July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Evolution of recombinant adeno-associated viral vectors with favourable retinal penetration properties
Author Affiliations & Notes
  • Sonja Kleinlogel
    Institute of Physiology, University of Bern, Bern, Switzerland
  • Elmar Hulliger
    Institute of Physiology, University of Bern, Bern, Switzerland
  • Michiel van Wyk
    Institute of Physiology, University of Bern, Bern, Switzerland
  • Anand David
    Institute of Physiology, University of Bern, Bern, Switzerland
  • Margarete Odenthal
    Institute of Pathology, University Hospital Cologne, Cologne, Germany
  • Hildegard Büning
    Institute of Experimental Hematology, Medizinische Hochschule Hannover (MHH), Hannover, Germany
  • Footnotes
    Commercial Relationships   Sonja Kleinlogel, Haag-Streit Medtech AG (F); Elmar Hulliger, None; Michiel van Wyk, Haag-Streit Medtech AG (F); Anand David, None; Margarete Odenthal, None; Hildegard Büning, None
  • Footnotes
    Support  Grant from the Swiss National Science Foundation (SNF) 31003A_176065
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1194. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Sonja Kleinlogel, Elmar Hulliger, Michiel van Wyk, Anand David, Margarete Odenthal, Hildegard Büning; Evolution of recombinant adeno-associated viral vectors with favourable retinal penetration properties. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1194.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Most retinal degenerative diseases, including retinitis pigmentosa and age-related macular degeneration, are characterized by a progressive loss of photoreceptors. Various adeno-associated virus (AAV)-based gene therapies to prevent or slow down retinal degeneration target the photoreceptor cells. Typically, AAVs are injected subretinally. This restricts therapeutic intervention to the injection site and often results in a decrease in retinal thickness and visual acuity. Intravitreal injection is a safer method and targets cells along the entire width of the retina. Therefore, AAV vectors are developed that possess the ability to penetrate through the retina when applied intravitreally.

Methods : To develop AAV2 vectors with good retinal penetration abilities following intravitreal delivery, we applied an in vivo directed evolution strategy using a novel peptide display design that enabled us to iteratively enrich AAV2 variants with the desired properties. After four selection rounds we determined and ranked the receptor-binding motifs of the converged library by next-generation sequencing.

Results : Fifteen synthetic capsids containing the top-ranked motifs were subsequently analysed for their transduction fingerprints following intravitreal injection into wildtype C57/BL6 mouse eyes. For evaluation, a transgene encoding the green fluorescent protein mCitrine under the ubiquitous CMV and EF1a promoters was packaged into the novel capsids. The in vivo expression screen resulted in three synthetic AAV capsids with much improved transretinal penetration abilities compared to wildtype AAV2, mediating panretinal mCitrine expression.

Conclusions : Our novel synthetic AAV2 capsids may have clinical relevance for the implementation of photoreceptor-targeted gene therapies, but also optogenetic approaches targeting dormant photoreceptors or inner retinal cells.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×