in animal models with genetic hearing loss,” said Dr. Chen. “These findings are promising and, when thinking longterm, this technique might eventually have the capability of helping physicians treat hearing loss by correcting genetic mutations in a patient’s cells instead of using drugs or surgery.” Traditionally, gene therapy is the treatment choice for genetic disease by using an engineered virus to deliver the DNA into the cell. However, there are some potential advantages of protein delivery for genome editing that may make it preferable to gene therapy using engineered viruses, which are often difficult to control. Protein delivery allows for a more controlled delivery and may carry a reduced risk of long-term effects. This is because proteins degrade after a certain amount of time in the cell, removing the risk of what the protein may do. This is particularly important for genome editing as it carries the risk of potential off-target effects that could affect unrelated genes. With proteins, the researchers have shown a significantly lower off-target rate following protein delivery than DNA delivery. “When it comes to using a virus for gene therapy, the virus does not degrade,” said Dr. Chen. “With protein delivery for genome editing, however, the proteins enter the cell, perform their function, and then degrade, resulting in a permanent correction of mutations and
less long-term safety concerns. Other applications of protein delivery include the transcription factors to regenerate hair cells. Once the hair cells are regenerated, we will no longer need the transcription factors, again minimizing the long-term safety concerns.” As the researchers continue to explore the use of supercharged proteins and test their applications, they plan to assess several more models of genetic hearing loss that can be tested for hearing recovery in the near future. In addition, they are working on improving the approach and looking at refining components such as ease of use, safety, and overall performance. One of the more specific projects they are working on is determining a safe way to target different cell types at once. Eventually, the researchers believe that protein delivery has applications in other genetic disorders outside of the ear. But for now, their focus is on expanding their research with the hope of one day developing therapies to treat hearing loss. “We want to study the inner ear and find out what’s important for hearing and deafness,” said Dr. Chen. “Having this new technology helps with that and brings us closer to our ultimate goal of restoring hearing for those who may have been born without hearing or have experienced hearing loss throughout their lives.” l
Dr. Yong Tao observes a stained mouse cochlea under the guidance of Dr. Zheng-Yi Chen.
HARVARD Otolaryngology
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