There are still many disorders and diseases in this world that cannot be cured, and Huntington’s disease (HD) is one of them.
HD is a neurological disorder that causes individuals to lose control of movement, coordination, and cognitive function. HD occurs because of a mutation in the Huntingtin (HTT) gene where a specific codon sequence repeats, creating a long, repetitive sequence that turns into a toxic, expanded protein clump. These clumps form in a part of the brain that regulates movement called the striatum and prevent the neurons in the striatum from functioning properly. As of now, HD still has no cure, but CRISPR gene editing (Clustered Regularly Interspaced Short Palindromic Repeats) might just be the solution.
Dr. Gene Yeo of UC San Diego School of Medicine, along with his team and colleagues from UC Irvine and Johns Hopkins University, researched RNA-targeting CRISPR/Cas13d technology as a way to possibly eliminate HD and its negative effects on the brain. CRISPR gene editing, as its name suggests, enables scientists to “edit” – add, remove, or alter – existing genetic material. The group desired to see if RNA-targeting CRISPR would be able to prevent the creation of the protein clumps that damage the function of the striatum. As we learned in AP Biology, the addition, removal, or substitution of a base of a codon can drastically change the structure and function of a protein. Each codon codes for a specific amino acid, and if multiple codons have changed due to a mutation, it is likely that the protein will fold differently than it is supposed to and will lose its function.
Yeo and his team desired to develop an effective therapy for HD, hoping to stop the formation of toxic protein clumps and alter the course of the disease. However, they did not want to create permanent changes in the human genome as a precaution. The team instead engineered a therapy that alters the RNA that turns into the protein clumps. They conducted testing on mice and found that RNA-targeting CRISPR therapy reduced toxic protein levels in a mouse with HD, improving motor coordination. In connection with the molecular genetics unit in AP Biology, since the RNA that causes HD is altered, the protein that is translated will change since different amino acids correspond to different codons.
Further testing will be necessary to confirm the benefits of this therapeutic strategy, but CRISPR does look like a promising medical treatment for HD and many other diseases in the future.