The Promise of Gene Editing
“Gene editing is now much simpler and better than it has ever been. Even though we have tried to edit genes for a long time, the relatively recent discovery of the CRISPR-Cas technology, in which we can discreetly edit parts of the gene, is very exciting,” said D. Bradley Welling, MD, PhD, the Walter Augustus LeCompte Professor and chair of the department of otolaryngology at Harvard Medical School in Boston, and editor of ENTtoday’s sister publication Laryngoscope Investigative Otolaryngology.
“The CRISPR technique can now target messenger RNA [mRNA], which theoretically could solve a lot of our problems, but there are a lot of practical details that would have to be worked out, at least in the human ear,” said Lawrence R. Lustig, MD, Howard W. Smith Professor and chair of the department of otolaryngology–head and neck surgery at Columbia University College of Physicians and Surgeons in New York City. He noted, for example, that any treatment for hearing loss would have to be performed in the earliest stages of fetal development; once degenerative hearing loss begins, there is no way to reverse it.
To test the viability of early treatment, Dr. Lustig and his colleagues are using adeno-associate virus type 1 (AAV1) vectors very early in the mouse life cycle, day 1 after birth, “which actually translates into a human baby in utero,” he said. In one study, his team used gene replacement therapy to restore hearing in a mouse model by using the AAV1 to deliver vesicular glutamate transporter-3 (VGLUT3) cells into the cochlea of impaired mice. Within two weeks of AAV1-VGLUT3 delivery, the newborn mice had restoration of their auditory brainstem response and partial rescue of the startle response (Neuron. 2012;75:283–293).