Tag: crispr

Baby Given World-First CRISPR Gene-Editing Treatment

In a global first, doctors in Philadelphia have used personalized CRISPR gene-editing to treat a baby with a life-threatening genetic disorder—marking a major milestone in the future of individualized medicine.

The patient is KJ Muldoon, a 9-month-old boy diagnosed shortly after birth with CPS1 deficiency, a rare and often fatal genetic condition that disrupts the body’s ability to eliminate toxic metabolic waste. “You Google ‘CPS1 deficiency,’ and it’s either fatality rate or liver transplant,” said his mother, Nicole Muldoon, in a video released by the Children’s Hospital of Philadelphia (CHOP), where KJ received his treatment.

Instead of undergoing a liver transplant, KJ became the first person in the world to be treated with a version of CRISPR designed specifically for him. The therapy, developed by CHOP and Penn Medicine, used gene-editing technology to directly target and repair his unique genetic mutation—something that had never been done before.

“Our child is sick,” said his father, Kyle Muldoon. “We either have to get a liver transplant or give him this medicine that’s never been given to anybody before, right?”

The treatment consisted of three infusions delivered to KJ’s liver, where the CRISPR system—essentially a set of molecular scissors—sought out and edited the faulty gene. “The drug is really designed only for KJ,” said Dr. Rebecca Ahrens-Nicklas, director of CHOP’s Gene Therapy for Inherited Metabolic Disorders program. “The genetic variants that he has are specific to him. It’s personalized medicine.”

According to the study published in the New England Journal of Medicine, KJ has responded well to the therapy. He’s now able to eat a higher-protein diet—something that was previously dangerous due to his condition—and he requires fewer medications. He’ll still need long-term monitoring, but doctors say early results are promising.

“While KJ will need to be monitored carefully for the rest of his life, our initial findings are quite encouraging,” Ahrens-Nicklas said in a statement. “We hope he is the first of many to benefit from a methodology that can be scaled to fit an individual patient’s needs.”

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Scientists Are Developing CRISPR Gene-editing Tools to Cure Inherited Diseases — But There’s a Catch

CRISPR-based gene-editing tools are being developed to correct specific defective sections of the genome to cure inherited genetic diseases, with some applications already in clinical trials.

However, there is a catch: under certain conditions, the repair can lead to large-scale deletions and rearrangements of DNA — as in the case of targeting the NCF1 gene in chronic granulomatous disease (CGD). This was reported by a team of researchers and physicians from the ImmuGene clinical research program at the University of Zurich.

Their findings have important implications not just for gene editing-based therapy, but also for CRISPR-mediated gene editing of animals and plants, where the same types of large-scale genetic damage could be triggered.

Indeed, because such editing is carried out with much less caution in non-human organisms, the likelihood of such large-scale damage occurring is hugely increased (see below on multiplexing).

The study also shows that attempts to avoid these problems by using adaptations of CRISPR gene editing technologies, such as prime and base editing, may not succeed.

This research on CGD is also only the latest in a series of studies that have repeatedly shown that different types of unintended mutations resulting from gene editing can affect the functioning of multiple gene systems, with potentially damaging consequences.

What is CGD?

CGD is a rare hereditary disease that affects about one in 120,000 people. The disease impairs the component of the immune system responsible for fighting off infections, which can be life-threatening to the patient.

One variant of CGD is caused by the absence of two letters in the DNA base unit gene sequence which codes for the NCF1 protein. This error results in the inability of blood cells known as neutrophils to produce an enzyme complex that plays an essential role in the immune defense against bacterial, yeast, and fungal infections.

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Can Gene-Editing Pesticides Pose Risk to Humans?

The biotech industry has been tinkering with the genetic material of living organisms and crops using CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) gene-editing technology, resulting in changes to taste profiles, extended shelf life and enhanced resistance to specific pathogens, but with unknown health consequences.1

These genetic modifications have, so far, been conducted within the confines of controlled laboratory environments. However, a disturbing new development is on the horizon — new pesticides designed to edit genes may soon be available, touted to be “more environmentally friendly” than chemical pesticides.2

A team of scientists recently raised concerns about the possible consequences of unleashing this product in an open environment, where it can affect not just its intended targets but also a wide range of nontarget organisms, possibly causing far-reaching ecological destruction. And leading the list of potential collateral damage are us humans.3

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‘Gene Scissors’ Technology Causes Unintended Changes in Chromosomes

A recently published study in Nature Genetics shows that the use of CRISPR/Cas “gene scissors” causes unintended genetic changes that are different from random mutations.

According to the study, major structural changes in chromosomes occur much more frequently in the genomic regions targeted by the “gene scissors” than would otherwise be the case.

These results also have implications for the risk assessment of plants obtained from new genetic engineering, TestBiotech reported.

According to the European Union Commission and the European Food Safety Authority, unintentional genetic changes resulting from the use of CRISPR/Cas “gene scissors” are no different from random mutations.

However, a new method of data evaluation shows that this assumption is wrong.

The use of CRISPR/Cas completely interrupts the double DNA strand, thus causing some of the chromosomes to be temporarily separated from the main section.

In the separated (distal) section, the chromosomes can restructure and larger sequences of DNA can be lost (deletions), reversed (inversions) or inserted in the wrong place (insertions).

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Pesticides Designed to ‘Edit’ the Genes of Plants, Animals, Insects — and Humans?

We’re used to gene editing being something that’s done in controlled and contained conditions in the lab, with just the final product being unleashed in the environment.

But coming down the pipeline are pesticides designed to “edit” the genes of organisms out of doors, in the uncontrolled conditions of the open environment.

Applied by spraying, irrigation, or soil pellets, these outdoor-use genetic pesticides are claimed to be more environmentally friendly than chemical pesticides.

The problem is that these genetic pesticides could also “edit” the genes of what scientists call non-target organisms — i.e., people, animals and insects in the environment could become collateral damage.

“Editing” these organisms’ genes means silencing or disrupting their normal functioning.

And the deregulation of gene editing that is occurring and being aggressively promoted around the globe means that these products could be used in open fields with no prior risk assessment, traceability, or monitoring.

Sounding the alarm about this “Wild West” scenario is a new study by an international team of scientists.

The study, based on computer predictive modeling, found that exposure to a CRISPR/Cas gene-editing pesticide could unintentionally alter the genes of a wide assortment of non-target organisms, with potentially serious or even fatal consequences.

And leading the list of potential victims of unintended gene editing are humans.

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FDA approves first use of CRISPR gene editing to treat sickle cell disease

The Food and Drug Administration (FDA) on Friday approved a new therapy for treating sickle cell disease, with this move also marking the first instance of CRISPR gene editing receiving approval from federal regulators.

The FDA approved two new treatments for sickle cell disease (SCD) on Friday, Casgevy and Lyfgenia.

Casgevy, also known as exa-cel, is developed through a partnership between Vertex Pharmaceuticals and CRISPR Therapeutics. The treatment involves taking a sickle cell patient’s own stem cells, editing them to create more fetal hemoglobin and transplanting them back into the individual.

When more fetal hemoglobin is produced, red blood cells don’t become “sickle” shaped, which is what causes the complications and pain associated with SCD. About 100,000 people in the U.S. have SCD, with the disease mostly affecting Black patients.

The FDA has approved the treatment for SCD patients 12 years old and up.

“Sickle cell disease is a rare, debilitating and life-threatening blood disorder with significant unmet need, and we are excited to advance the field especially for individuals whose lives have been severely disrupted by the disease by approving two cell-based gene therapies today,” Nicole Verdun, director of the FDA’s Office of Therapeutic Products, said in a statement.

A bone marrow transplant has long been the only curative treatment for SCD, with an ideal donor usually being a fully related sibling. There is, however, only a 1-in-4 chance that a sibling will be a match and most patients don’t have this option. Casgevy essentially makes a patient their own donor.

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Cure for HIV could be months away as first three patients are injected with new CRISPR therapy that seeks and destroys lingering pieces of virus

After four decades and over 700,000 Americans dead, gene editing experts believe they are on the cusp of curing HIV. 

Three patients in California have just been injected with genetic material along with an enzyme called CAS9 that early studies suggest can splice sections of the virus’ DNA that become lodged in human cells, eliminating it entirely.

Using the gene-editing technology CRISPR, a cure for the AIDS-causing virus could be closer on the horizon than ever thought before. 

The current trial aims to prove the treatment is safe, but data on how well it work is expected next year.

HIV was a near-certain death sentence until the mid-90s, when antiviral medications turned it into a chronic disease that people can live with. 

In total 1.2 million Americans have HIV and, even with access to medicine, have a risk of seeing their dormant infection resurface and potentially progress to AIDS.

Treatment options have evolved considerably since HIV was first identified in the early 80s. The course of treatment went from patients having to take several pills a day that might not even work well to start, to taking just a single daily pill that combines all of the best known therapies into one. 

These are known as antiretroviral therapies, or daily medications that tamp down the amount of virus in the blood to undetectable levels. These medications are effective, they are not a cure. 

A cure for HIV has eluded scientists for decades because of the unique way in which the virus hijacks the body’s own cells.   

HIV hides in immune cells in the body, where they can shield themselves from being destroyed by other immune cells. This makes hunting and killing HIV in the body difficult, because there is a risk of damaging healthy cells as well. 

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Scientists Use CRISPR To Put Genes From Alligator Into Catfish

Millions of fish are farmed in the US every year, but many of them die from infections. In theory, genetically engineering fish with genes that protect them from disease could reduce waste and help limit the environmental impact of fish farming. A team of scientists have attempted to do just that—by inserting an alligator gene into the genomes of catfish.

Americans go through a lot of catfish. In 2021, catfish farms in the US produced 307 million pounds (139 million kilogram) of the fish. “On a per-pound basis, anywhere from 60 to 70% of US aquaculture is … catfish production,” says Rex Dunham, who works on the genetic improvement of catfish at Auburn University in Alabama.

But catfish farming is also a great breeding ground for infections. From the time farmed fish are newly hatched to the time they are harvested, around 40% of the animals worldwide die from various diseases, says Dunham.

Could the new genetic modification help?

The alligator gene, which Dunham’s research turned up as a potential answer, codes for a protein called cathelicidin. The protein is antimicrobial, says Dunham—it’s thought to help protect alligators from developing infections in the wounds they sustain during their aggressive fights with each other. Dunham wondered whether animals that have the gene artificially inserted into their genomes might be more resistant to diseases.

Dunham and his colleagues also wanted to go a step further and ensure that the resulting transgenic fish couldn’t reproduce. That’s because genetically modified animals have the potential to wreak havoc in the wild should they escape from farms, outcompeting their wild counterparts for food and habitat.

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World-first CRISPR-edited sugarcane helps reduce environmental impact

Sugarcane is an important food crop, but it’s large environmental impact means there’s plenty of room for improvement. Unfortunately it’s tricky and time-consuming to breed new varieties, but now researchers have used CRISPR gene-editing to do so quickly and more easily.

Sugarcane is a key source of sugar, obviously, but that’s not its only product – the oil in the leaves and stems is often used to make bioethanol for greener fuels and plastics. But these don’t come cheap – sugarcane takes up a large percentage of farmland in many countries, which fuels deforestation. It also takes a huge amount of water to grow, and creates plenty of waste and pollution during processing.

Some of these problems can be addressed with new varieties of the plant, but sugarcane is frustratingly difficult to crossbreed due to its complex genome. It requires a lot of back-and-forth to filter out desirable traits from unwanted ones, so new versions can take years to develop.

That’s where CRISPR comes in. This powerful gene-editing tool allows scientists to switch off genes or cut them out and replace them with more useful ones. It could be useful in treating a range of diseases, but also for improving crops – and now researchers have used CRISPR to develop a couple of new varieties of sugarcane.

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For The First Time, CRISPR Gene-Editing Has Been Used on Squid

For the first time, the innovative CRISPR gene editing method has been used on squid, marking a milestone in the scientific study of these creatures – and opening up many new areas of potential research.

CRISPR enables very precise, speedy, and low-cost DNA edits. Put simple, the ingenious molecular workings of the method are often described as something that allows us to ‘cut’ and ‘paste’ genes; in humans it promises to give us a way of tackling disease and killing superbugs at the genetic level.

In this case CRISPR-Cas9 genome editing was used on Doryteuthis pealeii (the longfin inshore squid) to disable a pigmentation gene, turning off the pigmentation usually found in the squid eye and inside specialised skin cells called chromatophores.

“This is a critical first step toward the ability to knock out – and knock in – genes in cephalopods to address a host of biological questions,” says marine biologist Joshua Rosenthal, from the Marine Biological Laboratory (MBL) at the University of Chicago.

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