How To Fix Duchenne Muscular Dystrophy

Scientists at the University of California, Berkeley, have engineered a new way to deliver CRISPR-Cas9 gene-editing technology inside cells and have demonstrated in mice that the technology can repair the mutation that causes Duchenne muscular dystrophy, a severe muscle-wasting disease. A new study shows that a single injection of CRISPR-Gold, as the new delivery system is called, into mice with Duchenne muscular dystrophy led to an 18-times-higher correction rate and a two-fold increase in a strength and agility test compared to control groups.

Since 2012, when study co-author Jennifer Doudna, a professor of molecular and cell biology and of chemistry at UC Berkeley, and colleague Emmanuelle Charpentier, of the Max Planck Institute for Infection Biology, repurposed the Cas9 protein to create a cheap, precise and easy-to-use gene editor, researchers have hoped that therapies based on CRISPR-Cas9 would one day revolutionize the treatment of genetic diseases. Yet developing treatments for genetic diseases remains a big challenge in medicine. This is because most genetic diseases can be cured only if the disease-causing gene mutation is corrected back to the normal sequence, and this is impossible to do with conventional therapeutics.

CRISPR/Cas9, however, can correct gene mutations by cutting the mutated DNA and triggering homology-directed DNA repair. However, strategies for safely delivering the necessary components (Cas9, guide RNA that directs Cas9 to a specific gene, and donor DNA) into cells need to be developed before the potential of CRISPR-Cas9-based therapeutics can be realized. A common technique to deliver CRISPR-Cas9 into cells employs viruses, but that technique has a number of complications. CRISPR-Gold does not need viruses.

In the new study, research lead by the laboratories of Berkeley bioengineering professors Niren Murthy and Irina Conboy demonstrated that their novel approach, called CRISPR-Gold because gold nanoparticles are a key component, can deliver Cas9 – the protein that binds and cuts DNA – along with guide RNA and donor DNA into the cells of a living organism to fix a gene mutation.

CRISPR-Gold is the first example of a delivery vehicle that can deliver all of the CRISPR components needed to correct gene mutations, without the use of viruses,” Murthy said.

The study was published in the journal Nature Biomedical Engineering.


Faulty DNA Linked To Fatal Heart Condition Removed From Embryo

Scientists have modified human embryos to remove genetic mutations that cause heart failure in otherwise healthy young people in a landmark demonstration of the controversial procedure. It is the first time that human embryos have had their genomes edited outside China, where researchers have performed a handful of small studies to see whether the approach could prevent inherited diseases from being passed on from one generation to the next.

While none of the research so far has created babies from modified embryos, a move that would be illegal in many countries, the work represents a milestone in scientists’ efforts to master the technique and brings the prospect of human clinical trials one step closer. The work focused on an inherited form of heart disease, but scientists believe the same approach could work for other conditions caused by single gene mutations, such as cystic fibrosis and certain kinds of breast cancer.

This embryo gene correction method, if proven safe, can potentially be used to prevent transmission of genetic disease to future generations,” said Paula Amato, a fertility specialist involved in the US-Korean study at Oregon Health and Science University.

The scientists used a powerful gene editing tool called Crispr-Cas9 to fix mutations in embryos made with the sperm of a man who inherited a heart condition known as hypertrophic cardiomyopathy, or HCM. The disease, which leads to a thickening of the heart’s muscular wall, affects one in 500 people and is a common cause of sudden cardiac arrest in young people. Humans have two copies of every gene, but some diseases are caused by a mutation in only one of the copies. For the study, the scientists recruited a man who carried a single mutant copy of a gene called MYBPC3 which causes HCM.


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.