Neuron with mHtt inclusion

Neurons transfected with a disease-associated version of huntingtin

Huntington’s disease is a neurological disorder that affects the basal ganglia and cerebral cortex of the brain. These areas of the brain are associated with movement, learning, thinking, planning, motivation, and emotion. Huntington’s disease is caused by a single mutation in the huntingtin (HTT) gene, afflicting more than 200,000 people worldwide and 30,000 in the United States. There was believed to be no cure, however, novel research regarding CRISPR gene editing is giving those who suffer from this condition new hope. 

Identifying the problem (and connection to AP Bio)

“Our cells have a hard time copying repetitive DNA, and these copying errors can cause repetitive sequences to grow longer with each generation,” (Gene Yeo, PhD). 

Huntington’s disease is caused by repetitive and damaging sequences in the HTT gene. Within the cell cycle, in order for the cell to divide into two daughter cells during mitosis, the cell’s DNA must be replicated in the synthesis phase. In Huntington’s disease, the damage done to the HTT gene is carried through the synthesis phase, causing everlasting effects on future generations of cells. These repeated genes amass to many times their normal length and result in toxic clumps which aggravate the striatum of the brain which is important in regulating movement; thereby leading to Huntington’s Disease. 

Inventing a solution

CRISPR is a tool that edits genomes by precisely cutting DNA and then letting natural DNA repair processes take over. The system consists of two parts: the Cas9 enzyme and a guide RNA. CRISPR illustration gif animation 1In this new study, Gene Yeo and his team of researchers at the University of California San Diego School of Medicine are using RNA-targeting CRISPR/Cas13d technology to develop a new therapeutic strategy that specifically eliminates toxic RNA that causes HD. Yeo delivered the CRISPR therapy through viral vehicles to neuronal cultures grown from the stem cells of an individual with Huntington’s syndrome. His team has found that the approach not only targeted and destroyed mutant RNA molecules but also cleared out toxic protein buildup without disrupting other genes. 

Predictions for the future

Black-mouse-in-purple-gloved-hands-2Yeo’s team collaborated with Wenzhen Duan’s team at Johns Hopkins to conduct preclinical testing in mice. They found that the CRISPR therapy improved motor coordination, attenuated striatal degradation and reduced toxic protein levels in a mouse model of HD. The therapy lasted for at least 8 months and caused minimal effects on other RNA molecules. Although a mice’s anatomy is nowhere near as complex as a human’s, this new research gives incredible insight into the future that CRISPR holds and how impactful its use can be.

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