How does gene editing in one cell affect other cells?

How does gene editing in one cell affect other cells?

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I have read about gene editing and I have some questions concerning this technology:

  1. With gene editing, are we correcting the genes in all the cells or a single cell?

  2. If the gene editing is done for only one cell, then how (or can) it affect other genes in other cells?

Gene editing is not done on a single cell but a bunch of cells. However, it still does not affect all the cells. Gene editing/therapy for the entire organism works in these cases:

  1. Stem cells are edited, which give rise to many other somatic cells. Usually done in case of gene therapy in which the stem cells are obtained from the patient, edited and re-implanted.
  2. Some embryonic cells are edited and reimplanted in the developing embryo which gives rise to what is known as a chimeric organism (some cells in the body carry the edit while others don't). Now some of the edited cells will give rise to germ cells which in turn give rise to gametes. In the next round of breeding the chimeric parents would give rise to a fully transgenic (with edited gene) organism.
  3. For unicellular organisms, it is pretty obvious: you just use a selection marker or extensive screening to select for the cells carrying the edited gene.

Ethical issues of CRISPR technology and gene editing through the lens of solidarity

Background: The avalanche of commentaries on CRISPR-Cas9 technology, a bacterial immune system modified to recognize any short DNA sequence, cut it out, and insert a new one, has rekindled hopes for gene therapy and other applications and raised criticisms of engineering genes in future generations.

Sources of data: This discussion draws on articles that emphasize ethics, identified partly through PubMed and Google, 2014-2016.

Areas of agreement: CRISPR-Cas9 has taken the pace and prospects for genetic discovery and applications to a high level, stoking anticipation for somatic gene engineering to help patients. We support a moratorium on germ line manipulation.

Areas of controversy: We place increased emphasis on the principle of solidarity and the public good. The genetic bases of some diseases are not thoroughly addressable with CRISPR-Cas9. We see no new ethical issues, compared with gene therapy and genetic engineering in general, apart from the explosive rate of findings. Other controversies include eugenics, patentability and unrealistic expectations of professionals and the public.

Growing points: Biggest issues are the void of research on human germ cell biology, the appropriate routes for oversight and transparency, and the scientific and ethical areas of reproductive medicine.

Areas timely for developing research: The principle of genomic solidarity and priority on public good should be a lens for bringing clarity to CRISPR debates. The valid claim of genetic exceptionalism supports restraint on experimentation in human germ cells, given the trans-generational dangers and the knowledge gap in germ cell biology.

Keywords: CRISPR ethics gene editing genetic engineering germ cell mutation solidarity.

Is gene editing ethical?

If you bring up the subject of gene editing, the debate is sure to become heated. But are we slowly warming to the idea of using gene editing to cure genetic diseases, or even create “designer babies?”

Share on Pinterest Will gene editing become a part of everyday medicine?

Gene editing holds the key to preventing or treating debilitating genetic diseases, giving hope to millions of people around the world. Yet the same technology could unlock the path to designing our future children, enhancing their genome by selecting desirable traits such as height, eye color, and intelligence.

While gene editing has been used in laboratory experiments on individual cells and in animal studies for decades, 2015 saw the first report of modified human embryos.

The number of published studies now stands at eight, with the latest research having investigated how a certain gene affects development in the early embryo and how to fix a genetic defect that causes a blood disorder .

The fact that gene editing is possible in human embryos has opened a Pandora’s box of ethical issues.

So, who is in favor of gene editing? Do geneticists feel differently about this issue? And are we likely to see the technology in mainstream medicine any time soon?

Gene editing is the modification of DNA sequences in living cells. What that means in reality is that researchers can either add mutations or substitute genes in cells or organisms.

While this concept is not new, a real breakthrough came 5 years ago when several scientists saw the potential of a system called CRISPR/Cas9 to edit the human genome.

CRISPR/Cas9 allows us to target specific locations in the genome with much more precision than previous techniques. This process allows a faulty gene to be replaced with a non-faulty copy, making this technology attractive to those looking to cure genetic diseases.

The technology is not foolproof, however. Scientists have been modifying genes for decades, but there are always trade-offs. We have yet to develop a technique that works 100 percent and doesn’t lead to unwanted and uncontrollable mutations in other locations in the genome.

In a laboratory experiment, these so-called off-target effects are not the end of the world. But when it comes to gene editing in humans, this is a major stumbling block.

Here, the ethical debate around gene editing really gets off the ground.

When gene editing is used in embryos — or earlier, on the sperm or egg of carriers of genetic mutations — it is called germline gene editing. The big issue here is that it affects both the individual receiving the treatment and their future children.

This is a potential game-changer as it implies that we may be able to change the genetic makeup of entire generations on a permanent basis.

Dietram Scheufele — a professor of science communication at the University of Wisconsin-Madison — and colleagues surveyed 1,600 members of the general public about their attitudes toward gene editing. The results revealed that 65 percent of respondents thought that germline editing was acceptable for therapeutic purposes.

When it came to enhancement, only 26 percent said that it was acceptable and 51 percent said that it was unacceptable. Interestingly, attitudes were linked to religious beliefs and the person’s level of knowledge of gene editing.

“Among those reporting low religious guidance,” explains Prof. Scheufele, “a large majority (75 percent) express at least some support for treatment applications, and a substantial proportion (45 percent) do so for enhancement applications.”

He adds, “By contrast, for those reporting a relatively high level of religious guidance in their daily lives, corresponding levels of support are markedly lower (50 percent express support for treatment 28 percent express support for enhancement).”

Among individuals with high levels of technical understanding of the process of gene editing, 76 percent showed at least some support of therapeutic gene editing, while 41 percent showed support for enhancement.

But how do the views of the general public align with those of genetics professionals? Well, Alyssa Armsby and professor of genetics Kelly E. Ormond — both of whom are from Stanford University in California — surveyed 500 members of 10 genetics societies across the globe to find out.

Armsby says that “there is a need for an ongoing international conversation about genome editing, but very little data on how people trained in genetics view the technology. As the ones who do the research and work with patients and families, they’re an important group of stakeholders.”

The results were presented yesterday at the American Society for Human Genetics (ASHG) annual conference, held in Orlando, FL.

In total, 31.9 percent of respondents were in favor of research into germline editing using viable embryos. This sentiment was more particularly pronounced in respondents under the age of 40, those with fewer than 10 years experience, and those who classed themselves as less religious.

The survey results also revealed that 77.8 percent of respondents supported the hypothetical use of germline gene editing for therapeutic purposes. For conditions arising during childhood or adolescence, 73.5 percent were in favor of using the technology, while 78.2 percent said that they supported germline editing in cases where a disease would be fatal in childhood.

On the subject of using gene editing for the purpose of enhancement, just 8.6 percent of genetics professionals spoke out in favor.

“I was most surprised, personally,” Prof. Ormond told Medical News Today, “by the fact that nearly [a third] of our study respondents were supportive of starting clinical research on germline genome editing already (doing the research and attempting a pregnancy without intent to move forward to a liveborn baby).”

This finding is in stark contrast to a policy statement that the ASHG published earlier this year, she added.

According to the statement — of which Prof. Ormand is one of the lead authors — germline gene editing throws up a list of ethical issues that need to be considered.

The possibility of introducing unwanted mutations or DNA damage is a definite risk, and unwanted side effects cannot be predicted or controlled at the moment.

The authors further explain:

“ Eugenics refers to both the selection of positive traits (positive eugenics) and the removal of diseases or traits viewed negatively (negative eugenics). Eugenics in either form is concerning because it could be used to reinforce prejudice and narrow definitions of normalcy in our societies.”

“This is particularly true when there is the potential for ‘enhancement’ that goes beyond the treatment of medical disorders,” they add.

While prenatal testing already allows parents to choose to abort fetuses carrying certain disease traits in many places across the globe, gene editing could create an expectation that parents should actively select the best traits for their children.

The authors take it even further by speculating how this may affect society as a whole. “Unequal access and cultural differences affecting uptake,” they say, “could create large differences in the relative incidence of a given condition by region, ethnic group, or socioeconomic status.”

“Genetic disease, once a universal common denominator, could instead become an artefact of class, geographic location, and culture,” they caution.

Therefore, the ASHG conclude that at present, it is unethical to perform germline gene editing that would lead to the birth of an individual. But research into the safety and efficacy of gene editing techniques, as well as into the effects of gene editing, should continue, providing such research adheres to local laws and policies.

In Europe, this is echoed by a panel of experts who urge the formation of a European Steering Committee to “assess the potential benefits and drawbacks of genome editing.”

They stress the need “to be proactive to prevent this technology from being hijacked by those with extremist views and to avoid misleading public expectation with overinflated promises.”

But is the public’s perception really so different from that of researchers on the frontline of scientific discovery?

CRISPR gene editing used to store data in DNA inside living cells

DNA inside living bacterial cells has been edited with CRISPR technology to encode and store information. This could be a step towards developing a new medium for long-term data storage.

Life’s genetic information is stored in DNA, but there is growing interest in using DNA as a storage medium for other kinds of data. To do this, information is often encoded using the four DNA bases – adenine (A), cytosine (C), thymine (T) and guanine (G). The corresponding DNA sequence can then be chemically synthesised in a laboratory, and even stored within everyday objects.

Harris Wang at Columbia University in New York and his team took this one step further, using a form of CRISPR gene editing to insert specific DNA sequences that encode binary data – the 1s and 0s that computers use to store data – into bacterial cells. By assigning different arrangements of these DNA sequences to different letters of the English alphabet, the researchers were able to encode the 12-byte text message “hello world!” into DNA inside E. coli cells.


Wang and his team were subsequently able to decode the message by extracting and sequencing the bacterial DNA.

Read more: DNA coated with silica could store masses of data in a single gram

“This field is progressing exponentially and this paper is a great example,” says George Church at Harvard University, who wasn’t involved with the work.

Wang thinks DNA inside living cells could be a more stable medium for long-term storage in unpredictable conditions. Whereas DNA kept outside cells can be degraded, bacteria have the ability to adapt to changing surroundings and can survive under harsh conditions. “What you’re offering by putting it inside the cell is that the DNA is protected by the cell and the machinery that the cell has to protect its DNA,” says Wang.

“This can be very interesting for long-term storage,” says Thomas Heinis at Imperial College London. But as bacteria adapt and change, their DNA changes too – and these changes could affect the encoded information, says Heinis. “There are many sources of errors, one major source being mutations in the DNA during cell replication,” he says.

“They are a very long way from having a working system that replaces our digital devices,” says Nick Goldman at EMBL-European Bioinformatics Institute in Cambridge, UK. “But it’s a little step along the way to something that might do that.”

Journal reference: Nature Chemical Biology, DOI: 10.1038/s41589-020-00711-4

CRISPR gene editing explained: What is it and how does it work?

Everything you need to know about the gene-editing breakthrough that one day could cure disease, eradicate species and build designer babies.

We are in the midst of a gene-editing revolution.

For four decades, scientists have tinkered with our genes. Since the 1970s, they've experimentally switched them on and off, uncovering their functions mapped their location within our genome and even inserted or deleted them in animals, plants and human beings.

And in November 2018, a Chinese scientist claimed to have created the world's first genetically modified human beings.

Though scientists have made great inroads into understanding human genetics, editing our genes has remained a complex process requiring imprecise, expensive technology, years of expertise and just a little luck, too.

In 2012, a pair of scientists developed a new tool to modify genes, reshaping the entire field of gene-editing forever: CRISPR. Often described as "a pair of molecular scissors," CRISPR is widely considered the most precise, most cost-effective and quickest way to edit genes. Its potential applications are far-reaching, affecting conservation, agriculture, drug development and how we might fight genetic diseases. It could even alter the entire gene pool of a species.

The field of CRISPR research is still remarkably young, yet we've already seen how it might be used to fight HIV infection, combat invasive species and destroy antibiotic-resistant bacteria. Many unknowns remain, however, including how CRISPR might damage DNA, leading to pathologies such as cancer.

Such a monumental leap in genetic engineering is full of complexities that ask big, often philosophical questions about science, ethics, how we conduct research and the future of humanity itself. With the confirmation that two human embryos were modified using CRISPR and carried to term, those questions have come sharply into focus. The future of gene-editing seemingly arrived overnight.

But what exactly is CRISPR and what are the outstanding concerns about such a powerful tool?

CRISPR has the potential to be used in editing human embryos to create "designer babies."

Science Photo Library/Getty Images

What is CRISPR?

Few predicted how important CRISPR would become for gene editing upon its discovery 30 years ago.

As early as 1987, researchers at Osaka University studying the function of Escherichia coli genes first noticed a set of short, repeated DNA sequences, but they didn't understand the significance.

Six years later, another microbiologist, Francisco Mojica, noted the sequences in a different single-celled organism,
Haloferax mediterranei. The sequences kept appearing in other microbes and in 2002, the unusual DNA structures were given a name: Clustered regularly interspaced short palindromic repeats.

Studying the sequences more intensely revealed that CRISPR forms an integral part of the "immune system" in bacteria, allowing them to fight off invading viruses. When a virus enters the bacteria, it fights back by cutting up the virus' DNA. This kills the virus and the bacteria stores some of the leftover DNA.

The leftover DNA is like a fingerprint, stored in the CRISPR database. If invaded again, the bacteria produce an enzyme called Cas9 that acts like a fingerprint scanner. Cas9 uses the CRISPR database to match the stored fingerprints with those of the new invader. If it can find a match, Cas9 is able to chop up the invading DNA.

/>Eric Mack

How is CRISPR used to edit genes?

Nature often provides great templates for technological advances. For instance, the nose of a Japanese bullet train is modeled on the kingfisher's beak because the latter is expertly "designed" by evolution to minimize noise as the bird dives into a stream to catch fish.

In a similar way, CRISPR/Cas9's ability to efficiently locate specific genetic sequences, and cut them, inspired a team of scientists to ask whether that ability could be mimicked for other purposes.

The answer would change gene editing forever.

In 2012, pioneering scientists Jennifer Doudna, from UC Berkeley, and Emmanuelle Charpentier, at Umea University Sweden, showed CRISPR could be hijacked and modified. Essentially, they'd turned CRISPR from a bacterial defense mechanism into a DNA-seeking missile strapped to a pair of molecular scissors. Their modified CRISPR system worked marvelously well, finding and cutting any gene they chose.

An illustration of the CRISPR-Cas9 gene editing complex. The Cas9 nuclease protein (white and green) uses a guide RNA (red) sequence to cut DNA (blue) at a complementary site.

Molekull/Science Photo Library/Getty

Several research groups followed up on the original work, showing that the process was possible in yeast and cultured mouse and human cells.

The floodgates opened, and CRISPR research, which had long been the domain of molecular microbiologists, skyrocketed. The number of articles referencing CRISPR in preeminent research journal Nature has increased by over 6,000 percent between 2012 and 2018.

While other gene-editing tools are still in use, CRISPR provides a gigantic leap because of its precision and reliability. It's really good at finding genes and making accurate cuts. That allows genes to be cut out with ease, but it also provides an opportunity to paste new genes into the gap. Previous gene-editing tools could do this, too, but not with the ease that CRISPR can.

Another huge advantage CRISPR has over alternative gene-editing techniques is its expense. While previous techniques might cost a laboratory upward of $500 to edit a single gene, a CRISPR kit can do the same thing for under $100.

What can CRISPR do?

The CRISPR/Cas9 system has been adapted to enable gene editing in organisms including yeast, fungi, rice, tobacco, zebrafish, mice, dogs, rabbits, frogs, monkeys, mosquitoes and, of course, humans -- so its potential applications are enormous.

For research scientists, CRISPR is a tool that provides better, faster tinkering with genes, allowing them to create models of disease in human cell lines and mouse models with much higher proficiency. With better models of say, cancer, researchers are able to fully understand the pathology and how it develops, and that could lead to improved treatment options.

One particular leap in cancer therapy options is the genetic modification of T cells, a type of white blood cell that's critical for the human immune system. A Chinese clinical trial extracted T cells from patients, used CRISPR to delete a gene that usually acts as an immune system brake, and then reintroduced them into the patients in an effort to combat lung cancer. And that's just one of the many trials underway using CRISPR edited cells to fight particular types of cancer.

Beyond cancer, CRISPR has the potential to treat diseases caused by a mutation in a single gene, such as sickle cell anemia or Duchenne muscular dystrophy. Correcting a defective gene is known as gene therapy, and CRISPR is potentially the most powerful way to perform it. Using mouse models, researchers have demonstrated the efficacy of such treatments but human gene therapies using CRISPR remain untested.

Mosquitoes will be targeted using CRISPR gene drives, which could potentially drive malaria-carrying species to extinction.

Crisanti Lab/Alekos Simoni

Then there are CRISPR gene drives , which use CRISPR to guarantee a genetic trait will be passed from parent to offspring -- essentially rewriting the rules of inheritance. Guaranteeing certain genes will spread through a population provides an unprecedented opportunity to tackle mosquito-borne diseases such as malaria, enabling scientists to create infertile mosquitoes in the lab and release them in the wild to crash the population -- or even render a species extinct. CNET published an extensive report of their proposed use and the ethical concerns that surround them in February 2019.

And CRISPR's potential benefits don't end there. The tool opens up new ways of creating antimicrobials to combat rising levels of antibiotic resistance, targeted manipulation of agricultural crops such as wheat to make them hardier or more nutritious, and, potentially, the ability to design human beings, gene by gene.

CRISPR concerns

CRISPR may be the most precise way to cut DNA we've yet discovered, but it's not always perfect.

One of the chief barriers to getting CRISPR effectively working in humans is the risk of "off-target effects." When CRISPR is tasked with hunting down a gene, it sometimes finds genes that look very similar to its target and cuts them, too.

An unintended cut may cause mutations in other genes, leading to pathologies such as cancer, or it may have no effect at all -- but with safety a major concern, scientists will need to ensure CRISPR acts only on the gene it's intended to impact. This work has already begun, and several teams of researchers have tinkered with CRISPR/Cas9 to increase its specificity.

To date, CRISPR work in humans has been confined to cells that don't pass on their genome to the next generation. But gene editing can also be used to edit embryos and thus, change the human gene pool. In 2015, an expert panel of CRISPR scientists suggested that such editing -- known as germline editing -- would be irresponsible until consensus can be reached on safety, efficacy, regulation and social concerns.

Still, research into germline editing has been occurring for several years. In 2017, scientists in the UK edited human embryos for the first time, and researchers in the US used CRISPR to correct a defective gene that causes heart disease. The ability to edit embryos begins to raise ethical concerns about so-called designer babies, wherein scientists may select beneficial genes to increase physical fitness, intelligence or muscle strength, creeping into the controversial waters of eugenics.

That particular future is likely a long way off -- but the era of editing the human genome has already begun.

Editing humans

On Nov. 25, 2018, Chinese scientist Jiankui He said he had created the world's first CRISPR babies. By using CRISPR, He was able to delete a gene known as CCR5. The modified embryos resulted in the birth of twin girls, known by the pseudonyms Lulu and Nana.

The scientific community widely condemned the research, criticizing He's lack of transparency and asking whether there was an unmet medical need for the two girls to receive such a modification. In the wake of the research, several high-profile researchers involved with CRISPR's creation even suggested a global moratorium on using the tool for germline editing.

Few would argue that He's work highlights a need for stricter regulatory controls and effective oversight of clinical trials in which embryos are edited. While He maintains his own experiment was concerned with improving the health of the twin girls by making them HIV-resistant, the experiment was deemed reckless and ethically wrong and the potential consequences overlooked. Recent research suggests that the deletion He created in the CCR5 gene may affect brain activity, after a study in mice showed that blocking CC5 improves cognition and recovery from stroke.

In January 2019, the Chinese government said that He acted both unlawfully and unethically and would face charges. He was later dismissed by his university.

Jiankui He claimed to have created the world's first gene-edited babies.

The most recent International Summit for Human Genome Editing, in November 2018, concluded, as it did in 2015, "the scientific understanding and technical requirements for clinical practice remain too uncertain and the risks too great to permit clinical trials of germline editing at the time."

He's work, which remains unpublished, heralds the first clinical trial and birth of genetically modified human beings -- which means, whether it was the intention or not, a new era for CRISPR has begun.

As the revolution surges forward, the greatest challenges will continue to be effective oversight and regulation of the technology, the technical hurdles that science must overcome to ensure it is precise and safe, and managing the larger societal concerns of tinkering with the stuff that makes us us.

Recent advances

CRISPR continues to make headlines as scientists refine its specificity and turn it toward myriad genetic diseases. On Feb. 4, researchers at UC Berkeley, including CRISPR pioneer Jennifer Douda, revealed that another enzyme, CasX, could be used to edit genes in place of Cas9.

The scientists identified CasX in a ground-dwelling bacteria not normally present in humans, which means our immune systems are less likely to rebel against it. Because it's smaller and potentially more specific than Cas9, it can clip genes with greater success and less chance of any negative effects.

Then, on Feb. 18, scientists at UC San Francisco revealed they had used CRISPR to make stem cells "invisible" to the immune system. Stem cells are able to mature into adult cells of any tissue, so they have been proposed as a way to repair damaged organs. However, the immune system typically tries to annihilate any foreign invader and stem cells are seen as such. CRISPR has enabled the stem cells to evade the immune system so they can get to work at healing.

Only a day later, researchers at the Salk Institute for Biological Sciences published in Nature Medicine their findings on a CRISPR therapy for Hutchinson-Gilford progeria, a disease associated with rapid aging. The disease is caused by a genetic mutation that results in a buildup of abnormal proteins, ultimately leading to premature cell death. A single dose of CRISPR/Cas9 was shown to suppress the disease in a mouse model, paving the way for further exploration of CRISPR's therapeutic potential.

And still more CRISPR success stories continue to roll in. On Feb. 25, CRISPR Therapeutics, a company co-founded by CRISPR visionary Emmanuelle Charpentier, announced that the first human patients had been infused with a CRISPR/Cas9 drug to treat the disease beta-thalassemia. The illness is caused by a genetic mutation that results in red blood cells being unable to create the oxygen-transport molecule haemoglobin. To combat this, the CRISPR Therapeutics team takes stem cells from a patient, edits them with CRISPR/Cas9 outside the body to increase haemoglobin production and then transfuses them back into the bloodstream. The company plans to use a similar approach to treating the blood disease known as sickle cell anemia.

CRISPR research is advancing at a rapid pace, and it can be hard to keep up. In only seven years, CRISPR went from an evolutionary adaptation in bacteria to a gene-editing tool that created the very first genetically modified human beings. We've already seen CRISPR transform the entire field of molecular biology and that effect has rippled across the biological and medical fields.

3 big questions about human gene editing

Researchers from around the world came together in Washington, DC, this week to discuss the rapidly developing technology of human gene editing.

At the International Summit on Human Gene Editing, hosted by the U.S. National Academy of Sciences in Washington, the Chinese Academy of Sciences and the UK's Royal Society, much discussion surrounded a newly developed gene editing biotechnology called CRISPR -- derived from a bacterial protein -- that lets scientists clip away or tweak specific portions of DNA.

It has the potential to help get rid of certain diseases by splicing out defective snippets of our genes. But because of the unknown long-term impact, some leading scientists are calling for a moratorium on its use.

At the summit, a handful of key issues came up again and again: What types of diseases could be treated with human gene editing technologies? What potential risks and side effects could there be? And what are the ethical issues surrounding the new technology?

CBS News spoke with experts from various areas of medicine, most who attended the summit, about these big questions.

What diseases could be cured?

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"Basically, you're going to be looking at genetic diseases where you're looking at a single gene and you'll go in and disrupt or replace the malfunctioning gene," said Françoise Baylis, a philosopher and bioethicist at Dalhousie University in Halifax, Canada.

Cystic fibrosis, polycystic kidney disease, hemophilia, Tay-Sachs disease, and some breast cancers are among the conditions scientists might first look to treat, explained Dr. Arthur Caplan, founding director of the division of medical ethics at NYU Langone Medical Center's Department of Population Health.

"They're called point mutations. They're the first places you'd try to go," Caplan said.

But scientists believe that's only the beginning. "I hope that there will be a move beyond, to more complex diseases and disorders," Baylis, a member of the organizing committee for this week's summit, told CBS News.

She pointed out that the meeting was divided into discussions about two types of gene editing therapies: Somatic (non-reproductive) cell therapy, which involves treating individual sick people, and the more controversial germ line therapy, which involves editing genetic material in embryos.

Baylis said the CRISPR advances make more "fanciful" ideas about using gene editing for human enhancement "seem all the more possible," too.

Caplan said that back in the late seventies, scientists swore they'd never touch the germ line -- embryos.

"They were terrified it was eugenics, Nazi Germany. In order to keep people calm, scientific leaders said, 'Whatever we do with genetic changes, we're just going to stick with somatic cells , don't worry about it, we're never going do that.'"

But Caplan said that's always what scientists say when they don't have the ability to do something now, with an editing tool such as CRISPR, the conversation is changing.

Does that mean scientists will be able to engineer changes to eye or skin color, or give people mega-strength?

Maybe, said Caplan. "I think it's reasonable to presume you could tweak things for strength, more muscles, endurance, or to be able to run or travel further." You might be able to enhance memory, to make a person able to retain more or learn faster, he said.

Someday, he said, "I think you could tweak genes that would allow you to perceive more. You might be able to see more like a bat, sense more of the radiation spectrum. See ultraviolet light and parts of the energy spectrum we don't see but that other creatures do. Eagle-eye vision."

"You could certainly make people more disease resistant, less likely to get a cold or the flu. Or to fight off MRSA or E. coli -- build up their immune systems. Enhance them so they could enjoy more pleasure. They've been doing a teeny, tiny bit in animals," said Caplan, who will lead sessions on ethical and regulatory issues of gene editing in animal research next week in Washington, DC.

But such knowledge is still years away, he added, and scientists at the summit made it clear that the aim of the new technology is to heal the sick.

Dr. Mitchell Weiss, chair of the hematology department at St. Jude Children's Research Center, told CBS News that somatic therapies to treat individual patients are already being tested in clinical trials.

He said the technology has the potential to treat conditions such as HIV, hemophilia, sickle cell anemia, and some forms of cancer.

"Genome editing directed toward bone marrow is another application," he said. The bone marrow can be removed, genetically edited in the lab, and then returned to the body. This technique, he said, may lower the health risks of a current treatment option for children with sickle cell anemia, an inherited condition in which there aren't enough healthy red blood cells to carry enough oxygen throughout the body, for example.

What are the health risks?

The main worry about CRISPR is the same worry you'd have using any gene therapy, Weiss said: "You mess around with the genome, and are you going to shut off something important or turn on something bad?"

Past investigational gene therapy led to cancer in some patients, he said.

"The major risk that people are concerned about -- there are different kinds of risk -- but the most significant right now is 'off-target' side effects," said Pilar Ossorio, professor of law and bioethics at the Morgridge Institute for Research at the University of Wisconsin-Madison.

She said once you put a CRISPR gene editing "tool" into a person's body, it can travel throughout the body and might get into other cells that you're not targeting. So the aim will be to figure out how to apply the gene editing only to the cells and tissues that scientists want to hit, without affecting anything else.

"Cells are dying all the time. If all it does is cause a cell here or there to cease to function, though, that will probably not be noticeable," Ossorio said.

What are the ethical issues - and potential for abuse?

"Our traditional ways of understanding risk and benefit completely apply. We have to make those calculations whenever we use a new kind of therapy," said Ossorio.

More risk may be acceptable for patients who have no other good treatment options. "For medical applications, the first applications are that we are trying to treat a disease. There is a human being in front of you who has a very serious disease, and you wouldn't start studying this technology in a person unless that person didn't have alternatives. Maybe existing therapies didn't work for them or there are no existing therapies," Ossorio said.

In somatic cells, gene editing will not be transmitted down to future generations, she said.

However, Caplan pointed out, it's not clear yet how germ line gene editing will affect future generations. It's possible that those genetic changes could be passed down when the person has children.

Kyle Orwig, the director of the Molecular, Genetics, and Developmental Biology Program at the University of Pittsburgh School of Medicine said, "My ethics are mostly focused on medical need and safety and efficacy. If you haven't proven safety and efficacy in animal models, you shouldn't proceed to clinical trials. And if you have, you should. And don't make trials any bigger than they need to be," to avoid exposing more people to any potential risks.

He added, "There's the claim that ethics go beyond safety and efficacy. That's there's some kind of slippery slope, but I think most of these arguments disappear once safety and efficacy is shown."

"It's good these discussions are taking place," Caplan said. "At the same time, I think we've got to be realistic. Better than fighting about bans or prohibitions, is to fight about what rules we want in order to try to fix disease in the germ line."

Another concern raised at the summit involved social justice -- equity when it comes to medical care. Gene editing technologies are costly and many experts said they're concerned that patients who might benefit from them would not have access. Weiss said sickle cell anemia, for example, one of his areas of expertise, impacts many inner city and low-income patients, not to mention those in the developing world.

"If you live in Africa or under-developed countries, health care is very different," he said.

But Caplan said disparity will not slow down technological innovation in this case, and rarely does.

"The equity thing will not work as an argument. Right now there are kids in New York City going to the finest prep schools and in Mississippi, there are kids who don't have books," he said. "Some people get care at the Mayo Clinic and some people don't have health insurance. We have neonatal care rescuing babies here in the U.S. yet many children in Africa are dying of diarrhea. I don't think it will hold things up. It would be more reasonable to try and set things up so that disease repair by gene editing is more affordable."

After three days of intensive discussion, the members of the organizing committee for the International Summit on Human Gene Editing issued a statement of conclusions. They called for more "intensive" basic science research, and for the use of existing and evolving regulatory frameworks for somatic cell clinical investigations. They also highlighted the need to address the complex issues that relate to germ line editing, and the importance of ongoing discussions as the science moves forward.

Researchers' algorithm to make CRISPR gene editing more precise

It eventually became a Nobel prize-winning revolution when researchers first engineered CRISPR as a gene editing technology for bacterial, plant, animal and human cells. The potential of the technology is great and span from curing genetically disposed diseases to applications in agricultural and industrial biotechnology, but there are challenges.

One such challenge consists of selecting a so-called gRNA molecule which should be designed to guide the Cas9 protein to the right location in the DNA where it will make a cut in relation to the gene editing.

"Typically, there are multiple possible gRNAs and they are not all equally efficient. Therefore, the challenge is to select the few that work with high efficiency and that is precisely what our new method does," says Yonglun Luo, Associate Professor Department of Biomedicine at Aarhus University.

The new method is developed from the researchers' new data and implementation of an algorithm, which gives a prediction on what gRNAs that work most efficiently.

"By combining our own data with publicly available data and including knowledge on the molecular interactions between gRNA, DNA and the CRISPR-Cas9 protein, we have succeeded in developing a better method," says Jan Gorodkin, professor at the Department of Veterinary and Animal Sciences at the University of Copenhagen.

Data, deep learning molecular interactions

Jan Gorodkin's research group with Giulia Corsi and Christian Anthon have collaborated with Yonglun Luo's research group in order to achieve the new results. The experimental part of the study was conducted by Luo's group while Gorodkin's group spearheaded the computer modelling.

"In our study, we have quantified the efficiency of gRNA molecules for more than 10,000 different sites. The work was achieved using a massive, high throughput library-based method, which would not be possible with traditional methods," says Yonglun Luo.

The researchers took their starting point concerning data generation in the concept of having a virus express gRNA and a synthetic target site in one cell at a time. The synthetic target sites have exactly the same DNA sequences as the corresponding target sites in the genome. Thus, these synthetic target sites are used as so-call surrogate target sites to capture the CRISPR-Cas9 editing efficiency. Together with colleagues from Lars Bolund Institute of Regenerative Medicine in BGI-Research and Harvard Medical School, they generated high quality CRISPR-Cas9 activity for over 10,000 gRNAs.

With this dataset of gRNAs with known efficiencies from low to high, the researchers were able to construct a model that could predict efficiencies of gRNAs which has not been seen before.

"In order to train an algorithm to become precise, one has to have a large dataset. With our library of viruses, we have obtained data that constitutes the perfect starting point for training our deep learning algorithm to predict the efficiency of gRNAs for gene editing. Our new method is more precise than other methods currently available," says Jan Gorodkin.

What will happen to He — and the children?

He has been criticized, but not just because he pursued germline editing. He also neglected to do adequate safety testing and failed to follow standard procedures in procuring participants. He was subsequently censured by the health ministry in Guangdong, where he worked, and fired from his university. He did not respond to Nature’s multiple attempts to contact him.

At this point, further penalties seem to be in the hands of the police. There are a range of criminal charges that He could face. While recruiting participants, He and his team agreed to cover the costs of fertility treatment and related expenses, up to 280,000 yuan (US$42,000). He also stipulated that participants would have to repay costs if they dropped out. Liu Ye, a lawyer at the Shanghai Haishang Law Firm, says that if such payments are found to count as coercive measures, they could constitute a crime. Guangdong province also found that He used forged ethics-review documents during recruitment of participants and swapped blood samples to skirt laws against allowing people with HIV to use assisted reproductive technologies.

Why were scientists silent over gene-edited babies?

He claims to have disabled a gene called CCR5, which encodes a protein that allows HIV to enter cells. He was aiming to mimic a mutation that exists in about 10% of Europeans, and helps to protect them from HIV infection. But He might have inadvertently caused mutations in other parts of the genome, which could have unpredictable health consequences. (He claims to have found no such mutations.) Also, CCR5 is thought to help people fight off the effects of various other infections, such as West Nile virus. If the gene is disabled, the girls could be vulnerable. If they do suffer in a way that is linked to He’s procedure, and He is found to have been practising medicine illegally, he could be sentenced to between three and ten years in prison, says Zhang Peng, a criminal-law scholar at Beijing Wuzi University. But identifying those health effects could take years.

He promised to follow up with the girls until they were 18 years old, but it is unlikely that the health ministry, which ordered He to stop doing science, will allow him to be involved in the evaluations. It is not known what, if any, special measures are being taken to look out for the girls’ health or to track the other pregnancy.

Crispr Gene Editing Can Cause Unwanted Changes in Human Embryos, Study Finds

Instead of addressing genetic mutations, the Crispr machinery prompted cells to lose entire chromosomes.

A powerful gene-editing tool called Crispr-Cas9, which this month nabbed the Nobel Prize in Chemistry for two female scientists, can cause serious side effects in the cells of human embryos, prompting them to discard large chunks of their genetic material, a new study has found.

Administered to cells to repair a mutation that can cause hereditary blindness, the Crispr-Cas9 technology appeared to wreak genetic havoc in about half the specimens that the researchers examined, according to a study published in the journal Cell on Thursday.

The consequences of these errors can be quite serious in some cases, said Dieter Egli, a geneticist at Columbia University and an author of the study. Some cells were so flummoxed by the alterations that they simply gave up on trying to fix them, jettisoning entire chromosomes, the units into which human DNA is packaged, Dr. Egli said.

“We’re often used to hearing about papers where Crispr is very successful,” said Nicole Kaplan, a geneticist at New York University who was not involved in the study. “But with the amount of power we hold” with this tool, Dr. Kaplan said, it is crucial “to understand consequences we didn’t intend.”

Crispr-Cas9, a scissorslike chemical tool that can precisely cut and customize stretches of genetic material, such as human DNA, stoked international controversy in 2018 when He Jiankui, a Chinese scientist, used the technology to yield the world’s first gene-edited infants. The experiment was widely condemned as irresponsible and dangerous — in large part because many of the ways in which Crispr-Cas9 can affect cells remain poorly understood. Dr. He was found guilty of conducting illegal medical practices in China and sentenced to three years in prison.

The new paper’s findings further underscore that “it’s really too soon to be applying Crispr to reproductive genetics,” said Nita Farahany, a bioethicist at Duke University who was not involved in the study.

Crispr-Cas9 treatments have already been given directly to people to treat conditions like blindness — a potential cure that affects that patient, and that patient only. But modifications made to sperm, eggs and embryos can be passed to future generations, raising the stakes for any mistakes made along the way.

Although scientists have been tinkering with genomes for decades, Crispr-Cas9 can accomplish a precise type of genetic surgery that other tools cannot.

Scientists can use Crispr-Cas9 to home in on a specific region of the genome and snip it in two. Sensing trouble, the cell rushes to heal its genetic wound, sometimes using a similar-looking stretch of nearby, intact DNA as a template as it stitches the pieces back together. This gives researchers an opportunity to splice in a tailor-made template of their own, in the hopes that the cell will incorporate the intended change.

In 2017, a team of researchers led by Shoukhrat Mitalipov, a geneticist at Oregon Health and Science University in Portland, reported that human embryos carrying a mutation could be coaxed into this process without a synthetic template. The researchers generated embryos from a union between two cells: a sperm carrying a mutation that can make it harder for the heart to pump blood, and an egg with a healthy version of the gene. Dr. Mitalipov and his team used Crispr-Cas9 to cut the broken copy of the gene to see if the intact version would guide its repair. They reported the experiment a success and published it in the journal Nature.

“In principle, this could be a way to correct a mutation in a human embryo” that has only one broken copy of a gene, Dr. Egli said.

But the new findings could cast some doubt on the 2017 work, Dr. Egli added.

The researchers of the Cell study focused on a different mutation — one that causes hereditary blindness and affects a different part of the genome — but adopted a similar setup. Using donated sperm containing a mutation in a gene called EYS, they fertilized eggs that had normal copies of EYS, then sent in Crispr-Cas9 to snip the mutation.

Several of the cells managed to sew the Crispr-cut pieces of DNA back together with a few minor changes, Dr. Egli said.

But about half the embryos seemed unable to cope with the trauma of the break. The genetic damage failed to heal, eventually forcing cells to tear off and toss aside large chunks of the chromosome that harbored the mutated EYS. In some cells, the entire chromosome was lost.

“That is not a correction,” Dr. Egli said. “That is a vastly different outcome.”

Instead of gently goading the cell into editing the genetic “text” at which it was targeted, the Crispr machinery gouged irreparable gaps in cells’ DNA, said Maria Jasin, a geneticist at Memorial Sloan Kettering Cancer Center and another author of the study. The negative consequences of this, she added, were disproportionately disastrous. “They were talking about trying to repair one gene, and you have a substantial fraction of the genome being changed,” Dr. Jasin said.

Dr. Egli and Dr. Jasin said that this probably happened in Dr. Mitalipov’s 2017 paper as well, but it went unnoticed. After Dr. Mitalipov’s team carried out their Crispr-Cas9 treatment, they could no longer detect the mutation in embryos. But Dr. Egli and Dr. Jasin noted that, technically, dumping or destroying a huge segment of a chromosome would have wiped out evidence of the mutation as well. Dr. Mitalipov and his team, they said, might have mistaken a deletion for an edit.

Dr. Mitalipov disagreed with this interpretation, and he said the new paper’s conclusions were not fully backed up by the necessary data. “They don’t have evidence to show these are deletions,” he said. Far more complex experiments, he said, would be needed to conclusively distinguish a “corrected” chromosome from an absent one.

Dr. Kaplan, of New York University, said she found the new paper’s findings convincing. And she, like all of the other experts who spoke with The New York Times, echoed a crucial sentiment: that Crispr-editing embryos in the clinic must remain a far-off reality, if it is ever approved at all.

“At this point, it’s too dangerous,” Dr. Jasin said. “We’re just not sure which way things are going to go.”

The U.S. government does not permit the use of federal funds to conduct research on human embryos. Dr. Egli’s team sought private funding from the New York Stem Cell Foundation and the Russell Berrie Foundation Program in cellular therapies to run its experiments.

Other Crispr-based technologies exist that could circumvent several of the issues the team identified. For example, some researchers have developed techniques that allow them to make less drastic cuts to the genome and tinker with just one genetic letter at a time.

Given his team’s findings, Dr. Egli also floated the idea that the blunter version of Crispr-Cas9 could someday be deployed as a sort of molecular bomb: shredding and eliminating unwanted, extra chromosomes when they appear in embryos.

Dr. Farahany, of Duke University, urged caution. The new study, she said, only builds upon the notion that scientists will need to walk, not run, in developing Crispr tools for reproductive medicine.

“We have a long way to go,” Dr. Farahany said. “Until we can figure out what the off-target effects are, and how we can control for them,” embryo editing of any kind “would be deeply unethical.”

How does gene editing in one cell affect other cells? - Biology

Genome editing is a way of making changes to specific parts of a genome. Scientists have been able to alter DNA since the 1970s, but in recent years, they have developed faster, cheaper, and more precise methods to add, remove, or change genes in living organisms. Researchers are working to develop therapies that use gene editing to treat children or adults for a range of conditions, including sickle cell, hemophilia, and some forms of cancer and blindness.

Since 2015, a few laboratories have been experimenting with a far more controversial use of CRISPR: editing the genomes of early human embryos, eggs, and sperm. If edited embryos are used to start a pregnancy, the changes affect every cell in the body of any resulting child, that child’s offspring, their offspring, and so on. Dozens of countries already prohibit any attempt to start a pregnancy with edited embryos, yet some scientists seem eager to proceed.

In November 2018, researcher He Jiankui from Shenzhen, China announced the birth of the first gene-edited babies: twin girls publicly referred to as Lulu and Nana. In a reckless and widely condemned experiment, He had edited the DNA of two embryos and used them to start a pregnancy. The babies were born prematurely and their current health status is unknown.

These utterly unethical experiments have pushed the issue of human genome editing to the forefront of media, scientific, and public discussion and debate. Any discussion of how we might use this technology in the future needs to consider the serious societal consequences of human genome editing. This includes examining the rise of vast economic inequalities and the resurgence of overt xenophobia and racism in many parts of the world. It also includes acknowledging our eugenic histories and the present-day systemic oppression of women, people of color, Indigenous people, LGBTQ people, and people with disabilities, particularly as they relate to reproduction and ideas about who is “fit” to reproduce.

Human genome editing is not just a scientific issue. It is a political and social justice issue that intersects with the concerns of multiple movements, including disability rights, LGBTQ rights, reproductive rights and justice, racial justice, environmental justice, and health justice. Read on to learn more about human genome editing and why everyone should have a say in the decisions we make about whether and how to use this powerful technology.

What is CRISPR?

CRISPR is a gene editing technology that allows scientists to make changes to the DNA of living organisms more precisely and inexpensively than before. CRISPR stands for clustered regularly interspaced palindromic repeats. These segments of DNA occur naturally in bacteria, where they store information that helps recognize invading viruses. Associated enzymes, such as Cas9, then cut viral DNA out of the bacterial genes.

Scientists discovered that they can adapt CRISPR-Cas molecules to search for a specific DNA sequence and cut precisely at that point — not just in bacteria, but in plant, animal, and human cells, too. They can also provide a new DNA sequence for the cell to use when it repairs the cut.

CRISPR-Cas is often compared to the “find and replace” function in a word processor, but this metaphor of gene “editing” can make it sound more precise than it actually is. CRISPR sometimes mis-recognizes a DNA sequence that is similar to the one it’s looking for and cuts in the wrong place, causing “off-target mutations.” Other times it might cut in the right place, but cause mistakes, or “indels,” where DNA is incorrectly inserted or deleted.

Gene Therapy: Changing genomes to treat disease

There are two distinct ways gene editing might be used in humans. Gene therapy, or somatic gene editing, changes the DNA in cells of an adult or child to treat disease, or even to try to enhance that person in some way. The changes made in these somatic (or body) cells would be permanent but would only affect the person treated. One way this is already being done is by editing a person’s immune cells to help them better fight cancer. Clinical trials will soon be underway to use CRISPR to edit blood cells as a treatment for sickle cell anemia and other blood disorders. Gene therapy raises many of the same social and ethical issues as other high-tech medical treatments, including ethical research practices, safety and effectiveness, unequal access to expensive treatments, and how we allocate resources, but is widely supported as a promising way to treat disease.

Germline Editing: Changing the genomes of future generations

But there is a much more controversial way that human gene editing could be used. In germline modification, gene editing would change the DNA of embryos, eggs, or sperm. Because germline DNA is passed down to all future generations, any changes — whether they had beneficial or harmful effects — would be as well. Some have proposed that germline editing could be used to prevent inherited diseases, but this would carry unacceptably serious safety, ethical, and social risks. And it’s unneeded, since we already have safe and effective ways to prevent passing on an inherited disease. People at risk can use preimplantation genetic diagnosis (PGD), a way to screen embryos created through in vitro fertilization (IVF) and select one that is unaffected this allows parents to have a genetically related child without passing on an inherited disease. PGD certainly raises its own ethical questions, particularly around disability rights and justice, but it poses fewer safety and societal risks than germline editing would.

Understanding the Social and Ethical Risks

New technologies often raise ethical questions about their unknown risks and benefits. These questions become especially tricky — and essential — when we are talking about something like human germline editing, which affects future generations who obviously can’t consent to the changes being made to their DNA. What risks would women (who are rarely mentioned in discussions about human gene editing for reproduction) be subject to as the ones who would carry pregnancies started with genetically modified embryos and deliver the resulting children (for themselves or for others)? How could potential parents make informed decisions when there would be unknown health risks that might emerge during pregnancy for the woman and the fetus, epigenetic effects, and health issues that might not develop until adulthood or old age (or even in future generations)? It would be extremely difficult, if not impossible, to ethically conduct the kind of follow-up studies that would be necessary to say that human genome editing is safe enough to use in reproduction.

But focusing on these obvious safety risks takes too narrow a view and overlooks the many serious social and ethical risks that germline editing would pose. Imagine wealthy parents being able to purchase enhancements (real or perceived) for their children, and the kind of world that would result if children’s education and life chances were thought to be determined at birth by their DNA. Imagine the long-term consequences of imposing the preferences and biases we hold today on the genes of all future generations. Consider the potential effects on groups that have less power in society and are already discriminated against, including people with disabilities, people of color, and women. Ableism, racism, and reproductive injustices would likely be exacerbated by human genome modification, if it were ever allowed. These and other social inequalities that already shape our lives could rapidly grow worse, and new forms of inequality could be introduced, leading to a new form of eugenics.

While it might seem possible to avoid such dire outcomes by limiting the use of germline gene editing to the prevention of serious diseases, this would be extremely difficult. The line between therapy and enhancement is fuzzy and would be nearly impossible to enforce. How would we determine which diseases are serious enough to edit out? And who would decide? There are many disabled people who value their differences as a form of human diversity and do not think they need to be “treated” or “cured.” Allowing just some uses of germline gene editing for reproduction would mean opening the door to all uses. For these reasons, over 40 countries have banned human germline modification.

Who Gets to Decide?

Human germline editing is not just a scientific or technical issue. It affects how we understand ourselves as humans and what kind of future we want to build. It has implications for society as a whole, not just individuals. Therefore, decisions about whether to permit germline modification should not be made by small groups of scientists or bioethicists, by biotechnology companies, or by wealthy elites. Human germline editing is an urgent social justice issue we need public discussions of it that are open to all.


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