CRISPR & Genetic Engineering News and Discussions

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FDA clears first CRISPR treatment for a second disease, beta thalassemia

Source: CNN Health

Published 7:02 PM EST, Tue January 16, 2024

CNN — The US Food and Drug Administration has approved a second use for the first CRISPR-based medicine, Casgevy, which was approved in December to treat sickle cell disease.

The groundbreaking treatment can now also be used to treat transfusion-dependent beta thalassemia in people 12 and older. Like sickle cell, beta thalassemia is an inherited blood disorder. The FDA’s decision was expected, but it comes about two months earlier than the agency’s deadline for acting, called the PDUFA date.

To make Casgevy, a person’s stem cells are genetically modified using a precision gene editing technique called CRISPR/Cas9. The modified cells are then transplanted back into the body, where they grow and multiply and increase the production of hemoglobin, which decreases symptoms. The treatment lists for $2.2 million for both sickle cell disease and beta thalassemia.

“Today’s approval is an important step in the advancement of an additional treatment option for individuals with beta-thalassemia, a debilitating disease that places individuals at risk of many serious health problems,” said Dr. Nicole Verdun, director of the Office of Therapeutic Products within the FDA’s Center for Biologics Evaluation and Research, in a news release.

Read more: https://www.cnn.com/2024/01/16/health/c ... index.html

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CRISPR off-switches: A path towards safer genome engineering?
https://phys.org/news/2024-01-crispr-pa ... enome.html
by University of Michigan

Using CRISPR, an immune system bacteria use to protect themselves from viruses, scientists have harnessed the power to edit genetic information within cells. In fact, the first CRISPR-based therapeutic was recently approved by the FDA to treat sickle cell disease in December 2023. That therapy is based on a highly studied system known as the CRISPR-Cas9 genetic scissor.

However, a newer and unique platform with the potential to make large-sized DNA removals, called Type I CRISPR or CRISPR-Cas3, waits in the wings for potential therapeutic use.

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Gene therapy restores hearing in children with hereditary deafness

https://medicalxpress.com/news/2024-01- ... fness.html

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Groundbreaking gene therapy trial allows 5 children born deaf to hear
By Michael Irving
January 28, 2024

A breakthrough clinical trial using gene therapy has restored hearing to five children born deaf. After six months, the children were able to recognize speech and hold conversations, raising hopes for wider use in the near future.

The patients in the trial suffered from a genetic condition called autosomal recessive deafness 9 (DFNB9), which is caused by a mutation in a gene called OTOF. This gene produces the otoferlin protein, which helps transmit electrical pulses from the cochlea to the brain, where it can be interpreted as sound – but without it, those signals never get there. Because it’s caused by a single mutation, and doesn’t involve any physical damage to cells, the team says DFNB9 was the perfect candidate for this kind of gene therapy.

The gene therapy involves packaging the OTOF gene into viral carriers, and injecting the mix into the inner ear fluid. The viruses then sought out cells in the cochlea and inserted the gene into them, which allows them to start manufacturing the missing otoferlin protein and restore hearing.

https://newatlas.com/medical/born-deaf- ... e-therapy/

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Using CRISPR technology, researchers succeed in growing tomatoes that consume less water without compromising yield
https://phys.org/news/2024-01-crispr-te ... nsume.html
by Tel-Aviv University

A new discovery by Tel Aviv University has succeeded in cultivating and characterizing tomato varieties with higher water use efficiency without compromising yield. The researchers, employing CRISPR genetic editing technology, were able to grow tomatoes that consume less water while preserving yield, quality, and taste.

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Researchers identify potential way to treat genetic epilepsy by replacing 'lost' enzyme
https://medicalxpress.com/news/2024-02- ... nzyme.html
by The Francis Crick Institute

Scientists at the Francis Crick Institute have found a new treatment target for CDKL5 deficiency disorder (CDD), one of the most common types of genetic epilepsy.

CDD causes seizures and impaired development in children, and medications are limited to managing symptoms rather than tackling the root cause of the disease. The disorder involves losing the function of a gene producing the CDKL5 enzyme, which phosphorylates proteins, meaning it adds an extra phosphate molecule to alter their function.

Following recent research from the same lab showing that a calcium channel could be a target for therapy for CDD, the team has now identified a new way to potentially treat CDD by boosting another enzyme's activity to compensate for the loss of CDKL5.

In research published in Molecular Psychiatry, the scientists studied mice that don't make the CDKL5 enzyme. These mice show similar symptoms to people with CDD, such as impaired learning or social interaction.

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Checkout the CRISPR Journal for several articles related to this thread: https://home.liebertpub.com/publication ... ournal/642

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Single-dose gene therapy may stop deadly brain disorders in their tracks
By Paul McClure
February 15, 2024

Researchers have developed a single-dose genetic therapy that can clear protein blockages that cause motor neurone disease, also called amyotrophic lateral sclerosis, and frontotemporal dementia, two incurable neurodegenerative diseases that eventually lead to death.

In healthy neurons, TAR DNA-binding protein 43 (TDP-43) is naturally produced and important for their healthy function. However, TDP-43 can be modified after synthesis, leading to its accumulation and aggregation in the wrong part of the cells, preventing them from working properly. These build-ups are associated with devastating neurodegenerative diseases like motor neurone disease (MND), also known as amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease, and frontotemporal dementia (FTD).

https://newatlas.com/medical/incurable- ... e-therapy/

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Study explores a novel and precise mitochondrial gene editing method
https://phys.org/news/2024-02-explores- ... ethod.html
by Korea University College of Medicine

Gene editing technology could revolutionize the treatment of genetic diseases, including those that affect the mitochondria—cell structures that generate the energy required for the proper functioning of living cells in all individuals. Abnormalities in the mitochondrial DNA (mtDNA) could lead to mitochondrial genetic diseases.

Targeted base editing of mammalian mtDNA is a powerful technology for modeling mitochondrial genetic diseases and developing potential therapies. Programmable deaminases, which consist of a custom DNA-binding protein and a nucleobase deaminase, enable precise mtDNA editing.

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‘Bad’ cholesterol gene silenced without altering the DNA sequence
By Paul McClure
February 28, 2024
https://newatlas.com/science/epigenetic ... -silenced/

By silencing the gene responsible for regulating ‘bad’ cholesterol without altering the primary DNA sequence, researchers have shown that it’s possible to use epigenetic editing to treat diseases rather than conventional DNA-breaking gene editing technology, which risks unintended effects.

Because identical twins develop from a single fertilized egg, they have the same genome, the entire set of genetic material found in an organism. So, any differences between them, even in traits with a significant genetic component – say one develops heart disease and the other doesn’t – are due to their environments. This is known as epigenetics.

Genes in DNA are ‘expressed’ when they’re read and transcribed into RNA, which is then translated into proteins. It’s proteins that determine many of a cell’s characteristics and functions. Epigenetic changes can boost or silence the transcription of specific genes, ramping up or inhibiting associated protein production, but they don’t change the genome. These changes, which are reversible, can affect a person for their entire life and mediate a lifelong dialogue between genes and the environment.

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Team performs the first gene therapy tests in a whole human liver
https://medicalxpress.com/news/2024-03- ... liver.html
by Children's Medical Research Institute

In a worldwide first-of-its-kind study published in the journal Nature Communications this week, a team of scientists from Children's Medical Research Institute (CMRI) have tested novel gene therapies in a whole human liver, with the goal of developing more effective treatments for life-threatening inherited diseases.

Gene therapy is a revolutionary approach to treating serious genetic diseases that most commonly involves replacing or repairing a faulty gene. The most efficient delivery systems today are those based on a harmless virus named adeno-associated virus (AAV) that has a natural ability to carry genetic information into human cells.

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CRISPR Gene Editing Eliminates HIV From Infected Cells
The team hopes to turn this into a cure for HIV.
By Ryan Whitwam March 21, 2024

The stigma surrounding HIV stymied early efforts to understand and treat the infection, but medical science has reached the point where we can start talking about a cure. A team of Dutch scientists has previewed research to be revealed at this year's European Congress of Clinical Microbiology and Infectious Diseases next month. For the first time, the CRISPR-Cas9 gene editing system has been successfully employed to cut HIV out of infected cells. The researchers hope this could one day lead to treatment that renders patients free of the virus.

CRISPR has received a great deal of attention in recent years, including winning its discoverers a Nobel Prize in 2020. Originating in bacterial cells, CRISPR is a defense mechanism that slices up the genes of invading viruses. Scientists repurposed it using guide DNA to point the cuts at specific genomic sequences. In this way, we can remove and even replace those sequences inside living cells. And this research is finally bearing fruit; CRISPR is the basis of one of two new gene editing treatments that promise to cure Sickle Cell Disease. But can it do the same for HIV?

https://www.extremetech.com/science/cri ... cted-cells

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Scientists create novel technique to form human artificial chromosomes

by Perelman School of Medicine at the University of Pennsylvania
https://phys.org/news/2024-03-scientist ... somes.html

Human artificial chromosomes (HACs) capable of working within human cells could power advanced gene therapies, including those addressing some cancers, along with many laboratory applications, though serious technical obstacles have hindered their development. Now a team led by researchers at the Perelman School of Medicine at the University of Pennsylvania has made a significant breakthrough in this field that effectively bypasses a common stumbling block.

In a study published in Science, the researchers explained how they devised an efficient technique for making HACs from single, long constructs of designer DNA. Prior methods for making HACs have been limited by the fact that the DNA constructs used to make them tend to join together—"multimerize"—in unpredictably long series and with unpredictable rearrangements.

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DNA nanotube rings: Research team develops important building block for artificial cells
https://phys.org/news/2024-03-dna-nanot ... block.html
by Adriane Koller, TU Dortmund University

During cell division, a ring forms around the cell equator, which contracts to divide the cell into two daughter cells. Together with researchers from Heidelberg, Dresden, Tübingen and Harvard, Professor Jan Kierfeld and Lukas Weise from the Department of Physics at TU Dortmund University have succeeded for the first time in synthesizing such a contractile ring with the help of DNA nanotechnology and uncovering its contraction mechanism. The results have been published in Nature Communications.

In synthetic biology, researchers try to recreate crucial mechanisms of life in vitro, such as cell division. The aim is to be able to synthesize minimal cells. The research team led by Professor Kerstin Göpfrich from Heidelberg University has now synthetically reproduced contractile rings for cell division using polymer rings composed of DNA nanotubes.

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Scientist who gene-edited babies is back in lab and ‘proud’ of past work despite jailing

Mon 1 Apr 2024 05.52 BST

A Chinese scientist who was imprisoned for his role in creating the world’s first genetically edited babies says he has returned to his laboratory to work on the treatment of Alzheimer’s and other genetic diseases.

In an interview with a Japanese newspaper, He Jiankui said he had resumed research on human embryo genome editing, despite the controversy over the ethics of artificially rewriting genes, which some critics predicted would lead to demand for “designer babies”.

“We will use discarded human embryos and comply with both domestic and international rules,” He told the Mainichi Shimbun, adding that he had no plans to produce more genome-edited babies. Previously, He had used a tool known as Crispr-Cas9 to rewrite DNA in embryos.

In 2019 a court in China sentenced He to three years in prison for violating medical regulations after he claimed the previous year that he had created genetically modified twin sisters, Lulu and Nana, before birth.

His experiments sent shockwaves through the medical and scientific world. He was widely condemned for having gone ahead with the risky, ethically contentious and medically unjustified procedure with inadequate consent from the families involved.

https://www.theguardian.com/science/202 ... ack-in-lab

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Gene editing technique shows promise for effectively curing a hereditary liver disease
https://medicalxpress.com/news/2024-04- ... liver.html
by University of Helsinki

Argininosuccinate lyase deficiency (ASLD), also known as argininosuccinic aciduria, is a severe metabolic disease where the body does not process proteins normally, instead resulting in a very dangerous accumulation of argininosuccinic acid and ammonia. Excess ammonia causes disturbances of consciousness, coma and even death.

In Finland, infants are screened for ASLD to determine the disease risk before symptoms develop. The treatment is an extremely strict lifelong diet, and in severe cases, a liver transplant.

Researchers from the University of Helsinki and HUS Helsinki University Hospital have now succeeded in correcting the gene defect associated with argininosuccinic aciduria and have demonstrated that the harmful metabolism caused by the disease can be cured.

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Scientists discover potential treatment approaches for polycystic kidney disease
https://medicalxpress.com/news/2024-04- ... ystic.html
by National Institutes of Health

Researchers have shown that dangerous cysts, which form over time in polycystic kidney disease (PKD), can be prevented by a single normal copy of a defective gene. This means the potential exists that scientists could one day tailor a gene therapy to treat the disease. They also discovered that a type of drug, known as a glycoside, can sidestep the effects of the defective gene in PKD. The discoveries could set the stage for new therapeutic approaches to treating PKD, which affects millions worldwide.

The study is published in Cell Stem Cell.

Scientists used gene editing and 3D human cell models known as organoids to study the genetics of PKD, which is a life-threatening, inherited kidney disorder in which a gene defect causes microscopic tubes in the kidneys to expand like water balloons, forming cysts over decades. The cysts can crowd out healthy tissue, leading to kidney function problems and kidney failure. Most people with PKD are born with one healthy gene copy and one defective gene copy in their cells.

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Research team builds first tandem repeat expansions genetic reference maps
https://medicalxpress.com/news/2024-04- ... netic.html
by Pat Harriman, University of California, Irvine

A research team led by the University of California, Irvine has built the first genetic reference maps for short lengths of DNA repeated multiple times which are known to cause more than 50 lethal human diseases, including amyotrophic lateral sclerosis, Huntington's disease and multiple cancers.

The UC Irvine Tandem Genome Aggregation Database enables researchers to study how these mutations—called tandem repeat expansions—are connected to diseases, to better understand health disparities and to improve clinical diagnostics.

The study, published online today in the journal Cell, introduces the UC Irvine TR-gnomAD, which addresses a critical gap in current biobank genome sequencing efforts. Although TR expansions constitute about 6 percent of our genome and substantially contribute to complex congenial conditions, scientific understanding of them remains limited.

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Gene editing crops to be colourful could aid weeding, say scientists

Wed 17 Apr 2024 16.00 BST

Genetically engineering crops to be colourful could help farmers produce food without pesticides, as it would make it easier to spot weeds, scientists have said.

This will be increasingly important as hardy, climate-resistant “weeds” are grown for food in the future, the authors have written in their report published in the journal Trends in Plant Science.

The lead author Michael Palmgren, a plant scientist from the University of Copenhagen, told the Guardian: “It can be modifications of hairs, leaf shape, light emitted at wavelength we cannot see. Anything could work on a large scale. The challenge of distinguishing a weed from a crop becomes imminent when we start breeding weeds.”

He said new crops were hard to distinguish from weeds, so it would be important to find a way to tell them apart. The paper suggests the crops’ genomes could be altered so they express pigments such as anthocyanins, which give blueberries their colour, or carotenoids, which make carrots orange.

“One example that we give in our opinion paper, fat hen (Chenopodium album), is grown for its nutritious seeds in India and Nepal and was a food source in Europe in the iron age – seeds are commonly found in the stomach of bog bodies,” said Palmgren.

https://www.theguardian.com/science/202 ... scientists

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New gene therapy for metachromatic leukodystrophy proves effective in mice
https://medicalxpress.com/news/2024-04- ... ctive.html
by Marie Simon, Paris Brain Institute

Metachromatic leukodystrophy is a rare genetic disorder that mainly affects young children and results in severe neurological symptoms accompanied by a loss of motor and intellectual capacities. At Paris Brain Institute, Françoise Piguet and her colleagues have developed a gene therapy treatment capable of correcting the primary anomaly observed in the disease: the accumulation of sulfatides in the brain and spinal cord. Effective in mice, as shown by results published in Molecular Therapy—Methods & Clinical Development, this technique paves the way for clinical trials.

Metachromatic leukodystrophy affects between one and nine people out of 100,000 and manifests itself mainly in childhood and adolescence—with 10 to 20% of cases observed in adulthood. The disease is hereditary but requires both parents to carry the mutated ARSA gene, which controls the production of the enzyme arylsulfatase A.

The depletion of this enzyme in the body leads to an abnormal accumulation of specific lipids (sulfatides) in the white matter of the central nervous system, peripheral nerves, kidneys and gallbladder.