Katarzyna Glowacka, a postdoctoral researcher at the Carl R. Woese Institute for Genomic Biology (IGB) at the University of Illinois at Urbana-Champaign, led the project. Together, she and the research team modified the expression of a single gene to increase the levels of a photosynthetic protein known as PsbS in tobacco plants.
Increasing PsbS essentially tricks the plant into partially closing its stomata — tiny pores on the leaves that allow carbon dioxide to enter for photosynthesis, but simultaneously let water escape. With the stomata only partially open, the tobacco plant doesn’t lose as much water.
The amount of carbon dioxide the plant has, surrounding humidity, as well as the quality and quantity of light can impact whether the stomata are open or closed. The PsbS proteins signal to the plant how much light is nearby, so an artificially increased level of PsbS indicating that there isn’t enough light for photosynthesis, prompting the stomata to close.
Ultimately, tweaking the amount of PsbS increased the tobacco plant’s water-efficiency, or the ratio of how much carbon dioxide enters the plant to how much water is lost, by 25 percent without sacrificing the plant’s yield.
“These plants had more water than they needed, but that won’t always be the case,” Glowacka explained in a press release. “When water is limited, these modified plants will grow faster and yield more — they will pay less of a penalty than their non-modified counterparts.”
PsbS is found in all plants, meaning the experiment done with tobacco could work for other plants too. To prove this, the team will now attempt to improve the water-efficiency of food crops, and test the crops’ efficiency when water is limited.
Another postdoctoral researcher at the IGB, Johannes Kromdijk, said in the same press release: “Making crop plants more water-use efficient is arguably the greatest challenge for current and future plant scientists.” Undoubtedly, despite the continuous public debate surrounding whether genetically modified organisms (GMOs) are safe sources of food, these modifications will continue to improve crop quality and resiliency.
A person’s lifetime risk of developing heart disease depends on many factors. Several are related to lifestyle, so if a person is at a high-risk of developing heart disease, their doctor might recommend they get more exercise, improve their eating habits, or quit smoking. Other risk factors aren’t so easily altered – namely, a person’s genes – but as a new study has shown, that might change in the age of gene editing.
Some people have a naturally occurring mutation in a gene called ANGPTL3, which plays a role in the regulation of fats in our blood called triglycerides. Having too many triglycerides increases our risk of developing heart disease, so doctors usually recommend patients change their diets or take medications to lower these levels.
However, the ANGPTL3 mutation seems to lower the person’s risk of developing cardiovascular disease without causing any harmful side effects. Now, researchers from the University of Pennsylvania have tested a gene-editing technique inspired by these people who lucked out in the genetic lottery.
A First Step
For their study, which was published in the journal Circulation, the team used a CRISPR-like technique called base editing. First, they injected healthy mice with the base-editing treatment to modify the ANGPTL3 gene. Then, they compared the animals’ blood fat levels with those of untreated mice. The levels of the treated mice were up to 30 percent lower than those of the mice that hadn’t been treated.
Next, the researchers set out to determine if their treatment could help patients with a rare inherited disorder called homozygous familial hypercholesterolemia. These patients have very few effective options for treatments and carry a severe risk of heart disease as a result. If doctors could forcibly lower their triglyceride levels by “turning off” a gene, it could be life-saving.
To test this possibility, the team created a mouse model of homozygous familial hypercholesterolemia. After two weeks, the mice given the base-editing treatment showed substantially reduced triglycerides – up to 56 percent – over the mice that weren’t treated. The modified gene appeared to help treat the rare condition.
For the time being, researchers have only tested the treatment in mice, but these initial results are encouraging. If researchers can find a way to make it work in humans, the technique could potentially help patients whose triglyceride levels aren’t responding to lifestyle changes and medication, as well as those with homozygous familial hypercholesterolemia.
The team is now preparing for the next step toward human trials, which will involve injecting human liver cells into mice in order to test the treatment’s effectiveness and safety on human ANGPTL3 genes. If all goes well, the team could move ahead with clinical trials. According to a press release statement by the study’s lead author, Kiran Musunuru, patients with homozygous familial hypercholesterolemia could be just five years away from “a one-time CRISPR ‘vaccination’.”
Over the past few years, CRISPR has been making headlines. Experts predict that this gene editing technology will transform our planet, revolutionizing the societies we live in and the organisms we live alongside. Compared to other tools used for genetic engineering, CRISPR (also known by its more technical name, CRISPR-Cas9) is precise, cheap, easy to use, and remarkably powerful.
Discovered in the early 1990s, and first used in biochemical experiments seven years later, CRISPR has rapidly become the most popular gene editing tool among researchers in fields such as human biology, agriculture, and microbiology.
Scientists are still in the earliest stages of figuring out how we can use CRISPR to change the world for the better. Of course, the power to alter DNA — the source code of life itself — brings with it many ethical questions and concerns. With this in mind, here are some of the most exciting uses for this revolutionary technique, and the hurdles that might slow or prevent these technologies from reaching their full potential.
1. CRISPR Could Correct The Genetic Errors That Cause Disease
Hypertrophic cardiomyopathy (HCM) is a heart condition that affects roughly 1 in every 500 people worldwide. Its symptoms are painful and often deadly. Mutations in a number of dominant genes cause the heart tissues to stiffen, which can lead to chest pain, weakness, and, in severe cases, sudden cardiac arrest. Thanks to recent medical advances, the average life expectancy of someone with HCM is close to that of the general population, but the condition can lead to life-threatening situations if left untreated.
But someday, we may be able to use gene editing to cure this disease once and for all.
In summer 2017, scientists at the Oregon Health and Science University used CRISPR to delete one of these defective genes ina number of viablehuman embryos. The results were promising: Of the 54 embryos that were injected with the CRISPR-Cas9 machinery 18 hours after fertilization, 36 did not show any mutations in the gene (practically no chance of developing the disease) and 13 were partially free of mutations (with a 50 percent chance of inheriting HCM).
Off-target genetic mutations and mosaics (only some cells adopt the changes, meaning that a fraction of people would inherit the mutation) were only present in 13 of the 54 embryos.
To further reduce the chance that only some cells would be changed, the researchers carried out another experiment in which they corrected the same gene in embryos directly at the time of fertilization. They found that only one was a mosaic — an impressive result, making the study substantially more efficient than similar studies (a 2015 clinical trial in China was not able to eliminate the possibility of mosaics).
“By using this technique, it’s possible to reduce the burden of this heritable disease on the family and eventually the human population,” Shoukhrat Mitalipov, lead author of the study and a researcher at the Oregon Health and Science University, said in a press release. Catching the mutation at in the earliest stages of embryonic development would either reduce or eliminate the need for treatment later in a patient’s life.
While some stem-cell scientists questioned if these dozens of mutations were actually fixed, the research helped scientists better understand CRISPR’s efficacy. Moreover, one of the co-authors of the HCM study has already expressed interest in applying the same technique to specific gene mutations (BRCA1 and 2) that increase the risk of breast cancer.
That said, scientists know that changing the genetic code in human embryos could have unintended consequences. What if CRISPR makes changes in the wrong place and unintentionally alters or removes healthy genes? How could that affect the patient?
In some parts of the world, such as China, scientists are free to experiment on human embryos largely unfettered. But this is not the case in the United States, Canada, or the United Kingdom.
In the U.S., the Food and Drug Administration (FDA) currently does not consider using public funding for studies that alter genes that can be inherited (the embryos in the Oregon researchers’ study were not destined for implantation and the study was funded privately). In Canada, editing genes that can be passed down to future generations is a criminal offense with a maximum penalty of ten years in jail. Meanwhile, in the U.K., the Human Fertilization and Embryology Authority gave a team of scientists in London the license to edit genes in human embryos in 2016. Scientists in the U.K. are hoping this will establish a precedent, and keep the door open for future applications.
2. CRISPR Can Eliminate the Microbes That Cause Disease
Though treatments for HIV have turned the infection from a virulent killer to a livable health condition, scientists still haven’t found a cure. That could change with CRISPR. In 2017, a team of Chinese researchers successfully increased resistance to HIV in mice by replicating a mutation of a gene that effectively prevents the virus from entering cells. For now, scientists are only conducting these experiments in animals, but there’s reason to think the same methods could work in humans. The mutation that encourages HIV resistance naturally occurs in a small percentage of people. By using CRISPR to introduce the mutation to human stem cells that lack it, researchers could substantially bolster HIV resistance in humans in the future.
Another gene-editing trial in China is due to begin in July 2018 and will attempt to use CRISPR to disrupt the genes of the human papillomavirus (HPV) — a virus that has been shown to cause cervical cancer tumor growth — effectively destroying it.
In a slightly different approach, scientists in North Carolina used CRISPR to engineer bacteriophages, a type of virus that infects and duplicates itself inside a bacterium, to kill harmful bacteria. Since the 1920s, phages have been used in clinical trials to treat bacterial infections. But harvesting them from nature proved difficult, a lack of understanding at the time made results unpredictable, and the growing antibiotics market made their use unpopular.
Even today, some researchers fear that flooding the body with a large volume of phages may trigger immune reactions or cause antibiotic-resistant bacteria to also become resistant to phages that would otherwise eliminate them.
In February 2017, Harvard geneticist George Church made a surprising announcement before the annual meeting of the American Association for the Advancement of Science. He claimed his team was just two years away from developing an embryo for an elephant-mammoth hybrid.
Church hopes that bringing back the woolly mammoth could keep global warming in check. “[Mammoths] keep the tundra from thawing by punching through snow and allowing cold air to come in,” Church told the New Scientist.
Church and his team are hoping to use CRISPR to combine genetic material from the Asian elephant (an endangered species that could potentially be saved) and the woolly mammoth. Samples of the latter were harvested from DNA recovered from frozen hairballs found in Siberia. By adding the mammoth’s genome to that of the Asian elephant, the resulting organism would have characteristics common to the woolly mammoth, such as long fur, which would serve as insulation in cold climates. The end goal is to implant this hybrid embryo into an elephant and bring it to full term, according to the New Scientist.
The work is promising, but many experts think that Church’s timeline is a bit too optimistic. Even if researchers had a functional hybrid embryo, growing it inside an artificial womb as Church suggests will be yet another hurdle to overcome. Granted, Church’s lab is already capable of growing a mouse embryo inside an artificial womb for half of its gestation period, about 10 days. But that doesn’t guarantee that we’ll witness the birth of a woolly mammoth hybrid in the next couple of years.
4. CRISPR Could Create New, Healthier Foods
CRISPR gene editing has proven to be promising in the field of agricultural research. Scientists from Cold Spring Harbor Laboratory in New York used the tool to increase the yield of tomato plants. The lab developed a method to edit the genes that determine tomato size, branching architecture and, ultimately, shape of the plant for a greater harvest.
“Each trait can now be controlled in the way a dimmer switch controls a light bulb,” said lead researcher and Cold Spring Harbor Laboratory professor Zachary Lippman in a press release. “We can now work with the native DNA and enhance what nature has provided, which we believe can help break yield barriers.”
High-yield crops to feed a hungry world are just the beginning — scientists hope CRISPR could also help shed the stigma surrounding genetically modified organisms (GMOs). In 2016, agriculture technology company DuPont Pioneer announced a new variety of CRISPR-edited corn that, because of how researchers altered its genes, is technically not a GMO.
The distinction between GMOs and gene-edited crops is fairly simple. Traditional GMOs are made by inserting foreign DNA sequences into a crop’s genome, transmitting traits or properties to future organisms. Gene editing is more precise than that: it makes precise alterations to genes in specific locations of the native genome, often knocking out certain genes or changing their location, all without introducing foreign DNA.
While GMOs have been contentious among consumers, companies like DuPont Pioneer are hoping that gene-edited foods will be better received. In the decades that GMOs have been available in the American market, scientists have detected no health risks, though even the biggest proponents of GMOs admit that scientists still don’t know all of the long-term risks. The same goes for crops edited by CRISPR. Of course, scientists will continue to test and evaluate these crops to ensure there are no unexpected side effects, but this early work is remarkably promising. Eventually, CRISPR-edited crops will likely flood global markets.
5. CRISPR Could Eradicate The Planet’s Most Dangerous Pest
Gene-editing techniques like CRISPR could directly combat infectious diseases, but some researchers have decided to slow the spread of disease by eliminating its means of transmission. Scientists at the University of California, Riverside developed a kind of mosquito that is uniquely susceptible to changes made with CRISPR, giving scientists unprecedented control over the traits that the organism passes to its offspring. The result: yellow, three-eyed, wingless mosquitoes, created by altering genes responsible for eye, wing, and cuticle development.
By disrupting target genes in multiple locations of the mosquito’s genes, the team is testing a “gene drive” system to spread these inhibiting properties. Gene drives are a way to essentially ensure that a genetic trait will be inherited. By impairing the mosquito’s flight and vision, the Riverside team is hoping to greatly reduce its ability to spread dangerous infectious diseases among humans, such as dengue and yellow fever.
Other researchers are getting rid of mosquito populations by interfering with how they reproduce. At the Imperial College London in 2016, a team of researchers used CRISPR to target female reproduction of the type of mosquito that carries malaria through a gene drive system that influenced female-sterility traits into being more likely to be inherited.
But interfering with mosquito populations could have unforeseen consequences. Eliminating a species, even one that doesn’t appear to have much ecological value, could upset the careful balance of ecosystems. That could have disastrous consequences, such as disrupting the food web or increasing the risk that diseases like malaria could be spread by different species entirely.
Current scientific advancements show that CRISPR is not only an extremely versatile technology, it’s proving to be precise and increasingly safe to use. But a lot of progress still has to be made; we are only beginning to see the full potential of genome-editing tools like CRISPR-Cas9.
Technological and ethical hurdles still stand between us and a future in which we feed the planet with engineered food, eliminate genetic disorders, or bring extinct animal species back to life. But we are well on our way.
At first glance, CRISPR gene editing looks like the solution to all the world's ills: it could treat or even cure diseases, improve birth rates and otherwise fix genetic conditions that previously seemed permanent. You might want to keep your expecta… Engadget RSS Feed
As animals get older, the electrophysiology of their hippocampal connections begins to degrade. A new study appears to have identified the family of genes that are responsible, demonstrating how a single gene can have a broad effect on age-related decline.
The key component seems to be a protein called FKBP, which is responsible for calcium release within neurons. In the study, rats were injected with viruses engineered to promote overexpression of FKBP1b, and then observed as they attempted to find an underwater platform in a water maze. They were later euthanized so that the researchers could analyze gene expression in their hippocampi.
The rats who received the treatment were found to perform much better than control animals of the same age. What’s more, the hippocampal expression levels of over 800 other genes had been altered as well as the FKBP1b overexpression. The vast majority of these changes caused levels to resemble younger rats more closely than older rats.
Excessive calcium release had already been linked to age-related decline by an earlier study, where increased FKBP expression was seen to increase cognitive function in older rats. The new findings raise further questions, but there are hopes that it could lead to some new ideas in how we respond the mental changes humans experience in old age.
The next step for the researchers involved with this project is to figure out why FKBP levels decrease as animals get older, and what can be done to prevent this from happening. It’s been suggested that metabolic conditions or changes to other cells might be the culprit.
“Another key question is whether Ca2+ dysregulation is why aging is the leading risk factor for Alzheimer’s disease,” wrote the paper’s lead author J.C. Gant in email correspondence with Futurism. “In most neurodegenerative disorders age is a major risk factor and it may be that changes in neuronal calcium are a trigger for multiple diseases. This we do not know, yet.”
Of course, there’s a need for clinical trials to determine whether FKBP expression could be safely manipulated in humans. Gant is hopeful that such trials could take place sooner rather than later, given that we’re already seeing studies using adeno-associated viral vectors to increase gene expression in specific areas of the brain. A microsyringe would be used to inject the virus into the region where it’s needed (in this case the hippocampus).
“Although clinical trials must be run to determine the viability, the debilitating nature of memory loss in normal aging and extreme cases such as Alzheimer’s makes minimally-invasive measures such as this seem more and more viable with respect to alternative consequences of not treating the disease,” explained Gant.
The findings of this study don’t necessarily mean that we have a solution to the way our brains wane as we get older. However, they do offer up some intriguing possibilities when it comes to figuring out what is actually happening inside our bodies that causes this decline to take place.
Last month, the FDA approved a gene therapy called Luxturna, which can treat a rare eye disease that causes blindness. Now the treatment has a price tag, CNBC reports. It will cost $ 425,000 per eye, and while $ 850,000 is steep, it's lower than the $ 1… Engadget RSS Feed
The FDA has approved a new gene therapy that proves the technique can also be used to treat a variety of diseases other than cancer. According to the agency's announcement, the therapy called Luxturna can treat biallelic RPE65 mutation-associated ret… Engadget RSS Feed
Almost half of all deafness cases are caused by genetic factors, but treating inherited hearing loss is tricky. Now, scientists have shown they can stop a type of progressive hearing loss – caused by a genetic mutation – using the CRISPR-Cas9 gene editing tool. A team led by David Liu at Harvard University injected a CRISPR protein capable of targeting a genetic mutation responsible for a type of deafness into live mice’s ears. The mice used in the study, published in Nature, had a mutated copy of the Tmc1 gene, which causes eventual deafness, alongside one normal copy of the gene. The one-time CRISPR treatment slowed down deafness in the mice.
The mutant Tmc1 gene is dominant, so the presence of just one copy will lead to progressive hearing loss in humans and mice alike. The mutation kills off the ear’s hair cells, which detect sound, over time. Mice with one mutant Tmc1 copy have substantial hearing loss after four weeks, and are essentially deaf after eight weeks – in humans, this progression often starts in childhood and could last decades.
But when the CRISPR-Cas9 editing tool was injected into a mouse’s ear, it displayed superior hair cell health and survival than in the same mouse’s other ear, which did not receive the same injection.
The mice with the mutated gene that received treatment still responded to loud noises at eight weeks, whereas the mice that didn’t receive the treatment had no startle response. “We were really excited when we observed hearing preservation in the injected ears but not the uninjected ears of the same mouse,” reflected Liu, in comments shared with Futurism via email. “Especially since we were not sure at that point how well the promising editing results we observed in cultured cells in a dish would translate into live animals.”
The mutated copy of Tmc1 differs from its normal counterpart by only a single DNA letter. Still, Liu and his team were able to disrupt the former while leaving the latter unchanged thanks to the CRISPR Cas-9 tool, which Liu described as a “pleasant surprise.”
Furthermore, while only a small amount of the target cells were actually repaired – 10 to 25 percent – researchers observed an improvement to the health of the mice’s hair cells. The team also observed a marked improvement in the treated mice’s hearing. At four weeks, treated mice could hear sounds that were 15 decibels quieter than their untreated counterparts. While there are still challenges to overcome, these successes bode well for the treatment.
Moving forward, delivery methods, improved efficacy, and an investigation into potential side effects are top priorities. Liu hopes to perform further tests on larger animal models, as well as further research into the possibility of using the same technique to address other diseases with a genetic component.
These steps are crucial if we’re to find out whether the procedure could give medical professionals a way to restore their patients’ hearing. “There’s still quite a bit of work to do before this approach might be used in humans,” Liu said.
Scientists have successfully tweaked the DNA of mice with a specific genetic mutation to prevent them from going completely deaf. If the gene-editing technique is proven safe, it could one day be used to treat the same type of hearing loss in people.
Researchers injected the gene-editing tool CRISPR-Cas9 inside the ears of live mice with a deafness-causing genetic mutation. The molecular scissors were able to precisely cut the disease-causing copy of the gene without disrupting the healthy copy, according to a study published today in Nature. Even though the researchers think they were able to repair only a small fraction of cells in the ear, that prevented treated mice from losing all their hearing.