Gene Therapy Strategies for Usher Syndrome Type 1B

  • David S. WilliamsEmail author
  • Vanda S. Lopes
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 723)


Usher syndrome type 1B (Usher 1B) is an inherited deaf-blindness disorder, caused by mutations in the MYO7A gene. Newborns with Usher 1 are readily identified due to their congenital profound deafness. Thus, they are prime candidates for gene therapy to treat their ensuing progressive blindness. MYO7A functions in both the retinal pigment epithelium (RPE) and photoreceptor cells, and Myo7a-null mice demonstrate mutant phenotypes in both cell types. Preclinical studies have tested the efficacy of correcting these mutant phenotypes by delivering MYO7A cDNA with different lentiviral and adeno-associated viral vectors, following subretinal injections. Lentiviruses successfully delivered functional MYO7A to both RPE and photoreceptor cells, although the integrating viruses resulted in some variation in expression level, and thus efficacy, from cell to cell. The size of MYO7A cDNA is too large to be packaged by adeno-associated virus (AAV) without fragmentation; however, AAV delivery was nevertheless found to correct the mutant phenotypes. Therefore, although each viral approach has its own limitation, both vectors work to restore functional MYO7A in the mouse retina, and are realistic candidates for use in preventing blindness in Usher 1B patients.


Adeno-associated virus Gene therapy Lentivirus Melanosome MYO7A Photoreceptor Opsin Retinal pigment epithelium Usher syndrome 



We are grateful to Drs. Samuel Jacobson, Bill Hauswirth, Katie Binley, Xian-Jie Yang, and their respective laboratories for discussions and collaborative research. We are supported by grants from the NIH and NNRI. DSW is a Jules and Doris Stein RPB Professor.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Departments of Ophthalmology and NeurobiologyUCLA School of MedicineLos AngelesUSA

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