How To Correct Genes That Cause High Cholesterol

U.S. researchers have used nanotechnology plus the powerful CRISPR-Cas9 gene-editing tool to turn off a key cholesterol-related gene in mouse liver cells, an advance that could lead to new ways to correct genes that cause high cholesterol and other liver diseasesNanotechnology is the design and manipulation of materials thousands of times smaller than the width of a human hair.

We’ve shown you can make a nanoparticle that can be used to permanently and specifically edit the DNA in the liver of an adult animal,” said study author Daniel Anderson, an associate professor in chemical engineering at the Massachusetts Institute of Technology.

The study, published  in Nature Biotechnology, holds promise for permanently editing genes such as PCSK9, a cholesterol-regulating gene that is already the target of two drugs made by the biotechnology companies Regeneron Pharmaceuticals and Amgen.

In the study, the scientists were trying to develop a safe and efficient way to deliver the components needed for CRISPR-Cas9, a type of molecular scissors that can selectively trim away defective genes and replace them with new stretches of DNA.

The system consists of a DNA-cutting enzyme called Cas9 and a stretch of RNA that guides the cutting enzyme to the correct spot in the genome. Most teams currently use viruses to deliver CRISPR into cells, an approach that is limited because the immune system can develop antibodies to viruses.

To overcome this, the team chemically modified the CRISPR components to protect them from enzymes in the body that would normally break them down. They then inserted this material into nano-scale fat particles and injected them into mice, where they made their way to liver cells.

In tests targeting the PCSK9 gene, the system proved highly effective, . The PCSK9 protein made by this gene was undetectable in the treated mice, eliminating the gene in more than 80 percent of liver cells, which also experienced a 35 percent drop in total cholesterol, the researchers reported.

High levels of cholesterol can clog arteries, causing reduced blood flow that can lead to a heart attack or stroke.

Source: http://news.mit.edu/

The Genome Editor

French biochemist Emmanuelle Charpentier, from the Max Planck Institute in Berlin, was recently awarded the L’oreal-Unesco Prize For Women in Science. The scientist is listed as one of the 100 Most Influential People by Time Magazine. Her discovery, the CRISPR-Cas9, is a gene-editing technology that could revolutionize medical treatments in ways we can only begin to imagine. Marking an incredible leap forward in the long history of genome studies, Emmanuelle Charpentier and her lab partner, scientist Jennifer Doudna, jointly discovered CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats). Behind this name, which sounds like something from a sci-fi novel, is a technology that works like a pair of molecular scissors, allowing to precisely snip the genetic code, letter by letter, along with the programmable enzyme Cas9 able to perform a cut on a double DNA strand. This is a never-before-reached level of precision in genome studies. And one Emmanuelle Charpentier claims could change everyone’s life :

emmanuelle charpentier2

I am excited about the potential of our findings to make a real difference in people’s lives. The discovery demonstrates the relevance of basic research and how it can transform application in bioengineering and biomedicine, said Emmanuelle Charpentier.

While the scientific community agrees that CRISPR-Cas9 is a revolution, the stakes are so high that the question of what’s next seems a difficult one to answer. The technology could be the key to eradicate certain viruses like HIV, haemophilia or Huntington, to screen for cancer genes or to undertake genome engineering. The latter obviously raises moral and ideological issues.

The recent scientific article « CRISPR/Cas9-mediated Gene Editing In Human Tripronuclear Zygotes » published by Protein Cell reports the first experiment on a foetus by a team of scientists in China, and illustrates the potential dangerous consequences (eugenics)  of CRISPR-Cas9 on future generations. Nature & Science refused to publish this experiment, mainly for ethical reasons. This question of ethics reminds us that science and society cannot be isolated from one another.

Source: https://www.mpg.de/
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