Researchers at Oregon State University and Oregon Health & Science University have developed a promising, first-of-its-kind messenger RNA therapy for ovarian cancer as well as cachexia, a muscle-wasting condition associated with cancer and other chronic illnesses.
The treatment is based on the same principles used in SARS-CoV-2 vaccines, and the scientists say mRNA technology, though still in its infancy in terms of therapeutic application, holds tremendous clinical potential for the management of disease. Messenger RNA carries instructions to cells regarding the manufacture of proteins.
The findings, achieved through a mouse model and published today in the journal Small, are important because ovarian cancer is a particularly deadly form of cancer, with a five-year survival rate of less than 30% if it has spread beyond the ovaries.
Gene-edited tomato can fight cancer and heart disease
13th September 2022
U.S. regulators have approved a new purple tomato, genetically engineered to be packed with antioxidants and anthocyanins. The fruit will go on sale in 2023.
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U.S. home growers should be able to purchase seeds and grow the enhanced tomato from spring 2023.
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A study published in the peer-reviewed journal Nature Biotechnology showed that mice fed a diet supplemented with the high-anthocyanin tomatoes achieved a significant extension of lifespan.
Five people with severe autoimmune disease have become the first in the world to receive a groundbreaking therapy that uses genetically altered cells to drive the illness into remission.
The four women and one man, aged 18 to 24, received transfusions of modified immune cells to treat severe lupus, an autoimmune disease that can cause life-threatening damage to the heart, lungs, brain and kidneys.
Researchers from the Institute of Biotechnology, University of Helsinki, pioneers in identifying the first patient mutations on the NFkB1-gene, cooperated with international clinicians to identify and characterize a plethora of unreported NFKB1 variants on patients with immune system related illnesses.
In many cases, the identification of a genetic defect in a patient is of great importance for the treatment and prognosis of patients with rare diseases. NFKB1, a transcription factor, causes changes in gene expression and is activated by stress and immune related signaling pathways. Mutations in the NFkB1 have previously been linked to common variable immune deficiency (CVID).
Two new studies published in Frontiers in Immunology may bring further relief for patients with hereditary gene defects in their immune systems.
"These studies have significantly expanded the associations of NFKB1 variants to immune system dysfunction—the connections which we first reportedin 2017," says research director Markku Varjosalo from the Institute of Biotechnology, University of Helsinki
Researchers identified two new NFKB1 variants in two families suffering from common variable immune deficiency. Both identified NFKB1 variants caused reduced expression of the NFKB1 protein and lead to an altered gene expression and increased inflammation response in patient cells. Interaction analysis again showed loss of interactions for one of the variants but not the other.
Scientists have engineered mosquitoes that slow the growth of malaria-causing parasites in their gut, preventing transmission of the disease to humans.
The genetic modification causes mosquitoes to produce compounds in their guts that stunt the growth of parasites, meaning they are unlikely to reach the mosquitoes' salivary glands and be passed on in a bite before the insects die.
So far, the technique has been shown to dramatically reduce the possibility of malaria spread in a lab setting, but if proven safe and effective in real-world settings it could offer a powerful new tool to help eliminate malaria.
The innovation, by researchers from the Transmission:Zero team at Imperial College London, is designed so it can be coupled with existing "gene drive" technology to spread the modification and drastically cut malaria transmission. The team is looking towards field trials, but will thoroughly test the safety of the new modification before combining it with a gene drive for real-world tests.
Collaborators from the Institute for Disease Modeling at the Bill and Melinda Gates Foundation also developed a model that, for the first time, can assess the impact of such modifications if used in a variety of African settings. They found that the modification developed by the Transmission:Zero team could be a powerful tool for bringing down cases of malaria even where transmission is high.
The results of the modification technology in the lab and the modeling are published today in Science Advances.
Duke University researchers have developed an RNA-based editing tool that targets individual cells, rather than genes. It is capable of precisely targeting any type of cell and selectively adding any protein of interest.
Researchers said the tool could enable modifying very specific cells and cell functions to manage disease.
Using an RNA-based probe, a team led by neurobiologist Z. Josh Huang, Ph.D. and postdoctoral researcher Yongjun Qian, Ph.D. demonstrated they can introduce into cells fluorescent tags to label specific types of brain tissue; a light-sensitive on/off switch to silence or activate neurons of their choosing; and even a self-destruct enzyme to precisely expunge some cells but not others. The work appears Oct. 5 in Nature.
Their selective cell monitoring and control system relies on the ADAR enzyme, which is found in every animal's cells. While these are early days for CellREADR (Cell access through RNA sensing by Endogenous ADAR), the possible applications appear to be endless, Huang said, as is its potential to work across the animal kingdom.
"We're excited because this provides a simplified, scalable and generalizable technology to monitor and manipulate all cell types in any animal," Huang said. "We could actually modify specific types of cell function to manage diseases, regardless of their initial genetic predisposition," he said. "That's not possible with current therapies or medicine."
A team of researchers at Northwestern University has devised a new platform for gene editing that could inform the future application of a near-limitless library of CRISPR-based therapeutics.
Using chemical design and synthesis, the team brought together the Nobel-prize winning technology with therapeutic technology born in their own lab to overcome a critical limitation of CRISPR. Specifically, the groundbreaking work provides a system to deliver the cargo required for generating the gene editing machine known as CRISPR-Cas9. The team developed a way to transform the Cas-9 protein into a spherical nucleic acid (SNA) and load it with critical components as required to access a broad range of tissue and cell types, as well as the intracellular compartments required for gene editing.
The research, published today in a paper titled "CRISPR Spherical Nucleic Acids," in the publication Journal of the American Chemical Society, and shows how CRISPR SNAs can be delivered across the cell membrane and into the nucleus while also retaining bioactivity and gene editing capabilities.
The work builds on a 25-year effort steered by nanotechnology pioneer Chad A. Mirkin, who led the study, to uncover the properties of SNAs and the factors that distinguish them from their well-known linear cousin, the blueprint of life. He is famed for his invention of SNAs, structures typically comprised of spherical nanoparticles densely covered with DNA or RNA, giving them chemical and physical properties radically different from those forms of nucleic acids found in nature.
When searching for the causes of illnesses and developing new treatments, it is absolutely vital to have a precise understanding of the genetic fundamentals. Würzburg researchers have devised a new technique for this purpose.
Pathological processes are usually characterized by altered gene activity in the cells affected. So, gaining an accurate picture of gene activity can provide the key to the development of new, targeted therapies. Whether these therapies then work as we would want them to can also be verified by looking at genes and the processes they initiate.
It is no wonder that research is focused on methods and techniques that provide detailed information about the genetic activity of individual cells. A research team at the University of Würzburg (JMU) has now developed a technique that is a significant improvement on the methods used to date. Scientists from the Institute for Molecular Infection Biology (IMIB) and the Helmholtz Institute for RNA-based Infection Research (HIRI) were involved. They have presented the results of their work in the current issue of the journal Nucleic Acids Research.
Analysis of a synthetic transcriptome
"We have developed a technique that can be used to analyze the translational landscape of a fully customizable synthetic transcriptome, in other words one outside the cell," is how Jörg Vogel explains the central outcome of the study. Vogel heads the Institute for Molecular Infection Biology at JMU and is also the Director of HIRI as well as the principal author of the study. The new technique has been given the scientific name INRI-seq, which is short for in vitro Ribo-seq.
Hereditary primary haemochromatosis is one of the most common inborn errors of metabolism in Europe. In this disorder, also known as iron storage disease, the body is overloaded with iron. The excess iron accumulates in organs and tissues and leads to slowly progressive damage to the liver, heart, pancreas, pituitary gland and joints. This can lead to changes in the heart muscle (cardiomyopathies) or diabetes mellitus (bronchial diabetes), and even to scarring of the liver tissue (liver cirrhosis) and liver cancer.
The cause is a genetic defect that disrupts the regulation of iron absorption via the mucous membrane of the small intestine. A research team led by Professor Dr. Michael Ott and Dr. Simon Krooss from the Department of Gastroenterology, Hepatology and Endocrinology at the Hannover Medical School (MHH) has now found a way to treat the hereditary disease with the help of targeted gene correction. The work has been published in the journal Nature Communications.
Control of iron absorption defective
"In most cases, iron storage disease is due to a defect in the haemochromatosis gene HFE, which is located on chromosome 6," says Professor Ott. It only occurs in people who have inherited this defect from both parents, i.e. who do not have a "healthy" gene to compensate. In more than 80% of those affected, a certain change, called the C282Y mutation, is found in both copies of the HFE gene. This leads to the replacement of an amino acid—i.e. a protein building block—in the HFE protein.
Johns Hopkins Medicine researchers say they have successfully used a cell's natural process for making proteins to "slide" genetic instructions into a cell and produce critical proteins missing from those cells. If further studies verify their proof-of-concept results, the scientists may have a new method for targeting specific cell types for a variety of disorders that could be treated with gene therapies. Such disorders include neurodegenerative diseases that affect the brain, including Alzheimer's disease, forms of blindness and some cancers.
For those looking to develop treatments for diseases where cells lack a specific protein, it's critical to precisely target the cell causing the disease in each structure, such as the brain, to safely kickstart the protein-making process of certain genes, says Seth Blackshaw, Ph.D., professor of neuroscience in the Sol Snyder Department of Neuroscience and member of the Institute for Cell Engineering at the Johns Hopkins University School of Medicine. Therapies that don't precisely target diseased cells can have unintended effects in other healthy cells, he adds.
Two methods currently used to deliver protein-making packages into cells vary widely in their effectiveness in both animal models and people. "We wanted to develop a gene expression delivery tool that's broadly useful in both preclinical and clinical models," says Blackshaw.
One current method of sending biochemical packages involves so-called "mini promoters" that direct the expression (protein-making process) of certain stretches of DNA. Blackshaw says this method often fails to express genes in the right cell type.
10 years ago we saw a breakthrough in modern biology.
An American scientist discovered that manipulation of the Cas9 protein resulted in a gene technology worthy of a sci-fi film: CRISPR.
Think of it as a pair of molecular scissors capable of cutting and editing the DNA of humans, animals, plants, bacteria and viruses.
The potential is huge and covers anything from deleting hereditary diseases to producing crops able to withstand climate change.
However, like any other new technology, CRISPR has had its challenges. One of the main challenges has been to make the technology as effective as possible and to make sure the scissors only cut where we want them to.
'We have described new mechanisms behind CRISPR'
Two new studies from the University of Copenhagen conducted together with researchers from Aarhus University can help solve these problems.
"We have described new mechanisms behind CRISPR," says Professor of Bioinformatics Jan Gorodkin from the Department of Veterinary and Animal Sciences.
For several years now, the CRISPR/Cas9 gene scissors have been causing a sensation in science and medicine. This new tool of molecular biology has its origins in an ancient bacterial immune system. It protects bacteria from attack by so-called phages (viruses that infect bacteria).
Researchers from the Institute of Structural Biology at the University Hospital Bonn (UKB) and the Medical Faculty of the University of Bonn, in cooperation with the partner University of St Andrews in Scotland and the European Molecular Biology Laboratory in Hamburg, have now discovered a new function of the gene scissors. The study was published in Nature.
Bacteria and phages have been engaged in a life-and-death struggle on Earth since time immemorial. When an attacking phage injects its genetic material into a bacterium, it is forced to produce new phages, which in turn infect more bacteria. Some bacteria have evolved the CRISPR system in response. With this bacterial immune system, the phage genetic material is recognized and destroyed.
Possibly a very stupid statement but I feel genetic engineering is one of those future technologies which will never be a huge thing.
By the time genetic engineering is ready I feel we'll already have AGI and there'll be more efficient ways to increase our intelligence such as brain computer interfaces. Generally the way we'll enhance ourselves will be through non-biological means.
Gene editing company hopes to bring dodo ‘back to life’
Tue 31 Jan 2023 10.31 EST
The dodo, a Mauritian bird last seen in the 17th century, will be brought back to at least a semblance of life if attempts by a gene editing company are successful.
Gene editing techniques now exist that allow scientists to mine the dodo genome for key traits that they believe they can then effectively reassemble within the body of a living relative.
Dodos are most closely related to pigeons, according to sequencing of the proverbially dead bird’s genome.
The scientists in question said their work, beyond providing an insight into the extinct dodo’s existence, could help inform the conservation of rare species that are not yet extinct. However, there is a fierce debate among biologists over whether this sort of research should be pursued.
Colossal Biosciences, the gene editing company involved, has already embarked on projects to revive the woolly mammoth and the thylacine. But the dodo would be its first bird, which is significant as it means changing the gene editing technique to accommodate an external egg.
An article published today in the journal Science indicates that a substantial proportion of Americans are willing to use an essentially unregulated reproductive genetic technology to increase the chances of having a baby who is someday admitted to a top-100 ranked college.
Survey respondents with college degrees, as well as those under 35 years of age—prime child-bearing age—were more willing to use polygenic embryo screening in conjunction with in vitro fertilization (IVF) to do so, the study found.
Polygenic indexes (also called polygenic risk scores) can provide an estimate of disease risk—or other traits—based on an individual's genes. Private companies working with IVF clinics offer the service to patients who can select an embryo with a lower chance of developing diabetes, cancer, heart disease, inflammatory bowel disease, Alzheimer's disease or schizophrenia as an adult.
Hijacking our cells' enzymes to eliminate disease-causing proteins
by University of Illinois at Chicago
By studying how enzymes move from one membrane compartment to another inside a cell, scientists at the University of Illinois Chicago have figured out a way to better target cellular proteins, which play a role in many diseases.
Their findings, published in a Cell Reports paper titled "Palmitoylation and PDE6δ regulate membrane-compartment-specific substrate ubiquitylation and degradation," have implications for developing new therapies.
Lead author Shafi Kuchay, assistant professor of biochemistry and molecular genetics in the College of Medicine and member of the University of Illinois Cancer Center at UIC, said that most common drugs work by targeting proteins that are located at the membranes of cells. Many of these proteins can cause diseases by being overly active. Unfortunately, most currently available drugs just block the activity of the harmful proteins, and while they are helpful in the short term, resistance to the drugs can develop over time.
"We are interested in understanding how and why ubiquitin ligase enzymes, which can naturally degrade proteins, move around the cellular compartments and are able to find very specific proteins to degrade," Kuchay said. "We want to leverage this natural process so we can repurpose ubiquitin ligase enzymes to completely remove problematic proteins that lead to diseases, as opposed to just blocking their activity."
The researchers looked at a ubiquitin ligase enzyme named FBXL2, known to degrade proteins at various cellular membrane compartments. They found that by attaching or detaching a fat molecule or lipid to FBXL2—a process called palmitoylation and de-palmitoylation—they could direct where the FBXL2 went.
A team of biologists from Rothamsted Research, the University of Bristol and Curtis Analytics Limited—all in the U.K.—has used the CRISPR-Cas9 gene editing system to knock out the asparagine gene in wheat grown in real-world conditions—part of an effort reduce the risk of cancer in people who consume food made from plants that produce the compound. The team has published an article describing their work in Plant Biotechnology Journal.
Scientists have known for a long time that many types of plants and animals produce an amino acid called asparagine, which by itself is not considered harmful. When it is heated to a certain degree, a chemical reaction occurs that results in the production of acrylamide, a carcinogen. Prior research has shown that it can increase the risk of developing cancers in mice.
Asparagine is produced by cows and winds up in both milk and meat, and also by many types of food fish. It is also produced by many crop plants, such as potatoes and asparagus and by many whole grains, including wheat. Medical scientists have not been able to verify whether baked products such as bread have levels of acrylamide high enough to pose a health risk but would like to see levels of asparagine in flour reduced to ensure safety.
Prior research has shown that the amount of asparagine in plants varies depending on weather conditions as they grow. In this new effort, the team in the U.K. sought to reduce the amount produced in wheat plants independent of weather conditions.
Back in 2021, the same research team used CRISPR-Cas9 to remove the gene responsible for the generation of the amino acid in wheat plants to reduce the amount of acrylamide created during baking. They tested their work by growing wheat samples in a greenhouse and measuring asparagine levels after the plants grew to full maturity.
