Lifeboat Foundation

A breakthrough in synthetic biology could shed new light on mechanisms controlling the most basic processes of life.

Gene editing has shown great promise as a non-heritable way to treat a wide range of conditions, including many genetic diseases and more recently, even COVID-19. But could a version of the CRISPR gene-editing tool also help deliver long-lasting pain relief without the risk of addiction associated with prescription opioid drugs?

In work recently published in the journal Science Translational Medicine, researchers demonstrated in mice that a modified version of the CRISPR system can be used to “turn off” a gene in critical neurons to block the transmission of pain signals [1]. While much more study is needed and the approach is still far from being tested in people, the findings suggest that this new CRISPR-based strategy could form the basis for a whole new way to manage chronic pain.

This novel approach to treating chronic pain occurred to Ana Moreno, the study’s first author, when she was a Ph.D. student in the NIH-supported lab of Prashant Mali, University of California, San Diego. Mali had been studying a wide range of novel gene-and cell-based therapeutics. While reading up on both, Moreno landed on a paper about a mutation in a gene that encodes a pain-enhancing protein in spinal neurons called NaV1.7.

**Five years ago, scientists created a single-celled synthetic organism that, with only 473 genes, was the simplest living cell ever known.** However, this bacteria-like organism behaved strangely when growing and dividing, producing cells with wildly different shapes and sizes.

Now, scientists have identified seven genes that can be added to tame the cells’ unruly nature, causing them to neatly divide into uniform orbs. This achievement, a collaboration between the J. Craig Venter Institute (JCVI), the National Institute of Standards and Technology (NIST) and the Massachusetts Institute of Technology (MIT) Center for Bits and Atoms, was described in the journal Cell.

Identifying these genes is an important step toward engineering synthetic cells that do useful things. Such cells could act as small factories that produce drugs, foods and fuels; detect disease and produce drugs to treat it while living inside the body; and function as tiny computers.

Continue reading “Scientists create simple synthetic cell that grows and divides normally” »

Age-related macular degeneration (AMD), which leads to a loss of central vision, is the most frequent cause of blindness in adults 50 years of age or older, affecting an estimated 196 million people worldwide. There is no cure, though treatment can slow the onset and preserve some vision.

Recently, however, researchers at the University of Rochester have made an important breakthrough in the quest for an AMD cure. Their first three-dimensional (3D) lab model mimics the part of the human retina affected in macular degeneration.

Their model combines stem cell-derived retinal tissue and vascular networks from human patients with bioengineered synthetic materials in a three-dimensional “matrix.” Notably, using patient-derived 3D retinal tissue allowed the researchers to investigate the underlying mechanisms involved in advanced neovascular macular degeneration, the wet form of macular degeneration, which is the more debilitating and blinding form of the disease.

The genome editing technology CRISPR has emerged as a powerful new tool that can change the way we treat disease. The challenge when altering the genetics of our cells, however, is how to do it safely, effectively, and specifically targeted to the gene, tissue and organ that needs treatment. Scientists at Tufts University and the Broad Institute of Harvard and MIT have developed unique nanoparticles comprised of lipids—fat molecules—that can package and deliver gene editing machinery specifically to the liver. In a study published today in the Proceedings of the National Academy of Sciences, they have shown that they can use the lipid nanoparticles (LNPs) to efficiently deliver the CRISPR machinery into the liver of mice, resulting in specific genome editing and the reduction of blood cholesterol levels by as much as 57%—a reduction that can last for at least several months with just one shot.

The problem of high cholesterol plagues more than 29 million Americans, according to the Centers for Disease Control and Prevention. The condition is complex and can originate from multiple genes as well as nutritional and lifestyle choices, so it is not easy to treat. The Tufts and Broad researchers, however, have modified one gene that could provide a protective effect against elevated cholesterol if it can be shut down by gene editing.

The gene that the researchers focused on codes for the angiopoietin-like 3 enzyme (Angptl3). That enzyme tamps down the activity of other enzymes—lipases—that help break down cholesterol. If researchers can knock out the Angptl3 gene, they can let the lipases do their work and reduce levels of cholesterol in the blood. It turns out that some lucky people have a natural mutation in their Angptl3 gene, leading to consistently low levels of triglycerides and low-density lipoprotein (LDL) cholesterol, commonly called “bad” cholesterol, in their bloodstream without any known clinical downsides.

Now scientists are hoping to use the knowledge about CRISPR systems to engineering phages to destroy dangerous bacteria.

As the world fights the SARS-CoV-2 virus causing the COVID-19 pandemic, another group of dangerous pathogens looms in the background.

Using an improved version of the gene editing tool CRISPR/Cas9, researchers knocked out up to twelve genes in plants in a single blow. Until now, this had only been possible for single or small groups of genes. The approach was developed by researchers at Martin Luther University Halle-Wittenberg (MLU) and the Leibniz Institute of Plant Biochemistry (IPB). The method makes it easier to investigate the interaction of various genes. The study appeared in The Plant Journal.

The inheritance of traits in plants is rarely as simple and straightforward as Gregor Mendel described. The monk, whose experiments in the 19th century on trait inheritance in peas laid the foundation of genetics, in fact got lucky. “In the traits that Mendel studied, the rule that only one gene determines a specific trait, for example the color of the peas, happened to apply,” says plant geneticist Dr. Johannes Stuttmann from the Institute of Biology at MLU. According to the researcher, things are often much more complicated. Frequently there are different genes that, through their interaction with one another, result in certain traits or they are partly redundant, in other words they result in the same trait. In this case, when only one of these genes is switched off, the effects are not visible in the plants.

The scientists at MLU and IPB have now developed a way to study this complex phenomenon in a more targeted way by improving CRISPR/Cas9. These gene editing tools can be used to cut the DNA of organisms at specific sites. The team built on the work of biologist Dr. Sylvestre Marillonnet who developed an optimized building block for the CRISPR/Cas9 system at the IPB. “This building block helps to produce significantly more Cas9 enzyme in the plants, which acts as a scissor for the genetic material,” explains Stuttmann. The researchers added up to 24 different guide RNAs which guide the scissor enzyme to the desired locations in the genetic material. Experiments on thale cress (Arabidopsis thaliana) and the wild tobacco plant Nicotiana benthamiana proved that the approach works. Up to eight genes could be switched off simultaneously in the tobacco plants while, in the thale cress, up to twelve genes could be switched off in some cases.

In the case of DMD caused by a duplication mutation, CRISPR can simply snip away the harmful duplicate gene, which is much simpler than delivering a new gene or replacing the old.

For the first time in a live animal, researchers have successfully reversed a gene mutation, called a “duplication mutation,” by gene editing.

Summary: A new genetic engineering strategy significantly reduces levels of tau in animal models of Alzheimer’s disease. The treatment, which involves a single injection, appears to have long-last effects.

Source: Mass General.

Researchers have used a genetic engineering strategy to dramatically reduce levels of tau–a key protein that accumulates and becomes tangled in the brain during the development of Alzheimer’s disease–in an animal model of the condition.