Summary of Harvard Researchers Design “Mini Gene” Therapy for Severe Genetic Disease:
Researchers have developed a “mini gene” therapy that shows promise for treating Usher Syndrome type 1F, a rare genetic disorder that causes deafness and vision loss. The treatment was tested on mice and increased the production of a crucial protein responsible for the progressive vision loss associated with the syndrome. The mini gene was designed to replace the mutated gene in Usher 1F. While it successfully treated deafness in the mouse model, the researchers are more interested in its potential for treating blindness. The researchers plan to continue testing the mini gene in other animal models and eventually in humans.
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New “Mini Gene” Gene Therapy Shows Promise in Treating Usher Syndrome Type 1F
Usher Syndrome type 1F is a rare genetic disorder that combines deafness, impaired balance, and progressive vision loss. The condition currently has no cure. However, researchers from Harvard Medical School, Massachusetts Eye and Ear, and The Ohio State University have developed a gene therapy for Usher 1F using a “mini gene” that has shown promise in mice as a potential treatment for the debilitating syndrome.
Mini Gene Therapy: A Promising First Step
The “mini gene” developed by the team of researchers has been designed to replace the mutated gene responsible for Usher 1F. The mutated gene impairs the production of a crucial protein required for auditory and visual systems to function correctly. The therapy increased the output of the missing protein in mice, enabling the hair cells to sense sound and restoring hearing. Promisingly, the same approach may help prevent blindness related to the condition.
Co-senior author Artur Indzhykulian, HMS assistant professor of otolaryngology–head and neck surgery at Mass Eye and Ear, explained: “Patients with Usher 1F are born with profound hearing loss and progressive vision loss, and so far we have been able to offer very few solutions to these families.” The researchers plan to continue testing the mini gene in other animal models and eventually in humans.
Applying Expertise to a New Challenge
Children with Usher Syndrome are typically born deaf or with severely impaired hearing, lack balance, and lose vision over time as the retina deteriorates. Researchers in the Corey lab at Harvard Medical School have long been studying protocadherin-15’s role in the inner ear, mainly how it helps sensory receptors convert sounds into electrical signals so the brain can detect sound.
The researchers used the knowledge of the protein’s structure to design a mini gene therapy, replacing the DNA that codes for protocadherin-15 into a cell, thus enabling the cell to begin making the protein. The researchers had to develop the mini gene therapy because the protocadherin-15 protein is too big for the typical viral capsule that transports genetic material into the cell.
The team created a shortened version of the protein, truncating sections of the original DNA sequence, ultimately achieving the perfect mini gene that could fit inside the viral capsule to transport the genetic material.
Positive Results in Mice
After extensive testing of the mini gene therapy on mice, the researchers have seen promising results, using the mini gene therapy to help the hair cells produce a shortened version of protocadherin-15, binding it to cadherin-23, opening ion channels, and sending signals to the brain, restoring hearing in deaf mice. This success has encouraged the researchers to proceed with their trials.
Next Steps: More Testing and Considerable Hopes
The researchers plan to test further mice and zebrafish, which experience rapid vision loss when protocadherin-15 is not produced in the retina. If successful, they plan to try the mini gene therapy in primates and humans.
While mini-gene therapy has shown great promise, it’s important to remember that the research is still in the early stages. In the meantime, those with Usher 1F must continue to manage the disorder in other ways. However, with the results of this study, there is hope for a cure, bringing relief to countless people struggling with this debilitating condition.
