UMMS Affiliation

Department of Ophthalmology; Horae Gene Therapy Center

Publication Date


Document Type



Eye Diseases | Genetic Phenomena | Genetics and Genomics | Ophthalmology | Therapeutics


Mutations in the cilia-centrosomal protein CEP290 are frequently observed in autosomal recessive childhood blindness disorder Leber congenital amaurosis (LCA). No treatment or cure currently exists for this disorder. The Cep290(rd16) (retinal degeneration 16) mouse (a model of LCA) carries a mutation in the Cep290 gene. This mutation leads to shorter cilia formation and defective photoreceptor structure and function. A roadblock to developing a gene replacement strategy for CEP290 using conventional adeno-associated virus (AAV) vectors is its large size. The identification and characterization is reported of a miniCEP290 gene that is amenable to AAV2/8-mediated delivery and delaying retinal degeneration in the Cep290(rd16) mice. Using the ability of Cep290(rd16) mouse embryonic fibroblasts to from shorter cilia as a platform, a human CEP290 domain encoded by amino acids 580-1180 (miniCEP290(580-1180)) was identified that can recover the cilia length in vitro. Furthermore, subretinal injection of AAV particles carrying the cDNA expressing miniCEP290(580-1180) into neonatal Cep290(rd16) mice resulted in significantly improved photoreceptor survival, morphology, and function compared to control injected mice. These studies show the potential of using a truncated CEP290 to treat this fast progressing and devastating disease.


LCA, cilia, ciliopathies, gene therapy, photoreceptor, retina

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© Wei Zhang et al. 2018; Published by Mary Ann Liebert, Inc. This article is available under the Creative Commons License CC-BY-NC ( This license permits non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited. Permission only needs to be obtained for commercial use and can be done via RightsLink.

DOI of Published Version



Hum Gene Ther. 2018 Jan;29(1):42-50. doi: 10.1089/hum.2017.049. Epub 2017 Jul 5. Link to article on publisher's site

Journal/Book/Conference Title

Human gene therapy

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Link to Article in PubMed

PubMed ID


Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License