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CRISPR-Cas9: Developments in Genomic Editing

Started by Recusant, November 28, 2015, 05:00:48 AM

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Recusant

Moving along (autoplay video at link, though the video seems decent enough).

"CRISPR Gene Editing Fixes Muscular Dystrophy in Dogs. Are Humans Next?" | TIME

QuoteThe powerful gene editing technology CRISPR is one small step closer to treating a human disease.

In a new paper published in Science, researchers led by Eric Olson, professor and chair of molecular biology at UT Southwestern Medical Center, reported that he and his team successfully used CRISPR to correct the genetic defect responsible for Duchenne muscular dystrophy in four beagles bred with the disease-causing gene. It's the first use of CRISPR to treat muscular dystrophy in a large animal. (Previous studies had tested the technology on rodents.) In varying degrees, the genetic therapy halted the muscle degradation associated with the disease.

[Continues . . .]
"Religion is fundamentally opposed to everything I hold in veneration — courage, clear thinking, honesty, fairness, and above all, love of the truth."
— H. L. Mencken


Dave

Tomorrow is precious, don't ruin it by fouling up today.
Passed Monday 10th Dec 2018 age 74

No one

Can the shit brained asshat element be removed from the DNA?

Recusant

I failed to note this story here when it first developed. Anyway, more information has come out and, well, it's not great.

"The CRISPR Baby Scandal Gets Worse by the Day" | The Atlantic

QuoteBefore last week, few people had heard the name He Jiankui. But on November 25, the young Chinese researcher became the center of a global firestorm when it emerged that he had allegedly made the first crispr-edited babies, twin girls named Lulu and Nana. Antonio Regalado broke the story for MIT Technology Review, and He himself described the experiment at an international gene-editing summit in Hong Kong. After his talk, He revealed that another early pregnancy is under way.

It is still unclear if He did what he claims to have done. Nonetheless, the reaction was swift and negative. The CRISPR pioneer Jennifer Doudna says she was "horrified," NIH Director Francis Collins said the experiment was "profoundly disturbing," and even Julian Savulescu, an ethicist who has described gene-editing research as "a moral necessity," described He's work as "monstrous."

Such a strong reaction is understandable, given the many puzzling and worrying details about the experiment. Even without any speculation about designer babies and Gattaca-like futures that may or may not come to pass, the details about what has already transpired are galling enough. If you wanted to create the worst possible scenario for introducing the first gene-edited babies into the world, it is difficult to imagine how you could improve on this 15-part farce.

[Continues . . .]
"Religion is fundamentally opposed to everything I hold in veneration — courage, clear thinking, honesty, fairness, and above all, love of the truth."
— H. L. Mencken


Tank

If religions were TV channels atheism is turning the TV off.
"Religion is a culture of faith; science is a culture of doubt." ― Richard P. Feynman
'It is said that your life flashes before your eyes just before you die. That is true, it's called Life.' - Terry Pratchett
Remember, your inability to grasp science is not a valid argument against it.

Recusant

A couple of articles about how combining the CRISPR-Cas9 technique with another called a "gene drive" may be an effective tool for managing troublesome species like the anopheles mosquito and the cane toad. There are of course some profound ethical questions around this development, which seems to always be the case with these powerful genetic technologies.

"The CRISPR machines that can wipe out entire species" | c|net

QuoteCharles Darwin had no idea what a gene was. If we dropped the father of evolution into 2019, the idea that humans can willfully alter the genes of an entire species would surely seem like wizardry to him.

But CRISPR gene drives -- a new, inconceivably powerful technique that forces genes to spread through a population -- have the ability to do just that. Gene drives allow us to hone the blunt edges of natural selection for our own purposes, potentially preventing the spread of disease or eradicating invasive pests.

Yet as with any science performed at the frontier of our knowledge, we are still coming to terms with how powerful CRISPR gene drives might be. Playing the game of genomes means we may, in the future, choose which species live and which die -- a near-unbelievable capability that scientists and ethicists agree presents us with unique moral, social and ethical challenges.

[Continues . . .]

"Gene Drive" | Scientific American

QuoteResearch into a genetic engineering technology that can permanently change the traits of a population or even an entire species is progressing rapidly. The approach uses gene drives—genetic elements that pass from parents to unusually high numbers of their offspring, thereby spreading through populations rather quickly. Gene drives occur naturally but can also be engineered, and doing so could be a boon to humanity in many ways. The technology has the potential to stop insects from transmitting malaria and other terrible infections, enhance crop yields by altering pests that attack plants, render corals resistant to environmental stress, and keep invasive plants and animals from destroying ecosystems. Yet investigators are deeply aware that altering or even eliminating a species could have profound consequences. In response, they are developing rules to govern the transfer of gene drives from the laboratory into future field tests and wider use.

[Continues . . .]
"Religion is fundamentally opposed to everything I hold in veneration — courage, clear thinking, honesty, fairness, and above all, love of the truth."
— H. L. Mencken


Recusant

A call for a moratorium on editing human germlines.

"Adopt a moratorium on heritable genome editing" | Nature

QuoteWe call for a global moratorium on all clinical uses of human germline editing — that is, changing heritable DNA (in sperm, eggs or embryos) to make genetically modified children.

By 'global moratorium', we do not mean a permanent ban. Rather, we call for the establishment of an international framework in which nations, while retaining the right to make their own decisions, voluntarily commit to not approve any use of clinical germline editing unless certain conditions are met.

To begin with, there should be a fixed period during which no clinical uses of germline editing whatsoever are allowed. As well as allowing for discussions about the technical, scientific, medical, societal, ethical and moral issues that must be considered before germline editing is permitted, this period would provide time to establish an international framework.

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The story about this from Reuters quotes dissenting views:

QuoteSome scientists called the proposed ban unnecessary, saying it would not prevent a scientist bent on using the technology from editing DNA in embryos to prevent disease or enhance traits of a child, as was the case with Chinese researcher He Jiankui.

"We do not think a moratorium would have deterred He Jiankui, who acted secretively and in breach of a clear scientific consensus that germline genome editing should not be used in the clinic at this time," Sarah Norcross, director of Britain-based Progress Educational Trust, said in a statement.

Helen O'Neill, program director for Reproductive Science and Women's Health at University College London, said the proposal ignores the fact that a global ban already exists.

O'Neill said there were legal and ethical measures in place in China and that He broke many of these rules. "It was not that he did this because the law allowed it."

[Link to full article.]
"Religion is fundamentally opposed to everything I hold in veneration — courage, clear thinking, honesty, fairness, and above all, love of the truth."
— H. L. Mencken


Recusant

A different technique in the CRISPR family--Cas-3. This story isn't as dramatic as some in this thread, but it does chronicle another advance in gene editing technology.

"CRISPR-Cas3 innovation holds promise for disease cures, advancing science" | ScienceDaily

QuoteA Cornell researcher, who is a leader in developing a new type of gene editing CRISPR system, and colleagues have used the new method for the first time in human cells -- a major advance in the field.

The new system, called CRISPR-Cas3, can efficiently erase long stretches of DNA from a targeted site in the human genome, a capability not easily attainable in more traditional CRISPR-Cas9 systems. Though robust applications may be well in the future, the new system has the potential to seek out and erase such ectopic viruses as herpes simplex, Epstein-Barr, and hepatitis B, each of which is a major threat to public health.

"My lab spent the past ten years figuring out how CRISPR-Cas3 works. I am thrilled that my colleagues and I finally demonstrated its genome editing activity in human cells," said Ailong Ke, professor of molecular biology and genetics and a corresponding author of a paper published April 8 in the journal Molecular Cell. "Our tools can be made to target these viruses very specifically and then erase them very efficiently. In theory, it could provide a cure for these viral diseases."

[Continues . . .]
"Religion is fundamentally opposed to everything I hold in veneration — courage, clear thinking, honesty, fairness, and above all, love of the truth."
— H. L. Mencken


Recusant

Further progress:

"New CRISPR tool has the potential to correct almost all disease-causing DNA glitches, scientists report" | STAT

QuoteA new form of the genome-editing tool CRISPR-Cas9 appears to significantly expand the range of diseases that could be treated with the technology, by enabling scientists to precisely change any of DNA's four "letters" into any other and insert or delete any stretch of DNA — all more efficiently and precisely than previous versions of CRISPR. Crucially, scientists reported on Monday, it accomplishes all that without making genome-scrambling cuts in the double helix, as classic CRISPR and many of its offshoots do.

News about this "prime editing" began circulating among CRISPR-ites this month, when the inventors unveiled it at a meeting at Cold Spring Harbor Laboratory. Since then, "the excitement has been palpable," said genetic engineer Fyodor Urnov of the University of California, Berkeley, who was not involved in the research.

"I can't overstate the significance of this," he said, likening the creation of ever-more kinds of genome-editing technologies to the creation of superheroes with different powers: "This could be quite a useful Avenger for the genome-editing community, especially in translating basic research to the clinic" to cure diseases ranging from sickle cell to cystic fibrosis.

Prime editing's inventors, led by David Liu of the Broad Institute of MIT and Harvard and postdoctoral fellow Dr. Andrew Anzalone, say it has the potential to correct 89% of known disease-causing genetic variations in DNA, from the single-letter misspelling that causes sickle cell to the superfluous four letters that cause Tay-Sachs disease. All told, they report making 175 edits in human and mouse cells.

[Continues . . .]
"Religion is fundamentally opposed to everything I hold in veneration — courage, clear thinking, honesty, fairness, and above all, love of the truth."
— H. L. Mencken


Recusant

Noted in a post here in December of last year, He Jiankui claims to have used CRISPR-Cas9 to modify the genome of a pair of twins. He has now been sentenced to prison by a Chinese court.

"China jails scientist who gene-edited babies" | Agence France-Presse

QuoteA Chinese court on Monday sentenced the scientist who claimed to be behind the world's first gene-edited babies to three years in prison for illegal medical practice, state media reported.

He Jiankui, who shocked the scientific community last year by announcing the birth of twin girls whose genes had allegedly been altered to confer immunity to HIV, was also fined three million yuan ($430,000), Xinhua news agency said.

He, who was educated at Stanford University, was sentenced by a court in Shenzhen for "illegally carrying out the human embryo gene-editing intended for reproduction", Xinhua said.

Two of his fellow researchers were also sentenced. Zhang Renli was handed a two-year jail term and fined one million yuan while Qin Jinzhou was given 18 months, suspended for two years, and fined 500,000 yuan.

The trio had not obtained qualifications to work as doctors and had knowingly violated China's regulations and ethical principles, according to the court verdict, Xinhua said.

They had acted "in the pursuit of personal fame and gain" and seriously "disrupted medical order", it said.

The researchers had forged ethical review materials and recruited couples where the husband was HIV positive for their gene-editing experiments.

The trial was held behind closed doors as the case related to "personal privacy", Xinhua said.

[. . .]

He claimed a medical breakthrough that could "control the HIV epidemic", but it was not clear whether he had even been successful in immunising the babies against the virus because the team did not reproduce the gene mutation that confers this resistance, scientists told the MIT Technology Review.

While the team targeted the right gene, they did not replicate the "Delta 32" variation required, instead creating novel edits whose effects are not clear.

Moreover, CRISPR remains an imperfect tool because it can lead to unwanted or "off-target" edits, making its use in humans hugely controversial.

In 2015, a UN bioethics committee called for a stop to human embryo gene editing for fears it could be used to modify the human race.

But a year later Britain granted scientists permission to edit embryo DNA in research on the causes of infertility and miscarriages.

And in 2017, a US science advisory committee said such modification should be allowed in future to eliminate disease.

In November this year the World Health Organization said it would create a global registry to track research into human genetic manipulation following the backlash to He's announcement.

[Link to full story.]
"Religion is fundamentally opposed to everything I hold in veneration — courage, clear thinking, honesty, fairness, and above all, love of the truth."
— H. L. Mencken


Recusant

Some detail about the failures of He Jiankui and his team. As a bonus, the article gives a decent description of how CRISPR-Cas9 works.

"China's failed gene-edited baby experiment proves we're not ready for human embryo modification" | The Conversation

QuoteMore than a year ago, the world was shocked by Chinese biophysicist He Jiankui's attempt to use CRISPR technology to modify human embryos and make them resistant to HIV, which led to the birth of twins Lulu and Nana.

Now, crucial details have been revealed in a recent release of excerpts from the study, which have triggered a series of concerns about how Lulu and Nana's genome was modified.

[. . .]

He Jiankui and his colleagues were targeting a gene called CCR5, which is necessary for the HIV virus to enter into white blood cells (lymphocytes) and infect our body.

One variant of CCR5, called CCR5 Δ32, is missing a particular string of 32 "letters" of DNA code. This variant naturally occurs in the human population, and results in a high level of resistance to the most common type of HIV virus.

The team wanted to recreate this mutation using CRISPR on human embryos, in a bid to render them resistant to HIV infection. But this did not go as planned, and there are several ways they may have failed.

First, despite claiming in the abstract of their unpublished article that they reproduced the human CCR5 mutation, in reality the team tried to modify CCR5 close to the Δ32 mutation.

As a result, they generated different mutations, of which the effects are unknown. It may or may not confer HIV resistance, and may or may not have other consequences.

Worryingly, they did not test any of this, and went ahead with implanting the embryos. This is unjustifiable.

[Continues . . .]
"Religion is fundamentally opposed to everything I hold in veneration — courage, clear thinking, honesty, fairness, and above all, love of the truth."
— H. L. Mencken


xSilverPhinx

On now, Another Installment of Science Stand Up:



I love bad jokes ;D
I am what survives if it's slain - Zack Hemsey


Recusant

"Religion is fundamentally opposed to everything I hold in veneration — courage, clear thinking, honesty, fairness, and above all, love of the truth."
— H. L. Mencken


Recusant

A longish article about using CRISPR as a component of a SARS-CoV-2 detection test. Reads somewhat like a self-promotion, but the details of how they're using CRISPR in the test are interesting.

"Rapid home-based coronavirus tests are coming together in research labs — we're working on analyzing spit using advanced CRISPR gene editing techniques" | The Conversation

QuoteA desperately needed tool to curb the COVID-19 pandemic is an inexpensive home-based rapid testing kit that can detect the coronavirus without needing to go to the hospital.

The Food and Drug Administration has approved a few home sample collection kits but a number of researchers, including myself, are using the gene-editing technique known as CRISPR to make home tests. If they work, these tests could be very accurate and give people an answer in about an hour.

I am a biomolecular scientist with training in pharmaceutical sciences and biomedical engineering and my lab focuses on developing next-generation of technologies for detecting and treating cancer, genetic and infectious diseases.

The COVID-19 disease is caused by a coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Unlike humans which carry their genetic material encoded in DNA, the coronavirus encodes theirs in a related molecule called RNA.

My research group recently engineered a sensitive CRISPR-based technology, that we named CRISPR-ENHANCE, and used it to create a rapid test for SARS-CoV-2 RNA. Our assay works like a pregnancy test and shows two purple colored lines if the sample is positive for the virus. Using our technology, I envision developing a test kit that would allow rapid detection of SARS-CoV-2 RNA in saliva within 45-60 minutes at home without needing any expensive equipment.

[Continues . . .]
"Religion is fundamentally opposed to everything I hold in veneration — courage, clear thinking, honesty, fairness, and above all, love of the truth."
— H. L. Mencken