Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Limited time window for retinal gene therapy in a preclinical model of ciliopathy

Poppy Datta, Avri Ruffcorn, Seongjin Seo
doi: https://doi.org/10.1101/2020.05.05.072793
Poppy Datta
1Department of Ophthalmology and Visual Sciences, The University of Iowa Carver College of Medicine, Iowa City, IA 52242
2Institute for Vision Research, The University of Iowa, Iowa City, IA 52242
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Avri Ruffcorn
1Department of Ophthalmology and Visual Sciences, The University of Iowa Carver College of Medicine, Iowa City, IA 52242
2Institute for Vision Research, The University of Iowa, Iowa City, IA 52242
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Seongjin Seo
1Department of Ophthalmology and Visual Sciences, The University of Iowa Carver College of Medicine, Iowa City, IA 52242
2Institute for Vision Research, The University of Iowa, Iowa City, IA 52242
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: seongjin-seo@uiowa.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

ABSTRACT

Retinal degeneration is a common clinical feature of ciliopathies, a group of genetic diseases linked to ciliary dysfunction, and gene therapy is an attractive treatment option to prevent vision loss. Although the efficacy of retinal gene therapy is well established by multiple proof-of-concept preclinical studies, its long-term effect, particularly when treatments are given at advanced disease stages, is controversial. Incomplete treatment and intrinsic variability of gene delivery methods may contribute to the variable outcomes. Here, we used a genetic rescue approach to “optimally” treat retinal degeneration at various disease stages and examined the long-term efficacy of gene therapy in a mouse model of ciliopathy. We used a Bardet-Biedl syndrome type 17 (BBS17) mouse model, in which the gene-trap that suppresses Bbs17 (also known as Lztfl1) expression can be removed by tamoxifen administration, restoring normal gene expression systemically. Our data indicate that therapeutic effects of retinal gene therapy decrease gradually as treatments are given at later stages. These results suggest the presence of limited time window for successful gene therapy in certain retinal degenerations. Our study also implies that the long-term efficacy of retinal gene therapy may depend on not only the timing of treatment but also other factors such as the function of mutated genes and residual activities of mutant alleles.

Competing Interest Statement

The authors have declared no competing interest.

  • Abbreviations

    AAV
    adeno-associated virus
    BBS
    Bardet-Biedl syndrome,
    CMV
    cytomegalovirus
    DAPI
    4′,6-Diamidine-2′-phenylindole dihydrochloride
    ERG
    electroretinography
    FLP
    flippase
    FRT
    flippase recognition target
    IFT
    intraflagellar transport
    IRD
    inherited retinal degeneration
    IS
    inner segment
    LCA
    Leber congenital amaurosis
    ONL
    outer nuclear layer
    OS
    outer segment
    P
    post-natal day
    PTI
    post-tamoxifen injection
    qRT-PCR
    quantitative reverse transcription polymerase chain reaction
    RP
    retinitis pigmentosa
    SCR
    standard combined response
    TEM
    transmission electron microscopy
    TMX
    tamoxifen
  • Copyright 
    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
    Back to top
    PreviousNext
    Posted May 06, 2020.
    Download PDF

    Supplementary Material

    Email

    Thank you for your interest in spreading the word about bioRxiv.

    NOTE: Your email address is requested solely to identify you as the sender of this article.

    Enter multiple addresses on separate lines or separate them with commas.
    Limited time window for retinal gene therapy in a preclinical model of ciliopathy
    (Your Name) has forwarded a page to you from bioRxiv
    (Your Name) thought you would like to see this page from the bioRxiv website.
    CAPTCHA
    This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
    Share
    Limited time window for retinal gene therapy in a preclinical model of ciliopathy
    Poppy Datta, Avri Ruffcorn, Seongjin Seo
    bioRxiv 2020.05.05.072793; doi: https://doi.org/10.1101/2020.05.05.072793
    Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
    Citation Tools
    Limited time window for retinal gene therapy in a preclinical model of ciliopathy
    Poppy Datta, Avri Ruffcorn, Seongjin Seo
    bioRxiv 2020.05.05.072793; doi: https://doi.org/10.1101/2020.05.05.072793

    Citation Manager Formats

    • BibTeX
    • Bookends
    • EasyBib
    • EndNote (tagged)
    • EndNote 8 (xml)
    • Medlars
    • Mendeley
    • Papers
    • RefWorks Tagged
    • Ref Manager
    • RIS
    • Zotero
    • Tweet Widget
    • Facebook Like
    • Google Plus One

    Subject Area

    • Neuroscience
    Subject Areas
    All Articles
    • Animal Behavior and Cognition (4685)
    • Biochemistry (10362)
    • Bioengineering (7682)
    • Bioinformatics (26343)
    • Biophysics (13534)
    • Cancer Biology (10694)
    • Cell Biology (15446)
    • Clinical Trials (138)
    • Developmental Biology (8501)
    • Ecology (12824)
    • Epidemiology (2067)
    • Evolutionary Biology (16867)
    • Genetics (11402)
    • Genomics (15484)
    • Immunology (10621)
    • Microbiology (25226)
    • Molecular Biology (10225)
    • Neuroscience (54482)
    • Paleontology (402)
    • Pathology (1669)
    • Pharmacology and Toxicology (2897)
    • Physiology (4345)
    • Plant Biology (9254)
    • Scientific Communication and Education (1587)
    • Synthetic Biology (2558)
    • Systems Biology (6781)
    • Zoology (1466)