A research team recently used the powerful genomic editing tool CRISPR-Cas9 in a study to eradicate autistic behavioral traits in mice. The experiment included normal mice, and mice with fragile X syndrome, a common single-gene form of autism. The mice with this disorder display exaggerated repetitive behavior that is character of autism, such as repetitive jumping and digging.
The researchers measured the amount of digging by putting marbles in a container of shavings with the mice and observed how visible the marbles were over the course of time. Mice with fragile X syndrome dig obsessively in attempts of covering all the marbles.
After treating the mice with an intracranial injection of CRISPR, researchers found that less of the marbles were hidden by the shavings, indicating a decrease in obsessive digging.
CRISPR associated protein 9 (Cas9) is the specific enzyme responsible for making specific cuts to DNA, often referred to as ‘molecular scissors’. In a technique they created called CRISPR-Gold, researchers at the University of California, Berkeley used gold nanoparticles in this experiment to administer Cas9 to the brain. After being injected directly into the striatum (brain region dictating habit formation) of the mice, Cas9 can cut out specific segments of DNA in a manner that eliminates genes associated with autism. The research team is currently working to develop a CRISPR-Gold system that allows injection to the spinal cord rather than the brain, avoiding the need to open the skull.
“This is the first time anyone had ever shown that with non-viral delivery” – Niren Murthy, CRISPR-Gold inventor
This study was the first instance in which Cas9 was able to successfully knockout a gene on the brain to demonstrate therapeutic effects. Previous research has used viruses to insert genes for Cas9 into neurons, however continued expression of the Cas9 enzyme leads to random cutting of other genes. CRISPR-Gold manages to transport the Cas9 enzyme and guiding RNA directly to the neurons where it cuts in a controlled manner.
There are many forms of autism, with a broad spectrum of magnitudes ranging from mild difficulty with social interactions to being fully nonverbal. 1 in 59 suffer from autism spectrum disorder (ASD), whereas only 1 in every 4,000 boys and 6,000 girls suffer from fragile X syndrome. While there appear to be many genetic factors contributing to the ASD, single-gene disorders like fragile X syndrome provide a simplified way to explore treatments that can potentially eradicate symptoms of autism.