New Genetic And Stem-Cell Technology To Grow Sheets Of Skin

Somewhere in Germany’s Ruhr valley, a nine-year-old boy is doing what children do: playing football, joking around with friends and going to school. Two years ago, he was confined to a hospital bed, dying of a rare and cruel genetic skin disease. The boy had junctional epidermolysis bullosa, or JEB. He, like other people with the disease, carried a mutation in a gene that controls the integrity of the skin. Doctors could only try to ease his suffering as some 80% of his skin simply fell away.

A team of Italian researchers came to his aid by combining stem-cell techniques with gene therapy. As a young scientist at Harvard Medical School in Boston, Massachusetts, in the 1980s, Michele De Luca — the lead author of the new study — watched pioneers in skin regeneration learn to grow small sheets of skin from cells taken from burns patients, and to use them in grafts. He extended the work in Italy, applying new genetic and stem-cell technologies. He developed ways to generate stem cells from human skin, replace disease-causing genes in them and grow sheets of healthy skin on scaffolds in the lab.

He chose JEB for his first clinical trial, which he registered with the Italian Medicines Agency in 2002. Four years later, he reported his first success, in which he created healthy skin patches from biopsies to replace small areas of sloughed-off skin on the legs of a patient with a form of JEB (F. Mavilio et al. Nature Med. 12, 1397–1402; 2006). New European Commission regulations introduced in 2007 required him to pause the project while he created facilities adhering to ‘good manufacturing practices’ (GMPs) and a spin-off company to meet the demands for strengthened oversight of cell-based therapies.

Having a company refocused his team’s attention on a different type of stem-cell therapy, one likely to yield a product for the market faster. Holoclar, a treatment that replaces the eye’s cornea in a form of blindness, became the world’s first commercial stem-cell therapy in 2015.

A few months later, at the University of Modena, De Luca got a call out of the blue from doctors in Germany who were trying to treat the little boy. Because the therapy had been in a clinical trial, albeit one on hold at the time, and because De Luca could provide GMP services, German regulatory authorities quickly approved the one-off compassionate use of the JEB therapy. Surgeons in Germany sent a skin biopsy to Modena, and two major skin transplants followed. Six months after the initial biopsy, the boy returned to school. During the many months since, he has not had so much as a blister, and loves to show off his ‘new skin’. By their nature, highly personalized treatments using gene therapies and products derived from an individual’s stem cells are likely to be applicable to only a subset of patients.

Scientists and clinicians have presented the details of the recovery in Nature (T. Hirsch et al.Nature http://dx.doi.org/10.1038/nature24487; 2017). This major clinical development was based on decades of basic research. The clinical data gathered during 21 months of follow-up after the boy’s treatment have also led to major insights into human skin biology, as discussed in an accompanying News & Views (M. Aragona and C. Blanpain Naturehttp://dx.doi.org/10.1038/nature24753; 2017). For example, normal regeneration of the epidermis is directed by only a few stem-cell clones that can self-renew.

Source: http://www.nature.com/

Editing Genes In Human Embryos

Two new CRISPR tools overcome the scariest parts of gene editing.The ability to edit RNA and individual DNA base pairs will make gene editing much more precise. Several years ago, scientists discovered a technique known as CRISPR/Cas9, which allowed them to edit DNA more efficiently than ever before.
Since then, CRISPR science has exploded; it’s become one of the most exciting and fast-moving areas of research, transforming everything from medicine to agriculture and energy. In 2017 alone, more than 14,000 CRISPR studies were published.

But here’s the thing: CRISPR, while a major leap forward in gene editing, can still be a blunt instrument. There have been problems with CRISPR modifying unintended gene targets and making worrisome, and permanent, edits to an organism’s genome. These changes could be passed down through generations, which has raised the stakes of CRISPR experiments — and the twin specters of “designer babies” and genetic performance enhancers — particularly when it comes to editing genes in human embryos.
So while CRISPR science is advancing quickly, scientists are still very much in the throes of tweaking and refining their toolkit. And on Wednesday, researchers at the Broad Institute of MIT and Harvard launched a coordinated blitz with two big reports that move CRISPR in that safer and more precise direction.
In a paper published in Science, researchers described an entirely new CRISPR-based gene editing tool that targets RNA, DNA’s sister, allowing for transient changes to genetic material. In Nature, scientists described how a more refined type of CRISPR gene editing can alter a single bit of DNA without cutting it — increasing the tool’s precision and efficiency.

The first paper, out Wednesday in Science, describes a new gene editing system. This one, from researchers at MIT and Harvard, focuses on tweaking human RNA instead of DNA.

Our cells contain chromosomes made up of chemical strands called DNA, which carry genetic information. Those genes have recipes for proteins that lead to a bunch of different traits. But to carry out the instructions in any one recipe, DNA needs another type of genetic material called RNA to get involved.

RNA is ephemeral: It acts like a middleman, or a messenger. For a gene to become a protein, that gene has to be transcribed into RNA in the cell, and the RNA is then read to make the protein. If the DNA is permanent — the family recipe book passed down through generations — the RNA is like your aunt’s scribbled-out recipe on a Post-It note, turning up only when it’s needed and disappearing again.

With the CRISPR/Cas9 system, researchers are focused on editing DNA. (For more on how that system works, read this Vox explainer.) But the new Science paper describes a novel gene editing tool called REPAIR that’s focused on using a different enzyme, Cas13, to edit that transient genetic material, the RNA, in cells. REPAIR can target specific RNA letters, or nucleosides, that are involved in single-base changes that regularly cause disease in humans.

This is hugely appealing for one big reason: With CRISPR/Cas9, the changes to the genome, or the cell’s recipe book, are permanent. You can’t undo them. With REPAIR, since researchers can target single bits of ephemeral RNA, the changes they make are transient, even reversible. So this system could fix genetic mutations without actually touching the genome (like throwing away your aunt’s Post-It note recipe without adding it to the family recipe book).

Source: https://www.vox.com/

Gene Researchers Have Created Green Mice

These are no Frankenstein mice. Their green feet come courtesy of a fluorescent green jelly fish gene added to their own genome. This allows a team of British scientists to test out gene editing using CRISPR-Cas9 technology.

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“We take what were or would have been green embryos and we make them into non-green embryos, so it’s a really great way of demonstrating the method“, said Dr. Anthony Perry, reproductive biologist at the University of Bath.

The technique uses the ribonucleic acid molecule CRISPR together with the Cas9 protein enzyme. CRISPR guides the Cas9 protein to a defective part of a genome where it acts like molecular scissors to cut out a specific part of the DNA. This could revolutionise how we treat diseases with a genetic component, like sickle cell anaemia. The technique is being pioneered in the U.S.
We now have a technology that allows correction of a sequence that would lead to normally functioning cells. And I think you know the opportunities with this are really exciting and really profound. There are many diseases that are have known genetic causes that we now have in principle a way to cure,“explains Jennifer Doudna, Professor of cell biology at the University of Berkeley.
Last year two teams of U.S. based scientists used CRISPR-Cas9 technology in mice to correct the genetic mutation that causes sickle cell disease. Although researchers aren’t yet close to using CRISPR-Cas9 to edit human embryos for implantation into the womb – some are already warning against it.

Dr David King, Director of  Human Genetics Alert, comments: “It will immediately create this new form of what we call consumer eugenics, that’s to say eugenics driven by the free market and consumer preferences in which people choose the cosmetic characteristics and the abilities of their children and try to basically enhance their children to perform better than other people’s children.” Other potential applications of the technology could be to make food crops and livestock animal species disease-resistant. The British team say CRISPR-Cas9 presents a golden opportunity to prevent genetic disease.

Source: http://www.reuters.com/
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Faulty DNA Linked To Fatal Heart Condition Removed From Embryo

Scientists have modified human embryos to remove genetic mutations that cause heart failure in otherwise healthy young people in a landmark demonstration of the controversial procedure. It is the first time that human embryos have had their genomes edited outside China, where researchers have performed a handful of small studies to see whether the approach could prevent inherited diseases from being passed on from one generation to the next.

While none of the research so far has created babies from modified embryos, a move that would be illegal in many countries, the work represents a milestone in scientists’ efforts to master the technique and brings the prospect of human clinical trials one step closer. The work focused on an inherited form of heart disease, but scientists believe the same approach could work for other conditions caused by single gene mutations, such as cystic fibrosis and certain kinds of breast cancer.

This embryo gene correction method, if proven safe, can potentially be used to prevent transmission of genetic disease to future generations,” said Paula Amato, a fertility specialist involved in the US-Korean study at Oregon Health and Science University.

The scientists used a powerful gene editing tool called Crispr-Cas9 to fix mutations in embryos made with the sperm of a man who inherited a heart condition known as hypertrophic cardiomyopathy, or HCM. The disease, which leads to a thickening of the heart’s muscular wall, affects one in 500 people and is a common cause of sudden cardiac arrest in young people. Humans have two copies of every gene, but some diseases are caused by a mutation in only one of the copies. For the study, the scientists recruited a man who carried a single mutant copy of a gene called MYBPC3 which causes HCM.

Source: https://www.theguardian.com/

Cancer: A Giant Step For Immunotherapy

A Food and Drug Administration (FDA) panel opened a new era in medicine, unanimously recommending that the agency approve the first-ever treatment that genetically alters a patient’s own cells to fight cancer, transforming them into what scientists call “a living drug” that powerfully bolsters the immune system to shut down the disease.

If the F.D.A. accepts the recommendation, which is likely, the treatment will be the first gene therapy ever to reach the market. Others are expected: Researchers and drug companies have been engaged in intense competition for decades to reach this milestone. Novartis is now poised to be the first. Its treatment is for a type of leukemia, and it is working on similar types of treatments in hundreds of patients for another form of the disease, as well as multiple myeloma and an aggressive brain tumor.

To use the technique, a separate treatment must be created for each patient — their cells removed at an approved medical center, frozen, shipped to a Novartis plant for thawing and processing, frozen again and shipped back to the treatment center.

A single dose of the resulting product has brought long remissions, and possibly cures, to scores of patients in studies who were facing death because every other treatment had failed. The panel recommended approving the treatment for B-cell acute lymphoblastic leukemia that has resisted treatment, or relapsed, in children and young adults aged 3 to 25.

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We believe that when this treatment is approved it will save thousands of children’s lives around the world,” Emily’s father, Tom Whitehead, told the panel. “I hope that someday all of you on the advisory committee can tell your families for generations that you were part of the process that ended the use of toxic treatments like chemotherapy and radiation as standard treatment, and turned blood cancers into a treatable disease that even after relapse most people survive.”

The main evidence that Novartis presented to the F.D.A. came from a study of 63 patients who received the treatment from April 2015 to August 2016. Fifty-two of them, or 82.5 percent, went into remission — a high rate for such a severe disease. Eleven others died.

It’s a new world, an exciting therapy,” said Dr. Gwen Nichols, the chief medical officer of the Leukemia and Lymphoma Society, which paid for some of the research that led to the treatment. The next step, she said, will be to determine “what we can combine it with and is there a way to use it in the future to treat patients with less disease, so that the immune system is in better shape and really able to fight.” She added, “This is the beginning of something big.”

Source: http://www.chop.edu/
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Car Pollution: Nanoparticles Travel Directly From The Nose To The Brain

The closer a person lives to a source of pollution, like a traffic dense highway, the more likely they are to develop Alzheimer’s or dementia, according to a study by the University of Southern California (USC) that has linked a close connection to pollution and the diseases. In a mobile lab, located just off of one of Los Angeles’ busiest freeways, USC scientists used a state-of-the-art pollution particle collector capable of gathering nano-sized particulate matter.

car pollution

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We have shown that, as you would expect, the closer you get to the sources of these particles in our case the freeways, the higher the concentrations. So there is an exponential decay with distance. That means basically that, the concentration of where we are right now and if we were, let’s just say 20 or 10 or 50 yards from the freeway, those levels would be probably 10 times higher than where we are right now,” says Costas Sioutas, USC Professor of Environmental Engineering.

That means proximity to high concentrations of fossil fuel pollution, like a congested freeway, could be hazardous. Particulate matter roughly 30 times thinner than the width of a human hair, called PM2.5, is inhaled and can travel directly through the nose into the brain. Once there, the particles cause inflammatory responses and can result in the buildup of a type of plaque, which is thought to further the progression of Alzheimer’s. “Our study brought in this new evidence and I would say probably so far the most convincing evidence that the particle may increase the risk of dementia. This is really a public health problem. And I think the policy makers need to be aware of that, the public health risk associated with high level of PM2.5,” explains Jiu-Chiuan Chen, Associate Professor of Preventive Medicine.

USC researchers analyzed the data of more than 3,500 women who had the APOE4 gene, the major known risk-factor gene for Alzheimer’s disease. It showed that, over the course of a decade, the women who lived in a location with high levels of the PM2.5 pollution were 92 percent more likely to develop dementia.

Source: https://news.usc.edu/
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Personality prediction: ‘Person of Interest’ TV Show Becomes Real

Is Faception an ingenious way to increase public safety or an incursion into our civil liberties? The former, say its makers. The Israeli start-up says it can isolate human character traits in faces captured by photograph or video. It says it can distinguish about 20 different personality groups, ranging from champion poker players to crime suspects.

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What we do, we know, with high level of accuracy, your personality ingredients, behaviour, potential and so we can have a profile about someone, as an individual and the same we can do about a crowd…let’s say gate number eight there are too much people that potentially can be terrorists or violent audience so this is something that is very crucial for public safety“, says Shai Gilboa, CEO of Faception company.
Faception won’t say how the algorithm works, except that it somehow gleans genetic information that lies within facial expressions. The firm insists it has no interest in retaining collected data and that the system disregards racial profiling.

Security experts are not convinced that’s enough. “Certainly advancement in technologies that enable to monitor an individual and actually to assess certain traits or certain attributes about individuals in the open space opens surveillance and monitoring capabilities which kind of like put in risk private freedoms that we used to enjoy, like the freedom of privacy, like the freedom of communication that we used to enjoy and now the technoligy certainly changes the balance“, comments Dr. Nimrod Kozlovski, security expert. Counter-terror experts say the firm must improve its 86 percent successful detection rate for it to be useful in airports. Civil liberties campaigners might say it shouldn’t be used at all.

Source: http://www.faception.com/

The Gene That Causes Grey Hair Is Now Identified

No matter who you are; for most of us grey hair is an inevitable part of getting older. But what if you could switch off the gene that causes it? For the first time, scientists have identified a gene called IRF4 as the culprit behind grey hair. DNA samples from over 6,000 volunteers were collected in Latin America; chosen for the diverse ancestry of its inhabitants. And it turns out if you have your roots in Europe, grey hair is much more likely.

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This genetic variant of IRF4 has two forms; one form is present world-wide and the other form is present only in Europeans. And we saw that this particular European specific form gives you almost double the chance of hair greying,” says Dr Kaustubh Adhikari from University College London (UCL), department of cell and developmental biology.

The gene IRF4 helps regulate melanin in the body, which determines – among other things – hair colour. Age and environmental factors will, of course, influence how quickly IRF4 triggers hair greying. But the researchers say their discovery could lead to a treatment that could stop it in its tracks.

Switching off a gene is of course feasible, the issue is whether it will have the desired effect and whether it’s the right thing to do… But in terms of trying to develop a therapy to delay or prevent hair greying, that is something that is potentially feasible; yes“, comments Professor Andres Ruiz-Linares, UCL (department of BioSciences).

Scientists think that a simple cosmetic treatment for switching off the grey gene would take many more years of research. But for those keen to banish the grey forever, your prayers might one day be answered.

The study has been published in the journal  Nature Communications.

Source: https://www.ucl.ac.uk/

Nanodiamonds For Breast Cancer Treatment

UCLA researchers led by Professor Dean Ho from the Jane and Jerry Weintraub Center for Reconstructive Biotechnology, have developed a potentially more effective treatment for breast cancer. Doctors have begun to categorize breast cancers into four main groups according to the genetic makeup of the cancer cells. Which category a cancer falls into generally determines the best method of treatment. But cancers in one of the four groups — called “basal-like” or “triple-negative” breast cancer (TNBC) — have been particularly tricky to treat because they usually don’t respond to the “receptor-targeted” treatments that are often effective in treating other types of breast cancer. TNBC tends to be more aggressive than the other types and more likely to recur, and can also have a higher mortality rate. Using nanodiamonds between 4 and 6 nanometers in diameter and shaped like tiny soccer balls, the researchers form clusters following drug binding that have the ability to precisely deliver cancer drugs to tumors, significantly improving the drugs’ desired effect. In the UCLA study, the nanodiamond delivery system has been able to home in on tumor masses in mice with triple negative breast cancer.

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This study demonstrates the versatility of the nanodiamond as a targeted drug-delivery agent to a tumor site,” said Ho, who is also a member of the California NanoSystems Institute at UCLA, UCLA’s Jonsson Comprehensive Cancer Center and the UCLA Department of Bioengineering. “The agent we’ve developed reduces the toxic side effects that are associated with treatment and mediates significant reductions in tumor size.”
Findings from the study are published online April 15 in the peer-reviewed journal Advanced Materials.
Source: http://newsroom.ucla.edu/