredhutch.org/

Gene Editing To Make Cells Immune To HIV

Some viruses, no matter how hard we try, remain resistant to vaccines. Now, researchers are using a different method, gene editing, as a way to make cells immune to mankind’s most difficult viruses. Led by Dr. Justin Taylor, a team at the Fred Hutchinson Cancer Research Center has targeted four infections for which there’s no protective vaccine: HIV, influenza, the Epstein-Barr virus (EBV) and respiratory syncytial virus (RSV).

The researchers used CRISPR/Cas9 technology to modify B cells, a class of white blood cells that produce antibodies to protect us from diseases. By coding the cells with genes that create specific antibodies, the team was able to make them immune without the use of a vaccine.

The researchers tested the method in both human cells in a test tube and in living mice. On average, about 30 percent of the cells produced the desired antibody. Taylor said that the mice remained protected for 83 days following the procedure, an important benchmark given that patients who receive stem cell transplants can have weakened immune systems for three to six months. To be clear, Taylor doesn’t have anything against traditional vaccination. “Vaccines are great,” he said. “I wish we had more of them.”

Instead, Taylor thinks the gene editing method could work one day for diseases where we don’t have a vaccine. It may help patients who are immuno-compromised, meaning their bodies can no longer fight infections, as well as older patients whose bodies aren’t as receptive to vaccines. Gene-edited immunity might also be used to protect people faster than can be done with traditional vaccines, which could be useful during unexpected outbreaks.

Taylor’s team included Fred Hutch researchers and co-authors Howell Moffett, Carson Harms, Kristin Fitzpatrick, Marti Tooley and Jim Boonyaratanakornkit. The results will be published in the journal Science Immunology.

Source: https://www.fredhutch.org/
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https://www.geekwire.com/

Premature Aging, Obesity, Brain Disorders: 3 FrontRunners In The CRISP-R Therapy Race

CRISPR is the ultimate child star in the biomedical universe. Just six years old, the gene editing prodigy is now the subject of multiple clinical trials that aim to push the lab tech into the real world. In 2017, a 44-year-old man received the first-ever dose of gene therapy—in the form of zinc-finger nucleases—that targeted a deficient gene in his liver. This type of gene therapy, called “in vivo” in scientist-speak, is markedly different than the most common type these days.

So far, the only gene therapies on the market are CAR-Ts: a procedure targeting blood cancer that extracts a person’s immune cells, genetically edits them within the lab to boost their cancer-killing power, and then infuses them back into the body.

In vivo gene therapy is far more intimate: rather than extracting a person’s cells, a gene editing mix is directly injected into a person, with the hope of performing molecular surgery with a single shot. CRISPR is now making that possibility very real. With dozens of efforts in the making, from premature aging to obesity and developmental brain disorders, here are the frontrunners beyond CRISPR-based cancer therapy to watch out for.

Source: https://singularityhub.com/

How To Detect Genetic Mutations In Minutes

A team of engineers at the UC Berkeley and the Keck Graduate Institute (KGI) of The Claremont Colleges combined CRISPR with electronic transistors made from graphene to create a new hand-held device that can detect specific genetic mutations in a matter of minutes.

The device, dubbed CRISPR-Chip, could be used to rapidly diagnose genetic diseases or to evaluate the accuracy of gene-editing techniques. The team used the device to identify genetic mutations in DNA samples from Duchenne muscular dystrophy patients.

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We have developed the first transistor that uses CRISPR to search your genome for potential mutations,” said Kiana Aran, an assistant professor at KGI who conceived of the technology while a postdoctoral scholar in UC Berkeley bioengineering professor Irina Conboy’s lab. “You just put your purified DNA sample on the chip, allow CRISPR to do the search and the graphene transistor reports the result of this search in minutes.”

Aran, who developed this technology and brought it to fruition at KGI, is the senior author of a paper describing the device that appears online March 25 in the journal Nature Biomedical Engineering.

Doctors and geneticists can now sequence DNA to pinpoint genetic mutations underlying a host of traits and conditions, and companies like 23andMe and AncestryDNA even make these tests available to curious consumers.

Source: https://news.berkeley.edu/

Have China’s CRISPR Twins Enhanced Brains?

New research suggests that a controversial gene-editing experiment to make children resistant to HIV may also have enhanced their ability to learn and form memories. The twins, called Lulu and Nana, reportedly had their genes modified before birth by a Chinese scientific team using the new editing tool CRISPR. The goal was to make the girls immune to infection by HIV, the virus that causes AIDS. Now, new research shows that the same alteration introduced into the girls’ DNA, deletion of a gene called CCR5, not only makes mice smarter but also improves human brain recovery after stroke, and could be linked to greater success in school.

The answer is likely yes, it did affect their brains,” says Alcino J. Silva, a neurobiologist at the University of California, Los Angeles, whose lab uncovered a major new role for the CCR5 gene in memory and the brain’s ability to form new connections.

“The simplest interpretation is that those mutations will probably have an impact on cognitive function in the twins,” says Silva. He says the exact effect on the girls’ cognition is impossible to predict, and “that is why it should not be done.”

The Chinese team, led by He Jiankui of the Southern University of Science and Technology in Shenzhen, claimed it used CRISPR to delete CCR5 from human embryos, some of which were later used to create pregnanciesHIV requires the CCR5 gene to enter human blood cells.

The experiment has been widely condemned as irresponsible, and He is under investigation in China. News of the first gene-edited babies also inflamed speculation about whether CRISPR technology could one day be used to create super-intelligent humans, perhaps as part of a biotechnology race between the US and China.

There is no evidence that He actually set out to modify the twins’ intelligence. MIT Technology Review contacted scientists studying the effects of CCR5 on cognition, and they say the Chinese scientist never reached out to them, as he did to others from whom he hoped to get scientific advice or support.
As far as I know, we never heard from him,” says Miou Zhou, a professor at the Western University of Health Sciences in California.

Although He never consulted the brain researchers, the Chinese scientist was certainly aware of the link between CCR5 and cognition.  It was first shown in 2016 by Zhou and Silva, who found that removing the gene from mice significantly improved their memory. The team had looked at more than 140 different genetic alterations to find which made mice smarter.

Source: https://www.technologyreview.com/

Sharpen Molecular Scissors And Expand The Gene Editing Toolbox

Wake Forest Institute for Regenerative Medicine (WFIRM) scientists have figured out a better way to deliver a DNA editing tool to shorten the presence of the editor proteins in the cells in what they describe as a “hit and run” approach.

CRISPR (clustered regularly interspaced short palindromic repeats) technology is used to alter DNA sequences and modify gene function. CRISPR/Cas9 is an enzyme that is used like a pair of scissors to cut two strands of DNA at a specific location to add, remove or repair bits of DNA. But CRISPR/Cas9 is not 100 percent accurate and could potentially cut unexpected locations, causing unwanted results.

One of the major challenges of CRISPR/Cas9 mRNA technologies is the possibility of off-targets which may cause tumors or mutations,” said Baisong Lu, Ph.D, assistant professor of regenerative medicine at WFIRM and one of the lead authors of the paper. Although other types of lentivirus-like bionanoparticles (LVLPs) have been described for delivering proteins or mRNAs, Lu said, “the LVLP we developed has unique features which will make it a useful tool in the expanding genome editing toolbox.

To address the inaccuracy issue, WFIRM researchers asked the question: Is there a way to efficiently deliver Cas9 activity but achieve transient expression of genome editing proteins? They tested various strategies and then took the best properties of two widely used delivery vehicles – lentivirus vector and nanoparticles – and combined them, creating a system that efficiently packages Cas9 mRNA into LVLPs, enabling transient expression and highly efficient editing.

Lentiviral vector is a widely used gene delivery vehicle in research labs and is already widely used for delivering the CRISPR/Cas9 mRNA technology for efficient genome editing. Nanoparticles are also being used but they are not as efficient in delivery of CRISPR/Cas9.

By combining the transient expression feature of nanoparticle-delivery strategies while retaining the transduction efficiency of lentiviral vectors, we have created a system that may be used for packaging various editor protein mRNA for genome editing in a ‘hit and run’ manner,” said Anthony Atala, M.D., director of WFIRM and co-lead author of the paper. “This system will not only improve safety but also avoid possible immune response to the editor proteins, which could improve in vivo gene editing efficiency which will be useful in research and clinical applications.

The WFIRM team published its findings in a paper published recently in the journal  Nucleic Acids Research.

Source: https://school.wakehealth.edu/

 

How To Fine-Tune the Gene Scissors CRISPR

When researchers and doctors use the tool CRISPR to correct genetic errors, it may have side effects on the human genome. Now, researchers from the University of Copenhagen have learned how the molecular machinery behind CRISPR works and thus expect to be able to fine-tune CRISPR and remove the undesired effects.

The introduction of the tool for gene editing, the so-called gene scissors CRISPR, in 2007 was a revolution within medical science and cell biology. But even though the perspectives are great, the launch of CRISPR has been followed by debate, especially focussing on ethical issues and the technology’s degree of accuracy and side effects.

However, in a new study published in the scientific journal Cell researchers from the Novo Nordisk Foundation Center for Protein Research have described how one of the CRISPR technologies, the so-called Cas12a, works – all the way down to the molecular level. This makes it possible to fine-tune the gene-editing process to only achieve the desired effects.

If we compare CRISPR to a car engine, what we have done is make a complete 3D map of the engine and thus gained an understanding of how it works. This knowledge will enable us to fine-tune the CRISPR engine and make it work in various ways – as a Formula 1 racer as well as an off-road truck’, says Professor Guillermo Montoya from the Novo Nordisk Foundation Center for Protein Research.

The researchers have used a so-called cryo-electron microscope to map the technology. The recently inaugurated cryoEM facility at the University of Copenhagen has established the state-of-the-art technology enabling the researchers to take photographs of the different shapes of the molecule when CRISPR-Cas12a cuts up the DNA strand.

According to the researchers, their new findings can explain why CRISPR technology can have side effects on the genome. Once the DNA strand has been cut, the three ‘security checks’ remain open. This can cause the process to last longer than wanted, because the machinery behind gene editing continues to run and can cause genetic changes. However, now the researchers expect their new knowledge to put an end to this. They believe it can be used to fine-tune the gene-editing technology right away.

Source: https://healthsciences.ku.dk/

Gene-editing Tools Will Alter Foods Precisely And Cheaply

The next generation of biotech food is headed for the grocery aisles, and first up may be salad dressings or granola bars made with soybean oil genetically tweaked to be good for your heart. By early next year, the first foods from plants or animals that had their DNAedited” are expected to begin selling. It’s a different technology than today’s controversial “genetically modifiedfoods, more like faster breeding that promises to boost nutrition, spur crop growth, and make farm animals hardier and fruits and vegetables last longer.

The U.S. National Academy of Sciences has declared gene editing one of the breakthroughs needed to improve food production so the world can feed billions more people amid a changing climate. Yet governments are wrestling with how to regulate this powerful new tool. And after years of confusion and rancor, will shoppers accept gene-edited foods or view them as GMOs in disguise?

GMOs, or genetically modified organisms, are plants or animals that were mixed with another species’ DNA to introduce a specific trait — meaning they’re “transgenic.” Best known are corn and soybeans mixed with bacterial genes for built-in resistance to pests or weed killers.

If the consumer sees the benefit, I think they’ll embrace the products and worry less about the technology,” said Dan Voytas, a University of Minnesota professor and chief science officer for Calyxt Inc., which edited soybeans to make the oil heart-healthy.

Researchers are pursuing more ambitious changes: Wheat with triple the usual fiber, or that’s low in gluten. Mushrooms that don’t brown, and better-producing tomatoes. Drought-tolerant corn, and rice that no longer absorbs soil pollution as it grows. Dairy cows that don’t need to undergo painful de-horning, and pigs immune to a dangerous virus that can sweep through herds.

Scientists even hope gene editing eventually could save species from being wiped out by devastating diseases like citrus greening, a so far unstoppable infection that’s destroying Florida’s famed oranges. First they must find genes that could make a new generation of trees immune.

If we can go in and edit the gene, change the DNA sequence ever so slightly by one or two letters, potentially we’d have a way to defeat this disease,” said Fred Gmitter, a geneticist at the University of Florida Citrus Research and Education Center, as he examined diseased trees in a grove near Fort Meade.

Source: https://whyy.org/

CRISPR-SKIP, New Gene Editing Technique

What if doctors could treat previously incurable genetic diseases caused by errors or mutations in genes? Thanks to new research by American scientists at the University of Illinois, we are one step closer to making that a reality. Published in Genome Biology, their work is based on CRISPR-Cas9, a groundbreaking genome editing system.

Typically, cells in the body “readDNA to produce the proteins needed for different biological functions. . Scientists can change how the DNA is read using CRISPR gene-editing technology. CRISPR-Cas9 is often used to cut out specific areas of DNA and repair faulty genes. In the current study, the researchers modified existing technology to create CRISPR-SKIP. Instead of breaking DNA to cut faulty genes out, CRISPR-SKIP changes a single base of the targeted DNA sequence, causing the cell to skip reading that section of DNA.

According to the study authors, CRISPR-SKIP can eliminate faulty sections of DNA permanently, allowing for long-lasting treatment of some genetic diseases with one treatment. They successfully tested their technique in cell lines from both mice and humans. The scientists aim to test the method in live organisms in the future.

CRISPR-SKIP has the potential to help treat many diseases such as cancer, rheumatoid arthritis, Huntington’s disease, and Duchenne muscular dystrophy to name a few. Because the method only requires editing of a single base, it is simple, precise, and adaptable to a variety of cell types and applications.

Source: https://news.illinois.edu/
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https://www.medicalnewsbulletin.com/

CRISPR Reverses Duchenne Muscular Dystrophy Mutation

CRISPR-Cas9 has, for the first time, been tested by systemic delivery in a large animal—and the results are striking. Working in a dog model of Duchenne muscular dystrophy (DMD), the gene editing not only restored the expression of the protein dystrophin, it also improved muscle histology in the dogs.

Our technology was developed using human cells and mice to correct the same type of mutation as in these dogs. It was critical for us to test gene editing in a large animal because it harbors a mutation analogous to the most common mutation in DMD patients,” said Eric Olson, Ph.D., professor and chair of molecular biology at the University of Texas Southwestern Medical Center and lead author. The researchers wrote that this is “an essential step toward clinical translation of gene editing as a therapeutic strategy for DMD.”

Indeed, Dame Kay E. Davies, Ph.D., professor of anatomy and director of the MRC Functional Genomics Unit at the University of Oxford and a pioneer in the field of DMD research, echoes this sentiment explains, “This is a very exciting paper as it shows that gene editing can be reasonably affective in a large animal model of DMD.”

The paper, “Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy,” appears in the last issue of Science.

Source: https://www.genengnews.com/