Lifeboat Foundation

Genome editing technologies have revolutionized biomedical science, providing a fast and easy way to modify genes. However, the technique allowing scientists to carryout the most precise edits, doesn’t work in cells that are no longer dividing — which includes most neurons in the brain. This technology had limited use in brain research, until now. Research Fellow Jun Nishiyama, M.D., Ph.D., Research Scientist, Takayasu Mikuni, M.D., Ph.D., and Scientific Director, Ryohei Yasuda, Ph.D. at the Max Planck Florida Institute for Neuroscience (MPFI) have developed a new tool that, for the first time, allows precise genome editing in mature neurons, opening up vast new possibilities in neuroscience research.

This novel and powerful tool utilizes the newly discovered gene editing technology of CRISPR-Cas9, a viral defense mechanism originally found in bacteria. When placed inside a cell such as a neuron, the CRISPR-Cas9 system acts to damage DNA in a specifically targeted place. The cell then subsequently repairs this damage using predominantly two opposing methods; one being non-homologous end joining (NHEJ), which tends to be error prone, and homology directed repair (HDR), which is very precise and capable of undergoing specified gene insertions. HDR is the more desired method, allowing researchers flexibility to add, modify, or delete genes depending on the intended purpose.

Coaxing cells in the brain to preferentially make use of the HDR DNA repair mechanism has been rather challenging. HDR was originally thought to only be available as a repair route for actively proliferating cells in the body. When precursor brain cells mature into neurons, they are referred to as post-mitotic or nondividing cells, making the mature brain largely inaccessible to HDR — or so researchers previously thought. The team has now shown that it is possible for post-mitotic neurons of the brain to actively undergo HDR, terming the strategy “vSLENDR (viral mediated single-cell labeling of endogenous proteins by CRISPR-Cas9-mediated homology-directed repair).” The critical key to the success of this process is the combined use of CRISPR-Cas9 and a virus.

Researchers have developed a technique that enables gene editing on neurons — something previously thought to be impossible. This new tool will present amazing new opportunities for neuroscience research.

Technologies designed for editing the human genome are transforming biomedical science and providing us with relatively simple ways to modify and edit genes. However, precision editing has not been possible for cells that have stopped dividing, including mature neurons. This has meant that gene editing has been of limited use in neurological research — until now. Researchers at the Max Planck Florida Institute for Neuroscience (MPFI) have created a new tool that allows, for the first time ever, precise genome editing in mature neurons. This relieves previous constraints and presents amazing new opportunities for neuroscience research.

There’s a difference between editing genes in a person’s somatic cells and germline cells.

Editing somatic cells, which are differentiated (e.g., skin cells) and non-reproductive, impacts them alone. In contrast, editing germline DNA means changes are passed along to the next generation during reproduction. It’s no minor distinction.

Continue reading “When Should We Edit Human Genes? What You Need to Know” »

https://youtube.com/watch?v=o6A9bbDI6fo

The first attempt at human CRISPR gene editing did not occur in a hospital or University or in a clinical trial by some $100 million funded company. Instead, it happened in small cramped room in San Francisco in front of 30 or so people who squeezed in to listen to a talk about how biohackers are making genetic and cellular modification accessible.

Two-thirds of Americans support therapeutic use, but regulators are still stuck in the 1970s.

Should Americans be allowed to edit their DNA to prevent genetic diseases in their children? That question, which once might have sounded like science fiction, is stirring debate as breakthroughs bring the idea closer to reality. Bioethicists and activists, worried about falling down the slippery slope to genetically modified Olympic athletes, are calling for more regulation.

I join this 30 min panel with scientists and a mother with a down syndrome child on Turkish national television to debate genetic editing. I adovcate for allowing genetic editing to improve the human race, despite fears:

Better, stronger, disease-free humans. Editing human DNA could save lives and enhance them. But should we be playing god?
Genes determine our health, looks, the way we function. They’re the ingredients for life. The idea that we could one day change them is an exciting prospect, but also an ethical minefield. As science moves closer towards gene editing, the concern is that it could go too far and even create a new elite group of enhanced humans.

Continue reading “Roundtable: Is human gene editing ethical?” »

Thanks to the gene editing tool CRISPR, the global medical community is on the brink of treating a host of serious diseases, if not eradicating them.

(Phys.org)—A team of researchers from the University of California and the University of Tokyo has found a way to use the CRISPR gene editing technique that does not rely on a virus for delivery. In their paper published in the journal Nature Biomedical Engineering, the group describes the new technique, how well it works and improvements that need to be made to make it a viable gene editing tool.

CRISPR-Cas9 has been in the news a lot lately because it allows researchers to directly edit genes—either disabling unwanted parts or replacing them altogether. But despite many success stories, the technique still suffers from a major deficit that prevents it from being used as a true medical tool—it sometimes makes mistakes. Those mistakes can cause small or big problems for a host depending on what goes wrong. Prior research has suggested that the majority of mistakes are due to delivery problems, which means that a replacement for the virus part of the technique is required. In this new effort, the researchers report that they have discovered just a such a replacement, and it worked so well that it was able to repair a gene mutation in a Duchenne muscular dystrophy mouse model. The team has named the new technique CRISPR-Gold, because a gold nanoparticle was used to deliver the gene editing molecules instead of a virus.

The new package was created by modifying a bit of DNA to cause it to stick to a gold nanoparticle and then a Cas9 protein and also an RNA guide. The package was then coated with a polymer that served as a containment casing—one that also triggered endocytosis (a form of cell transport) and helped the molecules escape endosomes once inside the target cells. The molecules then set to work—the Cas9 cut the target DNA strand, the guide RNA showed what needed to be done and a DNA strand was placed where a mutation had existed. The result was a gene free of a mutation that causes Duchenne muscular dystrophy.

Continue reading “Gold nanoparticle used to replace virus in new CRISPR approach” »

Muscle from a mouse model of Duchenne muscular dystrophy. Fibrous scar tissue is in blue and healthy muscle is in pink. CONBOY LAB AND MURTHY LAB While promising, applications of CRISPR-Cas9 gene editing have so far been limited by the challenges of delivery—namely, how to get all the CRISPR parts to every cell that needs them. In a study published today (October 2) in Nature Biomedical Engineering, researchers have successfully repaired a mutation in the gene for dystrophin in a mouse model of Duchenne muscular dystrophy by injecting a vehicle they call CRISPR-Gold, which contains the Cas9 protein, guide RNA, and donor DNA, all wrapped around a tiny gold ball.

The authors have made “great progress in the gene editing area,” says Tufts University biomedical engineer Qiaobing Xu, who did not participate in the work but penned an accompanying commentary. Because their approach is nonviral, Xu explains, it will minimize the potential off-target effects that result from constant Cas9 activity, which occurs when users deliver the Cas9 template with a viral vector.

Duchenne muscular dystrophy is a degenerative disease of the muscles caused by a lack of the protein dystrophin. In about a third of patients, the gene for dystrophin has small deletions or single base mutations that render it nonfunctional, which makes this gene an excellent candidate for gene editing. Researchers have previously used viral delivery of CRISPR-Cas9 components to delete the mutated exon and achieve clinical improvements in mouse models of the disease.

Continue reading “Nonviral CRISPR Delivery Using Gold Nanoparticles a Success” »