CRISPR & Genetic Engineering News and Discussions

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caltrek
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AI-designed Protein Awakens Silenced Genes, One by One
March 4, 2022

https://www.eurekalert.org/news-releases/945500

Introduction:
(EurekAlert) By combining CRISPR technology with a protein designed with artificial intelligence, it is possible to awaken individual dormant genes by disabling the chemical “off switches” that silence them. Researchers from the University of Washington School of Medicine in Seattle describe this finding in the journal Cell Reports.

The approach will allow researchers to understand the role individual genes play in normal cell growth and development, in aging, and in such diseases as cancer, said Shiri Levy, a postdoctoral fellow in UW Institute for Stem Cell and Regenerative Medicine (ISCRM) and the lead author of the paper.

“The beauty of this approach is we can safely upregulate specific genes to affect cell activity without permanently changing the genome and cause unintended mistakes,” Levy said.
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New Cas9 model maps DNA cutting behavior for the first time
https://phys.org/news/2022-03-cas9-dna-behavior.html
by Delft University of Technology
Researchers from the TU Delft have come up with a physical-based model that establishes a quantitative framework on how gene-editing with CRISPR-Cas9 works, and allows them to predict where, with what probability, and why targeting errors (off-targets) occur. This research, which has been published in Nature Communications, gives us a first detailed physical understanding of the mechanism behind the most important gene editing platform of today.

The discovery of the CRISPR-Cas9 protein has greatly simplified gene editing, and raised hopes to find a cure to many hereditary diseases. However, routine and safe use of this technique in human therapeutics requires extreme precision and predictability of any off-target effects. A research team lead by Martin Depken at TU Delft's department of Bionanoscience has now demonstrated a new, physical-based model that greatly improves on existing models: not only does the model predict where the DNA is likely to be cut, but also with what probability this will happen.

Physics-based approach to understand Cas9 gene-editing

A great limitation of current bioinformatics models for gene editing lies in the fact that they are binary in nature: they classify targets on the genome as either likely or unlikely to be cut. These models focus only on very high-probability targeting errors (off-targets), and will miss the many lower probability off-targets that together could amount to the majority of editing errors in the genome. Now, the new physical model which the researchers created takes into account both high-probability and low-probability off-targets; it can be used to physically characterize any Cas9 variant and predict the probability that any site will be cleaved.

Martin Depken explains his lab's new physics-based approach: "In gene editing, you want to maximize the probability of cutting at the intended site, while minimizing the amount of cutting in the rest of the genome. It is therefore crucial to understand cutting in terms of probabilities. Drawing from experiments in single-molecule physics and structural data, we created a model that can do this. We changed the way in which to describe the gene editing from a binary choice to a complete probabilistic picture."
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First Fully Complete Human Genome Has Been Published After 20 Years
by Jack Dunhill
March 31, 2022

https://www.iflscience.com/health-and-m ... -20-years/

Introduction:
(IFL Science) The first fully complete human genome with no gaps is now available to view for scientists and the public, marking a huge moment for human genetics. Announced in a preprint in June 2021, six papers have now been published in the journal Science. They describe the painstaking work that goes into sequencing an over 6 billion base pair genome, with 200 million added in this new research. The new genome now adds 99 genes likely to code for proteins and 2,000 candidate genes that were previously unknown.

Many will be asking: "wait, didn’t we already sequence the human genome?" In part, yes – in 2000, the Human Genome Sequencing Consortium published their first drafts of the human genome, results that subsequently paved the way for almost every facet of human genetics available today.

The most recent draft of the human genome has been used as a reference since 2013. But weighed down by impractical sequencing techniques, these drafts left out the most complex regions of our DNA, which make up around 8 percent of the total genome. This is because these sequences are highly repetitive and contain many duplicated regions – attempting to put them together in the right places is like trying to complete a jigsaw puzzle where all the pieces are the same shape and have no image on the front. Long gaps and underrepresentation of large, repeating sequences made it so that this genetic material has been excluded for the past 20 years. Scientists had to come up with more accurate methods of sequencing to illuminate the darkest corners of the genome.

“These parts of the human genome that we haven’t been able to study for 20-plus years are important to our understanding of how the genome works, genetic diseases, and human diversity and evolution,” said Karen Miga, assistant professor of biomolecular engineering at UC Santa Cruz, in a statement.

Much like the Human Genome Sequencing Consortium, the new reference genome (called T2T-CHM13) was produced by the Telomere-2-Telomere Consortium, a group of researchers dedicated to finally mapping each chromosome from one telomere to the other. T2T-CHM13 will now be available on UCSC Genome Browser for everyone to enjoy, complimenting the standard human reference genome, GRCh38.
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DNA discovery reveals a critical 'accordion effect' for switching off genes
https://phys.org/news/2022-04-dna-disco ... rdion.html
by Walter and Eliza Hall Institute of Medical Research
WEHI researchers have revealed how an "accordion effect" is critical to switching off genes, in a study that transforms the fundamentals of what we know about gene silencing.  

The finding expands our understanding of how we switch genes on and off to make the different cell types in our bodies, as we develop in the womb.

It also offers a new way to potentially harness gene silencing in the future, to treat or reverse the progression of a broad range of diseases including cancer, congenital and infectious diseases.

Gene silencing is regulated by how tightly DNA is packed into a cell. The findings from a team led by Dr. Andrew Keniry and Professor Marnie Blewitt reveal a new accordion-like trigger that is crucial to the process.
The research is published in Nature Communications.
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Delivering genetic material with MOFs for new therapies
https://phys.org/news/2022-04-genetic-m ... apies.html
by King Abdullah University of Science and Technology

An emerging type of material called a metal-organic framework (MOF) could help improve the delivery of genetic material for treating disease.

MOFs are hybrid materials constructed from metal ions linked by organic molecules. In biomedicine, they have mostly been used as delivery vehicles for small-molecule pharmaceuticals, but now a KAUST-led team has developed a MOF-based system for getting DNA across cell membranes into target cells.

The researchers built their MOFs using a collection of nucleic acid and unnatural amino acid building blocks tethered together by zinc atoms, assembled in a pyramid-like array. They loaded up the resulting materials with single-stranded DNA. The structures protected the genetic cargo from enzymatic degradation and helped ferry the single-stranded DNA into cells, where it ended up inside the nucleus—the cell's inner sanctum where all gene activity takes place.

A critical challenge in gene therapy remains the safe and effective delivery of genetic materials, and most methods in use today are costly, inefficient, imprecise or potentially toxic. The KAUST-devised delivery system could offer an improved means of regulating gene expression and function in people's cells as a way of treating cancer, hemophilia and many more genetic disorders.
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Bioprinting for bone repair improved with gene therapy
https://medicalxpress.com/news/2022-04- ... erapy.html
by A'ndrea Elyse Messer, Pennsylvania State University
Given enough time and energy, the body will heal, but when doctors or engineers intervene, the processes do not always proceed as planned because chemicals that control and facilitate the healing process are missing. Now, an international team of engineers is bioprinting bone along with two growth factor encoding genes that help incorporate the cells and heal defects in the skulls of rats.

"Growth factors are essential for cell growth," said Ibrahim T. Ozbolat, associate professor of engineering science and mechanics. "We use two different genes encoding two different growth factors. These growth factors help stem cells to migrate into the defect area and then help the progenitor cells to convert into bone."

The researchers used gene encoding PDGF-B, platelet derived-growth factor, which encourages cells to multiply and to migrate, and gene encoding BMP-2, bone morphogenetic protein, which improves bone regeneration. They delivered both genes using bioprinting.

"We used a controlled co-delivery release of plasmids from a gene-activated matrix to promote bone repair," the researchers stated in the journal Biomaterials.
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A new era of mitochondrial genome editing has begun
https://phys.org/news/2022-04-era-mitoc ... begun.html
by Institute for Basic Science
Researchers from the Center for Genome Engineering within the Institute for Basic Science developed a new gene-editing platform called transcription activator-like effector-linked deaminases, or TALED. TALEDs are base editors capable of performing A-to-G base conversion in mitochondria. This discovery was a culmination of a decades-long journey to cure human genetic diseases, and TALED can be considered to be the final missing piece of the puzzle in gene-editing technology.

From the identification of the first restriction enzyme in 1968, the invention of polymerase chain reaction (PCR) in 1985, and the demonstration of CRISPR-mediated genome editing in 2013, each new breakthrough discovery in biotechnology further improved our ability to manipulate DNA, the blueprint of life. In particular, the recent development of the CRISPR-Cas system, or "genetic scissors," has allowed for comprehensive genome editing of living cells. This opened new possibilities for treating previously incurable genetic diseases by editing the mutations out of our genome.
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New Gene Editing Technology Offers Fighting Chance Against Grapevine Killer
May 3, 2022

https://www.eurekalert.org/news-releases/951472

Introduction:
(EurekAlert) Scientists at UC Riverside have a shot at eradicating a deadly threat to vineyards posed by the glassy-winged sharpshooter, just as its resistance to insecticide has been growing.

When the half-inch-long flying insect feeds on grapevines, it transmits bacteria that causes Pierce’s Disease. Once infected, a vine is likely to die within three years — a growing problem for California’s $58 billion wine industry. Currently, it can only be controlled with quarantines and increasingly less effective chemical sprays.

New gene-editing technology represents hope for controlling the sharpshooter. Scientists at UC Riverside demonstrated that this technology can make permanent physical changes in the insect. They also showed these changes were passed down to three or more generations of insects.

A paper describing the team’s work has been published in the journal Scientific Reports. (https://www.nature.com/articles/s41598-022-09990-4)

“Our team established, for the first time, genetic approaches to controlling glassy-winged sharpshooters,” said Peter Atkinson, entomologist and paper co-author.
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New method for diagnosing chromosome errors
https://medicalxpress.com/news/2022-05- ... rrors.html
by University of Copenhagen
The most common cause of spontaneous abortions is chromosome defects, but they can be difficult to detect. Researchers from the University of Copenhagen have developed a new method that can make us wiser about how chromosome defects and disease-associated chromosome changes look and how to aid diagnosis.

In Denmark, more and more people are experiencing problems with fertility. The most common cause of spontaneous abortion is chromosome defects. In more than half of the miscarriages that occur during the first 12 weeks, it is because the fetus has a chromosome defect.

Often doctors do not know which chromosome defect is involved. Therefore, it is also difficult to know what the parents can do to complete the pregnancy successfully. However, new research from the University of Copenhagen may help to clarify this.

A newly developed method can characterize chromosomes with an unprecedented level of detail and may help uncover new chromosome errors, which cannot be diagnosed with current methods.
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Researchers use CRISPR technology to modify starches in potatoes
https://phys.org/news/2022-05-crispr-te ... atoes.html
by Kay Ledbetter, Texas A&M University
Humble potatoes are a rich source not only of dietary carbohydrates for humans, but also of starches for numerous industrial applications. Texas A&M AgriLife scientists are learning how to alter the ratio of potatoes' two starch molecules—amylose and amylopectin—to increase both culinary and industrial applications.

For example, waxy potatoes, which are high in amylopectin content, have applications in the production of bioplastics, food additives, adhesives and alcohol.

Two articles recently published in the International Journal of Molecular Sciences and the Plant Cell, Tissue and Organ Culture journals outline how CRISPR technology can advance the uses of the world's largest vegetable crop.

Both papers include the work done by Stephany Toinga, Ph.D., who was a graduate student in the lab of Keerti Rathore, Ph.D., AgriLife Research plant biotechnologist in the Texas A&M Institute for Plant Genomics and Biotechnology and Department of Soil and Crop Sciences. Also co-authoring both papers was Isabel Vales, Ph.D., an AgriLife Research potato breeder in the Texas A&M Department of Horticultural Sciences. Toinga is now a Texas A&M AgriLife Research postdoctoral associate with Vales.

"The information and knowledge we gained from these two studies will help us introduce other desirable traits in this very important crop," Rathore said.
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