Tag Archives: gene-editing

How CRISPR-Cas9 gene editing is set to change the world

CRISPR is a highly precise new method of gene-editing. Image credits: National Human Genome Research Institute

From The Island of Dr. Moreau to Bladerunner to Gattaca, the world of sci-fi on the silver screen has had a long interest in genetic manipulation. Films such as these often portray gene editing as the next big Frankenstein’s monster of biology, which is hardly a positive portrayal. Moreover, it isn’t an accurate one. The world of gene editing is a lot more complex than that.

What’s more, it’s not just sci-fi; gene editing is quickly becoming a reality. It’s too late to put the genie back into the bottle. That’s due in no small part to the fact that gene editing is a lot more accessible today than in decades past. As such, even if some countries decided to pass bans against the practice, others could continue ahead apace, creating an unequal scientific playing field on the subject of genetics.

Today, accessibility and gene editing often mean one tool in particular — CRISPR. Written in full, the tool is called Clustered Regularly Interspaced Short Palindromic Repeats. This almost certainly doesn’t clear up for you what this actually is or does, however, so let’s take a closer look at one of the leading gene editing tools in the toolbox and how it can be put to work to benefit us.

CRISPR 101

For those not in the know, CRISPR is a gene-editing tool that is developed from a natural means by which microbial bacteria edit out pieces of DNA. When a virus infects bacteria, it injects DNA or RNA into the cell, which responds by releasing a form of nuclease (Cas9) to take a snippet of the DNA or RNA sequence and store something equivalent to a genetic memory of the infection. That way, the cell has a memory of and thus a defense against infection from such a virus in the future.

The type of CRISPR we employ works in a similar fashion, snipping out DNA and RNA strands that we wish to use for a given purpose and replacing them with a DNA strand that we would prefer to have in its place. Imagine DNA to be a series of multi-colored Lego bricks. CRISPR-Cas9 thus essentially works by identifying the sequence of colored Legos that we’d want to replace, breaking them off, and replacing them with new bricks.

CRISPR and Gene Therapy

Why do this?

Think of all the diseases that exist due to faulty or damaged DNA. With a technique such as CRISPR gene editing, and the almost infinite choice of Crispr-Cas9 lentivirus vectors, we could in theory snip out the damaged or dangerous DNA strands and replace them with “healthy” sequences.”

Consider horrible and currently incurable diseases such as forms of cancer and Huntington’s disease. We could, in theory, snip out the parts of DNA sequences that code for many horrible conditions, such as sickle cell disease, and replace them with “healthy” substitutes, thereby dramatically improving the condition of or even potentially curing the patient. 

CRISPR for Plants and Animals

There are other benefits that can come from CRISPR as well, not the least of which being work that can be done with animals. Genetic manipulation of animals has already gone on for decades, perhaps millennia if you include the way in which we as human beings have domesticated and bred animals to suit our needs. Modern genetic engineering has taken that focus on animal breeding and “improvement” to a whole new level.

Instead of simply breeding semi-blindly and hoping that we get a good result from animals that display positive genetic traits that we wish to emphasize, we can simply cut into their DNA sequences and insert samples of that species’ DNA that codes for traits we like. The same can be done with plants.

On one hand, that’s certainly a bit close to playing Dr. Frankenstein with nature.

On the other hand, that’s also a potential way to breed more and larger food and this can be a huge game-changer in the fight against world hunger.

That’s because CRISPR is, at the end of the day, a tool with its ultimate nature determined by how we use it. Shelley’s Victor Frankenstein seeks to play God and conquer “life and death,” imagining himself as being by his creations as the “creator and source” of a new species. At its noblest, CRISPR isn’t about playing God with different species but rather helping improve the life of our own.

Credit: Pixabay.

Chinese researchers breed smarter monkeys after inserting human brain gene

Scientists in China have inserted a human gene that plays an important role in our brain’s development into the genome of macaque monkeys. Some of the monkeys that were bred in this manner exhibited improved cognitive function. However, the international community has condemned the experiment as unethical.

Credit: Pixabay.

Credit: Pixabay.

The research led by scientists at the Kunming Institute of Zoology in southwestern China involved inserting human copies of the MCPH1 gene into monkey embryos via a virus that carried the gene. A total of 11 transgenic macaque monkey embryos were generated, out of which only five survived. These surviving monkeys were put through a barrage of cognitive tests, including memory tests and brain scans. The results suggest that the macaques performed better on short-term memory tasks than their unmodified peers and their brains developed over a longer period of time, which is typical of human development.

According to the researchers, the aim of the study is to probe the fundamental biology that enabled humans to develop our unique brand of intelligence. So, naturally, the Chinese authors decided to zero-in on a gene that is involved in brain size and cognitive abilities. In the future, similar research might enable scientists to develop treatments for diseases caused by abnormal brain development. For instance, over the years, Chinese researchers have engineered monkeys that show signs of Parkinson’s, Duchenne muscular dystrophy, autism, and more.

Another gene that may be soon be added inside the monkeys of genomes in subsequent experiments is FOXP2, which is widely believed to be integral to our language abilities. Then there’s SRGAP2C, a gene variant that first appeared around two million years ago as one of our ancestors, Australopithecus, was losing ground in Africa to early humans. This gene is also called “humanity’s switch” due to its alleged role in the emergence of human intelligence.

While such scientific inquiries definitely have their merit, their ethics are controversial. Su Bing, from the Chinese Academy of Sciences’ Kunming Institute of Zoology and lead researcher of the new study, says that the experiments were validated by the institution’s ethics board and followed Chinese and international best practices.

Other voices in the scientific community, however, disagree. Critics believe that transgenic experiments on monkeys and apes puts us on a slippery slope where it becomes difficult to draw the line of what is acceptable and what is not. One such critic is University of Colorado geneticist James Sikela who wrote a 2010 paper arguing that transgenic experimentation on primates raises a number of ethical problems, as well as physical harm.

“Transgenic apes, our closest evolutionary relative, have the highest potential to express human lineage specific (HLS) sequences as they are expressed in Homo sapiens and likewise experience harm from such transgenic research. These harms render the conduct of this research ethically unacceptable in apes, justifying regulatory barriers between these species and all other non-human primates for transgenic research,” Sikela and colleagues wrote at the time.

Animals are regularly inflicted with various diseases so that scientists can then experiment on them to find new treatments and drugs. Changing an animal’s genome, however, is completely different in the sense that it can alter its fundamental biology. Critics argue that humans and macaque monkeys are different on many levels and that simply modifying a couple of genes offers little value. For instance, this study’s small sample size means that researchers can’t conclude with confidence that the introduced gene variant made the animals smarter, nor does the study tell us anything new about the MCPH1 gene.

Writing for MIT Technology Review, University of Colorado bioethicist Jacqueline Glover compared the new study from China to something out of the Planet of the Apes, a movie where enhanced primates overthrow humans.

“You just go to the Planet of the Apes immediately in the popular imagination,” she said. “To humanize them is to cause harm. Where would they live and what would they do? Do not create a being that can’t have a meaningful life in any context.”

This is just the most recent research out of a string of controversies stemming out of Chinese labs. Last year, He Jiankui and colleagues at the Southern University of Science and Technology, in Shenzhen, shocked the world after announcing the first gene-edited babies. In the future, we’ll likely be surprised by even more outlandish findings.

Credit: Wikimedia Commons.

Scientists treat first US patients with gene-edited cells

Credit: Wikimedia Commons.

Credit: Wikimedia Commons.

CRISPR-cas9, the powerful gene-editing tool, has been getting a bad reputation lately following last year’s shocking news of Chinese twins born with altered genomes. But done diligently and ethically, CRISPR holds the promise to treat some of the most gruesome diseases. At the University of Pennsylvania, scientists have used this technology to make precise DNA modifications to the immune cells of two cancer patients. The ongoing trial marks the first time that CRISPR has been used to treat patients on US soil.

One of the patients has myeloma, and the other one has sarcoma. Both didn’t respond to standard treatment, which is why they agreed to participate in an experimental trial.

CRISPR-Cas9 allows scientists to alter the DNA of different organisms with high speed and precision. It essentially works by injecting a living organism with a DNA construct composed of the Cas9 enzyme that cuts or deletes a segment of DNA, a sequence of RNA that guides the Cas9 to the correct location to cut, and a new DNA template that repairs the cut and alters the gene. Before CRISPR entered the picture, gene editing was a time-consuming and laborious procedure that often ended in failure.

The ongoing trial involves extracting immune system cells, known as T cells, from the blood of the patients, then genetically modifying these cells. The plan is to remove three of the cells’ receptors and to add a gene for a receptor called NY-ESO-1, which is a protein that appears on the surface of some cancers. The modified cells would then be infused into the bodies of the cancer patients after they had received a brief course of chemotherapy.

Ultimately, the researchers hope that the modified cells will target and destroy the cancer cells. So far, no other information has been released to the public but we know that the study will eventually include a total of 18 patients.

Unlike the reckless Chinese experiment that edited the genes of human embryos, the trial involves altering the DNA of individual patients. This means that these modifications will not be passed down the germline so there is no danger of re-engineering the entire human species. Gene-editing of heritable traits is not allowed in the United States and in many other countries.

Besides this trial, a number of research institutes have started or are preparing to start their own CRISPR trials on human patients this year. NPR informs that two trials are underway meant to treat genetic blood disorders, such as sickle cell disease and beta-thalassemia. Another study wants to use CRISPR to treat an inherited form of blindness known as Leber congenital amaurosis. Several other cancer studies are due to kick off this year in Texas, New York and elsewhere.

All of these studies are extremely experimental and the patients involved in them face considerable risks. The biggest concern is that these therapies might cause unintended changes in DNA that could lead to health problems. And even if these preliminary trials are deemed successful, it might take many years before the public gains access to them.

A new technique uses nanoparticles to deliver genes into the chloroplasts of plant cells, works with many different plant species. Credit: MIT.

Nanoparticles inject genes directly into the chloroplast of plants

A new technique uses nanoparticles to deliver genes into the chloroplasts of plant cells, works with many different plant species. Credit: MIT.

A new technique uses nanoparticles to deliver genes into the chloroplasts of plant cells, works with many different plant species. Credit: MIT.

Researchers at MIT sprayed tiny nanoparticles containing foreign genes into the chloroplasts of plant cells. The novel technique is an easier and less risky way to genetically modify plants, in contrast to established gene tools which can be expensive and cumbersome.

DNA delivery straight to the plant’s cell

The researchers, led by Michael Strano, who is a professor of chemical engineering at MIT, first learned that they could penetrate plant cell membranes with nanoparticles a few years ago. At the time, they found that if the size and electrical charge of the nanoparticles were just right — and every plant is different — they could then penetrate the plant cell’s membrane through a mechanism called lipid exchange envelope penetration (LEEP).

Previously, Strano and colleagues used this method to make plants grow by embedding luciferase, a light-emitting protein, into the leaves of a plant. But could genes be implanted in the same way? That’s what the research team set out to discover in their latest study published in Nature Nanotechnology.

“Bringing genetic tools to different parts of the plant is something that plant biologists are very interested in,” Strano says. “Every time I give a talk to a plant biology community, they ask if you could use this technique to deliver genes to the chloroplast.”

Chloroplasts are small organelles inside the cells of plants and algae, where sugar is made for fuel through photosynthesis. These tiny organelles contain about 80 genes, which code for proteins involved in photosynthesis.

Scientists had previously manipulated genes inside chloroplasts using a high-pressure technique called “gene gun”, however, this can result in damage to the plant and is not very effective.

First, the MIT researchers created nanoparticles consisting of carbon nanotubes wrapped in chitosan, which a naturally occurring sugar. They then added DNA whose negative charge allows it to easily bind to the positively charged nanotubes. The nanoparticle solution is then simply sprayed with a needleless syringe onto leaves, penetrating them through tiny pores called stomata, which typically regulate water evaporation.

The nanoparticles pass through the cell’s wall, membrane, ultimately penetrating the double membranes of the chloroplasts. Once inside, the slightly less acidic environment of the chloroplast causes the DNA to disentangle from the nanoparticles, which is now free to produce proteins.

As a demonstration, researchers used this technique to deliver a gene that codes for a yellow fluorescent protein in order to easily visualize the effectiveness of the process. They found that 47% of plant cells glowed in yellow, showing that the DNA producing the protein had been successfully delivered to the chloroplast. Researchers employed a variety of plants, including spinach, watercress, tobacco, arugula, and Arabidopsis thaliana. Virtually any kind of plant, including food crops, can be used. What’s more, different kinds of nanomaterials other than carbon nanotubes ought to work to produce similar results.

“This is a universal mechanism that works across plant species,” Strano said.

The technique could prove useful in engineering crops and vegetables with useful traits, such as drought and fungal resistance. And because the genes are carried only in the chloroplasts, they are only passed to offspring and not other plant species.

“That’s a big advantage, because if the pollen has a genetic modification, it can spread to weeds and you can make weeds that are resistant to herbicides and pesticides. Because the chloroplast is passed on maternally, it’s not passed through the pollen and there’s a higher level of gene containment,” Tedrick Thomas Salim Lew,  MIT graduate student and co-author of the study, said.

He Jiankui. Credit: Wikimedia Commons.

The rogue Chinese scientist who made the first gene-edited human babies could face death penalty

He Jiankui. Credit: Wikimedia Commons.

He Jiankui. Credit: Wikimedia Commons.

He Jiankui, the controversial scientist whose unlicensed work led to the birth of twin baby girls whose DNA was modified, is in big trouble. Since his announcement sparked international outcry, the Chinese scientist has come off the radar. According to sources close to the matter, He Jiankui has been under armed guard at a state-owned apartment in Shenzen, China, since early December. The scientist is now facing corruption and bribery charges, both crimes that carry the death penalty in China.

A scapegoat?

The Chinese researcher, who used to be an Associate Professor at Southern University of Science and Technology, in Shenzhen, used CRISPR gene-editing technology to modify live embryos. The procedure allegedly modified the CCR5 gene in such a way as to potentially make the offspring resistant to HIV. Instead of destroying the embryos, per research guidelines in China, He Jiankui and associates planted the embryos in surrogate mothers and allowed the pregnancy to follow through, resulting in the birth of twin baby girls. The birth has not been independently confirmed or documented in a peer-reviewed journal, but respectable researchers with access to some of He’s work say in all probability the work was carried through

The announcement was made quite nonchalantly by He during a keynote presentation at the Second International Summit on Human Genome Editing at the University of Hong Kong, held in November 2018. One of the organizers, geneticist Robin Lovell-Badge of the Francis Crick Institute in London, had invited He to speak at the conference after learning of his plans. Lovell-Badge had hoped that attending the conference with some of the foremost people in the field would temper the Chinese scientist’s enthusiasm. But much like everybody else at the event, Lovell-Badge was flabbergasted to learn that He wasn’t just planning — the work had already been done.

“None of us knew how far he’d actually got,” Lovell-Badge said, adding that experts knew only of his research on mice, monkeys and human embryos. “Clearly, we were too late.”

Subsequently, we came to learn that He had been working on his research while on unpaid leave and used his own financial resources to hire people to help him. He had founded and sold various companies which made him very wealthy and respected (until recently) by Chinese elites. Although the documents the Chinese researchers filed for clinical trials included a valid ethical review, the hospital involved denied that its ethics review committee ever met to discuss the work. China’s Southern University, where He and colleagues were employed, said it did not support the experiment. The university also announced that it has launched an investigation. To make matters worse, He is a trained physicist with little to any experience in biology.

What’s striking is that the 34-year-old scientist had no sense of remorse while making his ‘big’ announcement in Hong Kong. He actually said that he was proud of the achievement.

Well, it seems that Chinese authorities are of a different opinion.

Speaking to The Telegraph, Lovell-Badge said He could face corruption and bribery charges, adding that “quite a few people have lost their heads for corruption.” Indeed, things look pretty gloomy for He Jiankui, who was expecting reverence as a pioneer, but who instead could face the axe.

“Lots of people are probably going to lose their jobs, he wasn’t the only one involved in this obviously. So how has he got them to do all this work? He could be had up on all sorts of charges of corruption and being guilty of corruption in China these days is not something you want to be,” Lovell-Badge told The Telegraph.

“Here you have a physicist who knows little biology, is very rich, has a huge ego, wants to be the first at doing something that will change the world,” Lovell-Badge added.

Lovell-Badge says that He is currently confined to an apartment under armed guard. It’s not clear at this point if the guards are there to restrict him or protect him. Since He made his controversial announcement, the Chinese physicist has received many death threats.

For the moment, He is under investigation by the Chinese government and could face jail time or even the death penalty, in the most extreme case. It’s an incredibly opaque situation at this point, as with many dark things in China. It would be very convenient for the local authorities to present a scapegoat — the head on a pike that eases the anger of the masses. However, what’s to keep something similar from happening again? If there’s anything to learn from this whole scandal it is that all countries should require stricter oversight and laws around gene editing on humans.

Left: Modified tobacco plant with 40% more biomass thanks to photorespiration shortuct. Right: much smaller unmodified tobacco plant. Credit: RIPE.

Photosynthesis genetic shortcut makes crops 40% more productive

Left: Modified tobacco plant with 40% more biomass thanks to photorespiration shortuct. Right: much smaller unmodified tobacco plant. Credit: RIPE.

Left: Modified tobacco plant with 40% more biomass thanks to photorespiration shortuct. Right: much smaller unmodified tobacco plant. Credit: RIPE.

The world’s population is not only growing in absolute numbers, but also in its wants and needs. Rightfully so, people desire access to calorie-rich, healthy, nutritious food — but all of this puts incredible strain on our water and land resources, as well as on our carbon budget. One solution is growing more food with the same resources by engineering crops to yield more per acre. The latest contribution towards this goal involved engineering crops with a photorespiratory shortcut, which led to a 40% increase in yield in real-world conditions.

Taxing breathing

The backbone of photosynthesis — the process used by plants and other organisms to convert light energy into chemical energy — is an enzyme called Rubisco. However, the most abundant protein on Earth has been a bit too successful for its own good, having contributed to a much more oxygen-rich atmosphere compared to the time the enzyme first evolved. The immediate consequence is that Rubisco is not always able to distinguish between carbon dioxide — which it uses along with water to promote plant growth — and oxygen, which is a byproduct of photosynthesis but also toxic to plants. Plants act on oxygen instead of carbon dioxide about 20% of the time.

In order to adapt, plants have developed a process called photorespiration. For most plants, this metabolic pathway is wasteful, expending a lot of energy and interfering with photosynthesis.

“Photorespiration is anti-photosynthesis,” lead author Paul South, a research molecular biologist with the Agricultural Research Service, said in a statement. “It costs the plant precious energy and resources that it could have invested in photosynthesis to produce more growth and yield.”

South and colleagues part of the Realizing Increased Photosynthetic Efficiency (RIPE), an international research project whose mission is to engineer crops with more efficient photosynthesis, sought to simplify photorespiration in order to cut its energy use. Normally, photorespiration uses three compartments in the plant’s cell that are joined together through a complex route. To optimize the pathway, the researchers tweaked different promoters and genes, creating three alternate routes.

Modified tobacco (left) vs unmodified plant (right). Credit: RIPE.

Modified tobacco (left) vs unmodified plant (right). Credit: RIPE.

Over the course of two years, the research team tested these roadmaps in 1,700 plants until they found the most optimized version. The study only involved tobacco plants, a model organism in genetic studies because it is easier to engineer. The modifications can be applied to any other photosynthetic plant, nevertheless.

The researchers found that the engineered tobacco grew faster, taller, and produced 40% more biomass than unmodified plants. Unlike previous photorespiration studies, South and colleagues tested their work in the field, in real-world agronomic conditions.

It might take another decade, however, before the biotech can be applied at scale to food crops and achieves regulatory approval. Meanwhile, the researchers are performing greenhouse experiments with modified potatoes, and plan on doing similar tests with soybean and rice.

“We could feed up to 200 million additional people with the calories lost to photorespiration in the Midwestern U.S. each year,” said principal investigator Donald Ort, a professor of Plant Science and Crop Sciences at Illinois’ Carl R. Woese Institute for Genomic Biology. “Reclaiming even a portion of these calories across the world would go a long way to meeting the 21st Century’s rapidly expanding food demands—driven by population growth and more affluent high-calorie diets.”

The findings were reported in the journal Science. 

He Jiankui is a Chinese biomedical researcher, who was trained in the United States. He became widely known in November 2018 after he said that he had generated the first human genetically edited babies, Lulu and Nana. Credit: Wikimedia Commons.

China pulls the plug on rogue scientist who genetically modified twin human babies

He Jiankui is a Chinese biomedical researcher, who was trained in the United States. He became widely known in November 2018 after he said that he had generated the first human genetically edited babies, Lulu and Nana. Credit: Wikimedia Commons.

He Jiankui is a Chinese biomedical researcher, who was trained in the United States. He became widely known in November 2018 after he said that he had generated the first human genetically edited babies, Lulu and Nana. Credit: Wikimedia Commons.

Everyone was completely taken by surprise when, earlier this week, a Chinese scientist announced that he had used gene-editing technology to alter the genes of twin girls. The lack of transparency and gross lack of oversight, ethical or otherwise, attracted widespread international scrutiny. Today, the Chinese government announced that it had ordered a temporary halt on research for all personnel involved with the controversial gene-editing technique.

No shame, no remorse

He Jiankui, an Associate Professor at Southern University of Science and Technology, in Shenzhen, had announced that twin baby girls born this month had their embryonic genes edited using CRISPR technology. The Chinese researchers modified the CCR5 gene in such a way as to potentially make the offspring resistant to HIV.

The major concern is that any edits will be passed onto offspring, thus making their way into the gene pool. As such, potentially troublesome mutations could become relatively widespread. On the other hand, even if the gene editing process is flawless, any beneficial gene edits — such as enhanced resistance to disease and even intelligence — could result in unfair advantages and may open the door for eugenic practices.

“If true, this experiment is monstrous,” said Julian Savulescu, a professor of practical ethics at the University of Oxford. “The embryos were healthy. No known diseases. Gene editing itself is experimental and is still associated with off-target mutations, capable of causing genetic problems early and later in life, including the development of cancer.”

“There are many effective ways to prevent HIV in healthy individuals: for example, protected sex. And there are effective treatments if one does contract it. This experiment exposes healthy normal children to risks of gene editing for no real necessary benefit. In many other places in the world, this would be illegal punishable by imprisonment.”

Germline gene editing is banned in many countries. However, while it is not allowed per se, China does not stipulate any punishments for the practice.

Few people were aware that such work was being practiced, which certainly didn’t help calm down the scientific community. Some people hoped that He hadn’t really messed with the genomes of live human babies, since the research was not independently verified by a third party or peer-reviewed. However, all signs point to the fact that the procedure was indeed carried out. On Wednesday, He presented his work in great detail at the Second International Summit on Human Genome Editing in Hong Kong. At the end of the presentation, He stated he was proud of what he had done.

Speaking to New Scientist, Helen O’Neill, a CRISPR specialist at the University College London who attended the conference, said that the Chinese researchers really did it.

“Among the scientific community, we’re very sure. He gave quite an impressive presentation on quite extensive and thorough research that he had done both in animal and human embryos. The initial shock meant people went “Surely not – he has to prove it.” But I never had any doubt,” she said.

There are a number of very odd things about this whole affair. He has been off the radar for months, working on his research while on unpaid leave. Although the documents the Chinese researchers filed for clinical trials included a valid ethical review, the hospital involved denied that its ethics review committee ever met to discuss the work. China’s Southern University, where He and colleagues are employed, said it did not support the experiment. The university also announced that it has launched an investigation.

“The research work was carried out outside the school by Associate Professor He Jiankui. He did not report to the school and the department of biology, and the school and the biology department did not know about it,” a spokesperson from the university said in a statement.

The backlash following the most controversial (and some would say scandalous) research of the year was extremely intense. Following international outcry, the Health Ministry, Science and Technology Ministry and China Association for Science and Technology stated that “relevant bodies have been ordered to temporarily halt the scientific research activities of relevant personnel.”

The organizers of a conference where He announced the live gene editing also condemned the work, calling it “deeply disturbing” and “irresponsible.”

“Even if the modifications are verified, the procedure was irresponsible and failed to conform with international norms,” read a statement from the Second International Summit on Human Genome Editing,

These sentiments were shared by colleagues in the United States.

“The events in Hong Kong this week clearly demonstrate the need for us to develop more specific standards and principles that can be agreed upon by the international scientific community,” U.S. National Academy of Sciences (NAS) president Marcia McNutt and  U.S. National Academy of Medicine (NAM) president Victor Dzau said in a joint statement.

What’s shocking is that the twin baby girls will not be alone. Very casually, He announced during a Q&A at his keynote at this week’s Hong Kong conference that another CRISPR pregnancy is underway.

No one knows what will happen next. It’s simply unprecedented to have so many written and unwritten rules broken repeatedly. One thing’s for sure, all of this shaping up to be a huge disaster. He’s career looks like it’s going down the drain — but that should be the least of anyone’s worry. The real challenge now is preventing a biological meltdown and making sure nothing so reckless is allowed to ever happen again.

Ground cherry

In a just a few years, scientists could domesticate the delicious ground cherry

Move over, strawberry — there’s a new berry in town that Millenials are drooling over. Using state-of-the-art gene editing, researchers claim they’ve come close to domesticating the groundcherry, a wild berry native to Central and South America. Instead of waiting for decades or even thousands of years to domesticate the berry through conventional methods, the scientists say that their approach could bring this highly-sought-after food to supermarket shelves around the world much faster.

Ground cherry

Credit: Pixabay.

The ground cherry (Physalis pruinosa) is classed as an orphan crop — minor crops, which also includes tef, finger millet, yam, roots, and tubers, that tend to be regionally important but not traded around the world. The reason why such foods are rarely traded internationally is due to their poor shelf life and low productivity.

Sometimes called cape gooseberries, winter cherries, or husk tomatoes, ground cherries are small yellow fruits with a papery husk. Their taste has been described as something between a tomato and pineapple, which makes them great as ingredients in desserts, salads, jams, or even plain.

Ground cherries sometimes make their way into U.S. farmers markets where they sell like hotcakes. In order to make them more available to consumers, the orphan crop would have to be grown more easily and with a much higher yield. Typically, we’d have to wait for many years to completely domesticate the plant. However, researchers at the Boyce Thompson Institute decided to take a shortcut.

Researchers managed to bring the ground cherry from almost wild to almost domesticated in a matter of years. Credit: Sebastian Soyk.

Researchers managed to bring the ground cherry from almost wild to almost domesticated in a matter of years. Credit: Sebastian Soyk.

The team wanted to make the plant’s weedy shape more compact, give it larger fruits and more prolific flowers. First, they sequenced the ground cherry’s genome, which enabled them to identify the genes responsible for the crop’s undesirable traits. Then, the researchers used the controversial gene editing tool CRISPR to manipulate these target genes.

“I firmly believe that with the right approach, the groundcherry could become a major berry crop,” said Zachary Lippman, a plant scientist at Cold Spring Harbor Laboratory.

“I think we’re now at a place where the technology allows us to reach.”

Previously, the team manipulated the genomes of certain tomatoes — an approach which they applied to the ground cherry as well.

For now, the project is a proof of concept — the first orphan crop in which CRISPR was applied to make it a ‘family’ crop that has a high yield. In the future, the researchers plan on fine-tuning their method to improve desired characteristics, such as fruit color and flavor. Of course, some conventional plant breeding will be required in order to make the ground cherry mainstream. How long this will take is not clear, as there is also the issue of navigating CRISPR’s intellectual property rights.

In any event, Lippman says that the study is all about “demonstrating what’s possible”, such that other researchers might be inspired to take on other orphan crops that have the potential for rapid domestication. This way, food security will be improved and our plates can be enriched with new flavors and tastes.

The findings appeared in the journal Nature Plants.

gene puzzle

New CRISPR tools target RNA rather than DNA. They could fix ‘typos’ responsible for half of all genetic diseases

CRISPR-Cas9 technology revolutionized gene editing, enabling scientists to edit parts of the genome by removing, adding or altering sections of the DNA sequence. Since the tool was first mentioned in 2002, over 4,800 articles employing CRISPR appeared PubMed, with exponential adoption rates over the last three years. But CRISPR isn’t perfect and due to so-called ‘off-target effects’, the approach can sometimes cause undesirable mutations. You never want to hear ‘Oops!’ when altering DNA. Now, two new studies have tuned gene editing up a notch by enabling scientists to target and change a single letter in a string of DNA bases. No molecular scissors required.

gene puzzle

Credit: Pixabay.

Instead of slicing through the two spiraled strands of bases — the famous DNA double-helix — American researchers at the Broad Institute and MIT, on one hand, and at Harvard University, on the other hand, targeted DNA’s close chemical cousin: RNA. The two are different both structurally and functionally. DNA, for instance, is comprised of deoxyribose sugars rather than ribose sugars, as is the case of RNA. DNA is a sort of genetic blueprint responsible for storing and transferring genetic information. RNA, on the other hand, acts like a secondary copy which directly codes for individual amino acids. If they could precisely change individual letters in a RNA sequence, the scientists reckoned, then it would be possible to reverse disease-causing mutations.

Led by David Liu, the Harvard team presented a new gene editing technique called ‘base editing’ in the journal Nature. If CRISPR is like using a pair of molecular scissors to splice DNA and alter a genome, then base editing is like using a pencil and eraser, Liu says. In other words, this is a far sharper way of altering genomes in some applications. CRISPR will still have an important role to play for years to come.

The typo that can kill

The rules of base pairing (or nucleotide pairing) dictate that A (the purine adenine) always pairs up with T (the pyrimidine thymine) and C (the pyrimidine cytosine) always pairs with G (the purine guanine). What Liu and colleagues managed to do is they engineered an enzyme that targets the “A” base and changes it into a base called inosine, which is read as as guanine, the “G.” Then, the cell’s DNA repair machinery tries to ‘fix’ the complementary strand of DNA across the gap where the T is by inserting a C. What you eventually get is an A-T to G-C conversion.

This sort of letter switching happens all the time in nature and regularly cause disease in humans. A mutation from G to A, which is very common, has been implicated in cases of focal epilepsy, Duchenne muscular dystrophy, and Parkinson’s disease. According to Liu, about half of the 32,000 known pathogenic point mutations in humans can be traced down to mutations that change G-C to an A-T.

The second paper published in Science and authored by scientists at the Broad Institute and MIT took a different route for A-G conversion. They inserted a different adenosine deaminase enzyme into Crispr-Cas13, which is a variant genome editor that works on RNA. The enzyme used in this case, called PspCas13b, comes from the Prevotella bacteria and proved to be the most effective at inactivating RNA. The new CRISPR-based system is called RNA Editing for Programmable A to I Replacement, or “REPAIR.”

There are tens of thousands of human diseases that are caused by 'mistakes' in a single letter of DNA coding. Astoundingly, nearly early half could be fixed by changing an A to a G. (David Liu et al, Nature)

There are tens of thousands of human diseases that are caused by ‘mistakes’ in a single letter of DNA coding. Astoundingly, nearly early half could be fixed by changing an A to a G. (David Liu et al, Nature)

Senior author Feng Zhang says REPAIR has the ability to reverse the impact of any pathogenic G-to-A mutation regardless of its surrounding nucleotide sequence, with the potential to operate in any cell type. What’s more, the changes are reversible unlike the permanent alterations implied by DNA editing.

“REPAIR can fix mutations without tampering with the genome, and because RNA naturally degrades, it’s a potentially reversible fix,” explained co-first author David Cox, a graduate student in Zhang’s lab.

Both approaches provide a sharper and, most importantly, now reversible approach to gene editing. The main problem with CRISPR-Cas9 doesn’t lie in cutting but in the repair — the addition and tossing of bases which can sometimes lead to unwanted mutations. Operating on RNA, however, circumnavigates this issue because RNA repair doesn’t involve indels (stochastic insertions or deletions). With the scariest outcomes of CRISPR now potentially gone, gene therapy could grow immensely. Genetic diseases due to base defects could be eradicated and new classes of drugs could surface. Before that can happen, researchers need to find the best way to deliver the base editor machinery to the right tissues in the body and into the right cells. Scientists have a tremendous amount of work ahead of them but the future already looks intense.

“There’s immense natural diversity in these enzymes,” said co-first author Jonathan Gootenberg, a graduate student in both Zhang’s lab and the lab of Broad core institute member Aviv Regev. “We’re always looking to harness the power of nature to carry out these changes.”

A video shows the injection of gene-editing chemicals into a human egg near the moment of fertilization. The technique is designed to correct a genetic disorder from the father. Credit: MIT Tech Review.

Scientists edit the first human embryos in the United States

A video shows the injection of gene-editing chemicals into a human egg near the moment of fertilization. The technique is designed to correct a genetic disorder from the father. Credit: MIT Tech Review.

A video shows the injection of gene-editing chemicals into a human egg near the moment of fertilization. The technique is designed to correct a genetic disorder from the father. Credit: MIT Tech Review.

A team at the Oregon Health and Science University (OHSU) in Portland performed the first ever gene editing on a human embryo carried out inside the borders of the US. The researchers reportedly used CRISPR to edit portions of the genome where there were defective genes. These defects are known to cause inherited diseases in one-cell embryos.

Further than anyone has taken gene editing in the US so far

CRISPR-Cas9, the technique employed by the Oregon scientists, was invented a decade ago and makes gene editing incredibly easier and cheaper. Essentially, CRISPR acts like a molecular scissor of sorts that can be used to cut and paste portions of DNA. In early 2013,  researchers reported for the first time that they had used the CRISPR–Cas9 system to slice the genome in human cells at sites of their choosing. By 2014, 600 research papers mentioned it and now, a quick Google Scholar search reveals over 30,000 articles mentioning CRISPR, signaling the technique is rapidly becoming a mainstream scientific tool.

Of course, it’s not all fun and games with CRISPR. Such a powerful tool that acts on the blueprint of life — the genome — needs to be used with the utmost responsibility. One example of a safety concern is that a researcher created a virus with CRISPR-Cas9 that gave mice human lung cancer. A small mistake could work on human lungs also.

Previously, in 2015, Chinese researchers caused a lot of stir after they edited human embryos to remove a gene involved in the blood disorder beta-thalassemia. Then, in 2016, another group from China, which is the leading nation in CRISPR research, did something similar only this time the DNA was modified such that the embryo would be resistant to infection with HIV. However, the two attempts involved embryos fertilized by two sperm during in vitro fertilization (IVF), making them unviable past a certain post in their development.

CRISPR has been likened to a molecular scissor that can precisely cut portions of DNA. Credit: Science Mag.

CRISPR has been likened to a molecular scissor that can precisely cut portions of DNA. Credit: Science Mag.

The first CRISPR human trial started in October 2016 at the West China Hospital in Chengdu. Researchers harvested cells from a patient suffering from lung cancer and removed a gene called PD-1 — which cancer cells use to “trick” the body into not attacking them. The trial is set to end in 2018, so we’re still waiting for the results. And while most reports of CRISPR human gene editing came from China, it seems the United States is preparing to join ranks as well.

All previous trials involving genetically modifying human embryos had been blocked by Congress due to ethical concerns. One leading issue voiced in Congress is that allowing the practice would pave the way for so-called designer babies that are intentionally bred to have superior qualities. But in early 2017, the National Academy of Sciences released a report in which it endorsed human germline modification — altering an embryo with the intended purposes of eradicating a heritable disease. The reasoning is a child born out of that embryo will pass on these modifications with his or her germ cells, the egg or sperm.

“So far as I know this will be the first study reported in the U.S.,” Jun Wu, a collaborator at the Salk Institute, in La Jolla, California, who played a role in the project told MIT Tech Review. 

The embryos modified by the Oregon team led by Shoukhrat Mitalipov were never allowed to develop for more than a couple of days. They were also never meant to be implanted in any womb. Nevertheless, it was enough for the team to learn a great deal. For instance, previous attempts commanded by Chinese scientists caused editing errors in which DNA changes were only taken up by some cells in the modified embryo, but not all of them. This type of genetic error called ‘mosaicism’ wasn’t encountered during this study since their procedure also involved injecting CRISPR segments and sperm cells into the eggs at the same time.

For now, this trial is still pending publication so we’ll have to wait maybe a year before we learn more about the official results. In any case, we’re only beginning to scratch the surface with what gene editing can do. It’s exciting at the same time to witness first hand all of this play out. Designer babies or not, CRISPR is here to stay and what scientists will come up with might change humanity forever.

SafeGenes.

DARPA awards $65 million to make CRISPR safer, more efficient

The U.S. Defense Advanced Research Projects Agency (DARPA) has awarded a total of US$65 million to seven research teams aiming to improve CRISPR gene editing.

SafeGenes.

Image credits DARPA.

Their work will be the cornerstone of Safe Genes, a program which aims to “to gain a fundamental understanding of how gene editing technologies function; devise means to safely, responsibly, and predictably harness them for beneficial ends; and address potential health and security concerns related to their accidental or intentional misuse.”

Towards this end, each team will work on at least one of three areas of research:

  1. Developing genetic constructs to be used as cellular ‘instructions’. These should provide reversible control over genome editors in living cells and allow researchers to alter what they want whenever they want. In other words, goal #1 is to gain new and much more precise tools for genome editing.
  2. The development of drug-based countermeasures to provide preventive and treatment options which can limit genome editing in living organisms, or ensure genome integrity in populations of organisms. So goal #2 aims to ensure people and populations of organisms can be protected from unwanted genetic tampering.
  3. Finally, the teams will also be working on a way to eliminate engineered genes from a system to allow restoring them to their genetic baseline. Boiled down, #3 is the fail-safe — if something goes poorly, we’ll need something to use as a reset button.

The grantees include a team from the Harvard Medical School led by Prof. George Church, who believes editing tools that are even more accurate, easier and safer to use than CRISPR are possible in the near future.

His team plans to develop methods of detecting, preventing, even reversing mutations in genomes caused by exposure to radiation. They will also new computational and molecular tools that can distinguish between very similar areas of the genome and edit them with great accuracy. Finally, the team will also screen the effectiveness of drugs that inhibit gene editing activity.

Another of the grantees, a group headed by Amit Choudhary, Ph.D., will work on developing methods to control gene editing mechanisms in bacteria, mammals, and insects. They’re also interested in building a general platform for rapid and cheap identification of chemicals that will block contemporary and next-generation genome editors.

Such substances would allow gene editing to be used in therapeutic applications by limiting unwanted side-effects, or protect against biological threats. Finally, they’ll work on synthetic genome editors for precision genome engineering.

“Part of our challenge and commitment under Safe Genes is to make sense of the ethical implications of gene-editing technologies, understanding people’s concerns, and directing our research to proactively address them so that stakeholders are equipped with data to inform future choices,” said DARPA’s Safe Genes program manager Renee Wegrzyn.

“As with all powerful capabilities, society can and should weigh the risks and merits of responsibly using such tools. We believe that further research and development can inform that conversation by helping people to understand and shape what is possible, probable, and vulnerable with these technologies.”

It’s not fun and games with CRISPR: the technique can induce hundreds of unwanted mutations

As the revolutionary CRISPR gene editing technique promises to revolutionize the world, it’s important to also keep in mind the potential downfalls. A new study has revealed that the technique could introduce hundreds of unwanted mutations.

CRISPR-associated protein Cas9 (white) from Staphylococcus aureus based on Protein Database ID 5AXW. Credit: Thomas Splettstoesser (Wikipedia, CC BY-SA 4.0).

Clustered regularly interspaced short palindromic repeats (CRISPR) are segments of prokaryotic DNA containing short, repetitive base sequences which can be programmed to target specific stretches of genetic code, enabling us to edit DNA at precise locations. The method can be simplistically defined as a genetic scissor. CRISPR yields immense promise in gene editing and is almost set for clinical trials, but it’s not all easy-peasy, as a new study has revealed

“We feel it’s critical that the scientific community consider the potential hazards of all off-target mutations caused by CRISPR, including single nucleotide mutations and mutations in non-coding regions of the genome,” says co-author Stephen Tsang, MD, PhD, the Laszlo T. Bito Associate Professor of Ophthalmology and associate professor of pathology and cell biology at Columbia University Medical Center and in Columbia’s Institute of Genomic Medicine and the Institute of Human Nutrition.

The first clinical trial is slated to start this year in China, the next one is set for 2018 in the US. But even with the extreme precision of the technique, errors are still quite possible — even more so than we anticipated. Most studies that search for these missteps use predictive computer algorithms, but Tsang and his colleagues believe these models are often quite a bit off.

“These predictive algorithms seem to do a good job when CRISPR is performed in cells or tissues in a dish, but whole genome sequencing has not been employed to look for all off-target effects in living animals,” says co-author Alexander Bassuk, MD, PhD, professor of pediatrics at the University of Iowa.

To test their theory, they sequenced the entire genome of mice that had undergone CRISPR gene editing in one of their previous studies. In that study, CRISPR successfully corrected a gene that causes blindness, but now, they also found more than 1,500 single-nucleotide mutations and more than 100 larger deletions and insertions. Rather worryingly, none of these extra mutations weren’t predicted by the algorithms. Since even a single nucleotide being modified can cause significant problems, the effects of all these mutations together are virtually impossible to determine. But it might not be as bad as it looks.

For all these negative mutations… the mice seem to be fine and healthy. In fact, researchers say, this is no reason to scrap CRISPR or forego its advantages. Instead, Vinit Mahajan, associate professor of ophthalmology at Stanford University who was also involved in the study, is still a great supporter of CRISPR.

“We’re still upbeat about CRISPR,” says Dr. Mahajan. “We’re physicians, and we know that every new therapy has some potential side effects–but we need to be aware of what they are.”

However, even when the animals appear to be healthy and normal, scientists warn against putting all the eggs in the computer algorithm basket. They recommend using the full genome sequencing technique to complement the predictive algorithms and

 

The paper is named “Unexpected mutations after CRISPR-Cas9 editing in vivo.” Additional authors are Kellie A. Schafer (Stanford University), Wen-Hsuan Wu (Columbia University Medical Center), and Diana G. Colgan (Iowa).

 

HIV budding.

Scientists tie antibody escorts on white blood cells’ access points to stop HIV dead in its tracks

Researchers have developed a new technique that could provide long-term defense, possibly even a cure, for HIV patients. The method calls for HIV-antibodies to be anchored to immune cells, creating a population of resistant cells which can then take the fight to the virus.

HIV budding.

HIV budding (spherical growth on the left) in a cultured white blood cell.
Image credits C. Goldsmith / CDC.

Scientists at the Scripps Research Institute (TSRI) may have found a way to hit HIV where it hurts it the most — by taking away the virus’ ability to infect white blood cells. The work is remarkable for its shift in the way antibodies are deployed against HIV. Instead of launching a full-body (but low density) flood of antibodies which float freely in the bloodstream, TSRI researchers led by study senior author Richard Lerner, M.D., Lita Annenberg Hazen Professor of Immunochemistry at the institute, have developed a way in which antibodies can be piggybacked directly on white cells. These active compounds will be tied to the same receptors HIV uses to enter the cells, making out immune system finally immune from the dreaded virus.

“This protection would be long term,” said Jia Xie, senior staff scientist at TSRI and first author of the study.

It comes down to something Xie calls the “neighbor effect.” As the old adage goes, one antibody in hand is worth a hundred five capillaries away. Ok, I may have taken some liberty with that but the underlying idea is that concentrating antibodies to first and foremost defend white cells allows our bodies to join in on the fight — regular treatments can’t do that, and they’re left with a lonely uphill battle against HIV. Even worse, in case HIV is flushed out of the system but the patient gets infected again, his or her immune system will be just as abysmal at fighting off the virus.

Safety first, advances second

Before tailoring the technique against HIV, the team worked with rhinovirus (the bug responsible for most common colds) as a test subject. A lentivirus was used as a vector to deliver a set of genes to a culture of human cells, instructing them to manufacture antibodies and bind these to the receptor rhinovirus ties to (ICAM-1). The rhinovirus was then unleashed upon the culture, but with no access point inside the cells it shouldn’t infect most of them, the theory goes.

That ‘most’ is exactly why they didn’t start testing off the bat with HIV. Gene delivery systems are basically dumbed down viruses with edited genomes, which have to infect cells and paste their genetic data inside the host’s genome. But no system can reach all cells, so the culture became a mix of edited (immune) and non-edited (vulnerable) cells. The point of the experiment was to see how the colony as a whole would fare.

It actually went pretty good. There was an initial shock of about two days when the majority of cells died off. Control cultures, which held only unedited cells, never recovered after the infection. Mixed cultures, however, got back to about the same numbers as prior to infection after about 125 hours — only this time, they were all descendants of the most resistant cells. In essence, the team forced the cultures to go through an evolutionary crash course in the lab dish. All the vulnerable cells were consumed in the infection and the resistant cells multiplied and passed off their anti-rhinovirus genes along.

“This is really a form of cellular vaccination,” said Lerner.

HI virion structure.

The best thing about this study is that HIV is technically a lentivirus. Nothing beats a dash of irony to go with your scientific win.
Image credits Thomas Splettstoesser.

Next, they used the same system against HIV. The team tested a number of antibodies to find one which could protect the CD4 receptor (the one HIV uses) on immune cells, copied the corresponding genes in the lentivirus, then let them loose upon the culture. And again, it worked. They further showed that these tethered antibodies worked more efficiently at blocking HIV than free-floating antibodies in another experiment led by study co-authors Devin Sok of the International AIDS Vaccine Initiative (IAVI) and TSRI Professor Dennis Burton.

TSRI now plans to collaborate with researchers at City of Hope’s Center for Gene Therapy to get early efficiency and safety testing done prior to human trials, as per federal regulations.

“We at TSRI are honored to be able to collaborate with physicians and scientists at City of Hope, whose expertise in transplantation in HIV patients should hopefully allow this therapy to be used in people,” Lerner added.

The paper “Immunochemical engineering of cell surfaces to generate virus resistance” has been published in the journal Proceedings of the National Academy of Sciences.

An eight-cell embryo. Credit: Wikimedia Commons

Swedish scientists plan to edit the genes of healthy human embryos, treading on thin ice

An eight-cell embryo. Credit: Wikimedia Commons

An eight-cell embryo. Credit: Wikimedia Commons

Swedish biologist Fredrik Lanner and colleagues at the Karolinska Institute in Stockholm plan to edit healthy human embryo genes, marking a first in science if they become successful. The once edited human embryos will not be allowed to survive past 14 days and the stated goal is to learn about what genes are involved in miscarriages or infertility. Not everyone is convinced that this highly controversial study ought to be allowed to take place, though, as some fear it might create the necessary precedent for far more worrisome interventions like introducing genetically edited humans into the gene pool or so-called ‘designer babies’.

“Having children is one of the major drives for a lot of people,” Lanner told NPR. “For people who do struggle with this, it can tend to become an extremely important part of your life.”

“If we can understand how these early cells are regulated in the actual embryo, this knowledge will help us in the future to treat patients with diabetes, or Parkinson, or different types of blindness and other diseases,” he says. “That’s another exciting area of research.”

To edit the human embryos, the Swedish scientists will inject the embryo’s four cells with CRISPR-Cas9, a gene-editing tool comprised of only two molecules which can zero in on a particular strand of DNA, cut it out like a pair of scissors, then stitch everything back together. It’s the easiest and most precise gene editing tool at our disposal, but its power is yet to be determined. That’s why studies such as Lanner’s are important and have their place, as long as they’re done responsibly.

The video below gives you a nice rundown of what CRISPR is and what you can do with it.

Previously, in 2015, Chinese researchers caused a lot of stir after they edited human embryos to remove a gene involved in the blood disorder beta-thalassemia. Then, in 2016, another group from China did something similar only this time the DNA was modified such that the embryo would be resistant to infection with HIV. However, the two attempts involved embryos fertilized by two sperm during in vitro fertilization (IVF), making them unviable past a certain post in their development.

The embryos used by the Swedish researchers are all healthy and currently frozen after they were donated by couples who had gone through in vitro fertilization at the Karolinska University Hospital to try to have children. These embryos could theoretically fully develop into babies if they’re allowed to. Instead, Lanner says they don’t plan to let cell division work for more than 14 days. During this time, they hope to learn which genes are linked or directly involved with miscarriages. Previously, they identified which genes were expressed in 88 human embryos in the early stages of development.

In December 2015, scientists convened for an international summit in Washington, D.C., where they concluded is way far too early to allow genetically modified babies to be carried to term. However, basic research on embryos such as the one Lanner is working on was deemed acceptable. It’s still not clear where the line is drawn, though. That might happen later this year when a report authored by the gene-editing initiative will be released.

Chinese scientists prepare for first human CRISPR gene-editing trial

Image credit Pixabay

Image credit Pixabay

The CRISPR gene-editing technique has opened up a lot of doors in the scientific world – it has been used to cut out HIV genes from live animals and genetically modify human embryos. Although its benefits are indisputable, experiments such as the latter have caused controversy, as some believe that they bring us closer to changing what it means to be human.

Now, Chinese researchers from the Sichuan University’s West China Hospital have announced their plans to run a clinical trial where CRISPR will be used to modify human beings for the first time ever. In particular, the team plans to work on patients with lung cancer and turn off genes that encode a specific protein linked to a lower immune response.

Although China has come under scrutiny for their promotion of using gene-editing techniques on human beings, the new effort isn’t as controversial as the aforementioned study on human embryos. In fact, a federal panel gave the green light for a similar U.S. study back in June.

“Our goal is to develop a new type of immunotherapy using gene-editing technology that will enable the engineered immune cells to be more potent, survive longer, and thereby kill cancer cells more effectively,” the U.S. team said of their research.

The Chinese clinical trial is set to start next month and will gather T cells, which play a central role in human immunity, from patients with incurable lung cancer and conduct genetic modifications in these cells. These modifications will disable a gene that encodes the PD-1 protein, which has been shown to inhibit the immune response that protects healthy cells from attack.

After the T cells have been successfully modified and examined for editing errors, they will be allowed to multiply and then injected back into the patient’s bloodstream. Ideally, the edited cells will bolster the immune response of the lung cancer patient and aid it in attacking and killing tumor cells.

Thirty candidates are set to participate in the trial, although just one will be injected with a three dose regimen of edited cells, after which the team will monitor the patient for any positive and negative responses to the treatment before proceeding with further trials.