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First human embryo editing experiment in U.S. ‘corrects’ gene for heart condition

By Ariana Eunjung Cha August 2 at 1:00 PM


Illustration of a human embryo. (iStock)

Scientists have successfully edited the DNA of human embryos to erase a heritable heart condition, cracking open the doors to a controversial new era in medicine.

This is the first time gene editing on human embryos has been conducted in the United States. Researchers said in interviews this week that they consider their work very basic. The embryos were allowed to grow for only a few days, and there was never any intention to implant them to create a pregnancy. But they also acknowledged that they will continue to move forward with the science, with the ultimate goal of being able to “correct” disease-causing genes in embryos that will develop into babies.

News of the remarkable experiment began to circulate last week, but details became public Wednesday with a paper in the journal Nature.

The experiment is the latest example of how the laboratory tool known as CRISPR (or Clustered Regularly Interspaced Short Palindromic Repeats), a type of “molecular scissors,” is pushing the boundaries of our ability to manipulate life, and it has been received with both excitement and horror.

The most recent work is particularly sensitive because it involves changes to the germ line — that is, genes that could be passed on to future generations. The United States forbids the use of federal funds for embryo research, and the Food and Drug Administration is prohibited from considering any clinical trials involving genetic modifications that can be inherited. A report from the National Academies of Sciences, Engineering and Medicine in February urged caution in applying CRISPR to human germ-line editing but laid out conditions by which research should continue. The new study abides by those recommendations.

This animation depicts the CRISPR-Cas9 method for genome editing – a powerful new technology with many applications in biomedical research, including the potential to treat human genetic disease or provide cosmetic enhancements. (Feng Zhang/McGovern Institute for Brain Research/MIT)

Shoukhrat Mitalipov, one of the lead authors of the paper and a researcher at Oregon Health & Science University, said that he is conscious of the need for a larger ethical and legal discussion about genetic modification of humans but that his team's work is justified because it involves “correcting” genes rather than changing them.

“Really we didn’t edit anything. Neither did we modify anything,” Mitalipov said. “. . . Our program is toward correcting mutant genes.”

Alta Charo, a bioethicist at the University of Wisconsin at Madison who is co-chair of the National Academies committee looking at gene editing, said that concerns about the work that have been circulating in recent days are overblown.

“What this represents is a fascinating, important and rather impressive incremental step toward learning how to edit embryos safely and precisely,” she said. However, “no matter what anybody says, this is not the dawn of the era of the designer baby.” She said that characteristics such as intelligence are influenced by multiple genes and that researchers don't understand all the components of how such characteristics are inherited, much less have the ability to redesign them.

The research involved eggs from 12 healthy female donors and sperm from a male volunteer who carries the MYBPC3 gene, which causes hypertrophic cardiomyopathy. HCM is a disease of the heart muscles that can cause no symptoms and remain undetected until it causes sudden cardiac death. There's no way to prevent or cure it, and it affects 1 in 500 people worldwide.

Around the time the sperm was injected into the eggs, researchers snipped out the gene that causes the disease. The result was far more successful than the researchers expected: As the embryo's cells began to divide and multiply, a huge number appeared to be repairing themselves by using the normal, non-mutated copy of the gene from the women's genetic material. In all, they saw that about 72 percent were corrected, a very high number. Researchers also noticed that there didn't seem to be any “off-target” changes in the DNA, which has been a major safety concern of gene-editing research.

Mitalipov said he hoped the technique could one day be applied to a wide variety of genetic diseases — more than 10,000 known disorders can be traced to a single gene — and that one of the team's next targets may be BRCA, which is associated with breast cancer.

The first published work involving human embryos, reported in 2015, was done in China and targeted a gene that leads to the blood disorder beta thalassemia. But those embryos were abnormal and nonviable, and there were far fewer than the number used in the U.S. study.

Juan Carlos Izpisua Belmonte, a researcher at the Salk Institute who is also a co-author on the new study, said that there are many advantages to treating an embryo rather than a child or an adult. When dealing with an embryo in its earliest stages, only a few cells are involved, while in a more mature human being there are trillions of cells in the body and potentially millions that must be corrected to eradicate traces of a disease.

Izpisua Belmonte said that even if the technology is perfected, it could deal with only a small subset of human diseases.

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“I don’t want to be negative with our own discoveries, but it is important to inform the public of what this means,” he said. “In my opinion the percentage of people that would benefit from this at the current way the world is is rather small.” For the process to make a difference, the child would have to be born through in vitro fertilization and the parents would have to know the child has the gene for a disease to get it changed. But the vast majority of children are conceived the natural way, and this correction technology would not work in utero.

For years, some policymakers, historians and scientists have been calling for a voluntary moratorium on the modification of the DNA of human reproductive cells. The most prominent expression of concern came in the form of a 2015 letter signed by Jennifer Doudna, the co-inventor of CRISPR-Cas9, Nobel laureate David Baltimore and 16 other prominent scientists. They warned that eliminating a genetic disease could have unintended consequences — on human genetics, society and even the environment — far into the future.

Mitalipov said he hopes regulators will provide more guidance on what should or should not be allowed.

Otherwise, he said, “this technology will be shifted to unregulated areas, which shouldn’t be happening.”

US Scientists prove cryogenically frozen life can be revived

Wednesday, 2 August 2017 by System Administrator

Canstockphoto3011993

US scientists prove cryogenically frozen life can be revived

Jamie Seidel, News Corp Australia Network

August 1, 2017 7:58pm

WANT to live forever? Or simply travel to a far future time? The chances of doing so just got a step closer, with a breakthrough in cryogenic freezing.

The most obvious use is space travel.

Space is big. And getting anywhere takes lots of time, not to mention resources.

So sending crews into a deep sleep makes sense.

If it can be made to work. And safe.

The idea is to preserve bodies and brains in a state of suspended animation.

Science has managed to do this for individual cells.

Reviving a living organism has proven to be a much more challenging matter.

Until now.

The science journal ACS Nano has published an article where US researchers report successfully thawing — and reanimating — frozen zebra fish embryos.

It’s significant because 60 years worth of similar attempts have failed.

The core of the issue are ice crystals.

Frozen water expands. As a result, ice will burst a cell from the inside out.

Replacing part of a body’s fluids with antifreeze has long been thought of as a possible solution.

Antifreeze filled zebrafish embryos — chosen because they are largely translucent and easy to study — have been snap-frozen to -196C in liquid nitrogen now for decades.

The problem has defrosting them.

How to cryopreserve fish embryos and bring them back to life

“The large size of the yolk still impedes rapid cooling and warming, thereby yielding lethal ice crystal formation during cryopreservation,” the researchers write.

Even using a millisecond-long flash of warmth from a laser wasn’t raising their temperatures fast enough and evenly enough to avoid the emergence of ice crystals.

But the solution appears to be another additive to the original antifreeze: gold nano-rods.

These tiny fragments of metal conduct the laser’s heat.

This speeds up and distributes the laser’s warming process more evenly.

US researchers have successfully reanimated zebra fish embryos after 'deep freezing' them in a cryogenic suspension process. Source: ACS Nano

 The reality behind the dream of suspended animation

After being filled with the new antifreeze, and kept for a few minutes at -196C, they underwent the laser rapid-defrost treatment.

“This rapid warming process led to the outrunning of ice formation, which can damage the embryos,” the study says.

Some 10 per cent of the embryos survived, and began to grow — and move — once again.

It’s not great odds.

But it’s a very real start.

Originally published as Suspended animation a step closer

 

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New nuclear magnetic resonance technique offers ‘molecular window’ for live disease diagnosis

Could use existing non-invasive MRI technology

May 3, 2017

New nuclear magnetic resonance (NMR) system for molecular diagnosis (credit: University of Toronto Scarborough)

University of Toronto Scarborough researchers have developed a new “molecular window” technology based on nuclear magnetic resonance (NMR) that can look inside a living system to get a high-resolution profile of which specific molecules are present, and extract a full metabolic profile.

“Getting a sense of which molecules are in a tissue sample is important if you want to know if it’s cancerous, or if you want to know if certain environmental contaminants are harming cells inside the body,” says Professor Andre Simpson, who led research in developing the new technique.*

An NMR spectrometer generates a powerful magnetic field that causes atomic nuclei to absorb and re-emit energy in distinct patterns, revealing a unique molecular signature — in this example: the chemical ethanol. (credit: adapted from the Bruker BioSpin “How NMR Works” video at www.theresonance.com/nmr-know-how)

Simpson says there’s great medical potential for this new technique, since it can be adapted to work on existing magnetic resonance imaging (MRI) systems found in hospitals. “It could have implications for disease diagnosis and a deeper understanding of how important biological processes work,” by targeting specific biomarker molecules that are unique to specific diseased tissue.

The new approach could detect these signatures without resorting to surgery and could determine, for example, whether a growth is cancerous or benign directly from the MRI alone.

The technique could also provide highly detailed information on how the brain works, revealing the actual chemicals involved in a particular response. “It could mark an important step in unraveling the biochemistry of the brain,” says Simpson.

Overcoming magnetic distortion

Until now, traditional NMR techniques haven’t been able to provide high-resolution profiles of living organisms because of magnetic distortions from the tissue itself.  Simpson and his team were able to overcome this problem by creating tiny communication channels based on “long-range dipole interactions” between molecules.

The next step for the research is to test it on human tissue samples, says Simpson. Since the technique detects all cellular metabolites (substances such as glucose) equally, there’s also potential for non-targeted discovery.

“Since you can see metabolites in a sample that you weren’t able to see before, you can now identify molecules that may indicate there’s a problem,” he explains. “You can then determine whether you need further testing or surgery. So the potential for this technique is truly exciting.”

The research results are published in the journal Angewandte Chemie.

* Simpson has been working on perfecting the technique for more than three years with colleagues at Bruker BioSpin, a scientific instruments company that specializes in developing NMR technology. The technique, called “in-phase intermolecular single quantum coherence” (IP-iSQC), is based on some unexpected scientific concepts that were discovered in 1995, which at the time were described as impossible and “crazed” by many researchers. The technique developed by Simpson and his team builds upon these early discoveries. The work was supported by Mark Krembil of the Krembil Foundation and the Natural Sciences Engineering Research Council of Canada (NSERC).


Abstract of In-Phase Ultra High-Resolution In Vivo NMR

Although current NMR techniques allow organisms to be studied in vivo, magnetic susceptibility distortions, which arise from inhomogeneous distributions of chemical moieties, prevent the acquisition of high-resolution NMR spectra. Intermolecular single quantum coherence (iSQC) is a technique that breaks the sample’s spatial isotropy to form long range dipolar couplings, which can be exploited to extract chemical shift information free of perturbations. While this approach holds vast potential, present practical limitations include radiation damping, relaxation losses, and non-phase sensitive data. Herein, these drawbacks are addressed, and a new technique termed in-phase iSQC (IP-iSQC) is introduced. When applied to a living system, high-resolution NMR spectra, nearly identical to a buffer extract, are obtained. The ability to look inside an organism and extract a high-resolution metabolic profile is profound and should find applications in fields in which metabolism or in vivo processes are of interest.

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Topics: Biomed/Longevity | Cognitive Science/Neuroscience

 

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