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How Gene Editing is Changing Otolaryngology

by Nikki Kean •

Dr. Welling echoed concerns over the potential downstream risks of the procedure. “If we go off target, it could take decades for the long-term side effects [of gene editing] to unfold,” he warned.

And then he pointed to an even more chilling scenario: “I do believe there will be lot of upsides to this technology, but it is also very accessible [to people with ill intent],” Dr. Welling said. “I know that is one of the concerns the intelligence community [has]—that CRISPR could produce a biologic weapon of mass destruction.”

Financial disclosures: Dr. Staecker disclosed that he is on the surgical advisory board of MedEl. None of the other participants have any financial conflicts to disclose.

Nikki Kean is a freelance medical writer based in New Jersey.

Key Points

  • Dominant deafness genes cannot be corrected with gene replacement strategies, so researchers are turning to gene editing to correct those types of hearing loss.
  • Many practical details regarding gene editing still need to be determined; any treatment for hearing loss would have to be performed during the earliest stages of fetal development.
  • Many bioethicists worry that the rapid pace of gene-editing innovation has occurred without enough discussion about the ethics of the procedure.

What Gene Would You Target First?

  • G. Richard Holt, MD, MSE, MPH: I would say the mutation of GJB2, because it is the most common cause of prelingual deafness, for autosomal recessive and non-syndromic hearing losses. Once you start considering the syndromic hearing losses, it opens up so many more deformities and deficiencies of other organs that, while addressing them would be quite beneficial, it would also be much more difficult. Perhaps [it would be] better to first look at single gene mutations for hearing loss.
  • Lawrence R. Lustig, MD: I would say if we could fix one congenital deafness gene, it should be GJB2 (connexin 26), because that is the most common.
  • Hinrich Staecker, MD, PhD: I would target myosin VII, one of the Usher syndrome genes, because it is the most common dominant gene seen in a cochlear implant population (up to 4%) and presents in prenatal and post-natal forms, so it makes a good potential target.
  • D. Bradley Welling, MD, PhD: Not an easy question to answer. There have been a few animal models that have shown some improvement with the Usher IC gene. Patients with this defect develop hearing loss early.

Landmark Gene-Editing Study Called Into Question

The news that researchers had successfully removed a genetic defect in human embryos using the gene-editing tool CRISPR-Cas9 has recently been called into question. First reported in Nature (2017;548:13-14), the team cited a high success rate (72.4%) at correcting a mutation in the MYBPC3 gene, which causes hypertrophic cardiomyopathy.