Author: Roheeni Saxena

Duchenne muscular dystrophy is one of the most common fatal genetic diseases. It causes muscle degeneration and eventually death due to weakened heart and lung muscles.

Several new experiments published in Science demonstrate that we can now edit the genomes of mice with muscular dystrophy, effectively restoring a large portion of function in the heart and other muscles. These experiments show exciting promise for the use of CRISPR in mammalian gene editing, which could eventually lead to cures for this and other genetic diseases in humans.

Muscular dystrophy is a group of diseases that result in muscle weakness in involuntary and voluntary muscles. Often, this weakness is accompanied by muscle cell death. The specific disorder examined in this study is Duchenne muscular dystrophy, named after the French neurologist who first identified it. It’s a recessive form of dystrophy caused by mutations in the gene dystrophin, which is located on the X-chromosome. Because this is an X-linked recessive disease, it is more common in boys than girls—boys only have one copy of the X chromosome, so if their one copy carries the mutation, they will have the disease.

CRISPR, a genome-editing technology that has been progressing rapidly in the last three years, has just been named Science’s Breakthrough of the Year. CRISPR is a futuristic technique that can be used to edit and manipulate the DNA of any organism—crops, livestock, and even humans. It can allow scientists to control gene expression and selectively turn genes on or off.

In 2015, two significant advances contributed to CRISPR’s status as this year’s Breakthrough technique. The first was the engineering of a “gene drive” in insects that could benefit human health by eliminating pests and the diseases they carry. The second was gene editing performed in human embryos, a process that sounds like something out of a science fiction novel and raises a host of legal and ethical questions about the manipulation of human DNA to create customized offspring.

CRISPR is not only remarkable for its ability to manipulate the DNA of a targeted organism, it is also remarkable because it is an extremely inexpensive and relatively easy technique to use. In terms of the resources it requires, it could be implemented in almost any microbiology lab worldwide.

Many neuroscience studies in animals involve some type of short-term (or acute) manipulation of the brain, followed by behavioral tests. When manipulations of a specific brain circuit are followed by behavioral changes, neuroscientists generally conclude that the circuit contributes to the behavior that's been changed.

But brain circuits are very densely packed and highly interconnected, so it’s hard to manipulate one without influencing others. This makes it particularly challenging to know if the behavioral effects are caused by the part of the brain that was targeted or by some other part that happens to be closely connected to it.

A paper published in Nature shows that short-term alterations and long-term damage can have different effects on behavior. The findings raise a significant caution about the cause-and-effect nature of manipulating the brain and provide a reminder that the brain can sometimes work its way around damage.

The human nervous system is a complex network of cells, all working together. The intense specialization of this network starts during development, when cells must talk to each other to carefully coordinate wiring up neural circuitry.

The wiring relies on the neural cells themselves. They have rounded cell bodies surrounded by short spines called dendrites, and longer tails, called axons. Each neuron only has one axon, which connects to dendrites on other nerve cells.

Sending that axon to the right place—a process called neural pathfinding—is the subject of an entire field of study. Researchers have identified a variety of specialized signaling molecules that instruct neurons on where they should go. It's not always clear, however, how these signaling networks interact to send axons to the right place. A recent paper published in Science helps to clarify some of these unknowns.