July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Suprachoroidally delivered non-viral DNA nanoparticles transfect chorioretinal cells in non-human primates and rabbits
Author Affiliations & Notes
  • Viral Kansara
    Clearside Biomedical, Inc, Georgia, United States
  • Jesse Yoo
    Clearside Biomedical, Inc, Georgia, United States
  • Mark J Cooper
    Copernicus Therapeutics, Inc, Ohio, United States
  • Ozge Sensenoglu Laird
    Copernicus Therapeutics, Inc, Ohio, United States
  • Donna Taraborelli
    Clearside Biomedical, Inc, Georgia, United States
  • Robert Moen
    Copernicus Therapeutics, Inc, Ohio, United States
  • Glenn Noronha
    Clearside Biomedical, Inc, Georgia, United States
  • Footnotes
    Commercial Relationships   Viral Kansara, Clearside Biomedical, Inc (I); Jesse Yoo, Clearside Biomedical, Inc (I); Mark Cooper, Copernicus Therapeutics, Inc (I); Ozge Laird, Copernicus Therapeutics, Inc (I); Donna Taraborelli, Clearside Biomedical, Inc (I); Robert Moen, Copernicus Therapeutics, Inc (I); Glenn Noronha, Clearside Biomedical, Inc (I)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2909. doi:
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      Viral Kansara, Jesse Yoo, Mark J Cooper, Ozge Sensenoglu Laird, Donna Taraborelli, Robert Moen, Glenn Noronha; Suprachoroidally delivered non-viral DNA nanoparticles transfect chorioretinal cells in non-human primates and rabbits. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2909.

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

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Abstract

Purpose : Suprachoroidal delivery offers the potential to more precisely target chorioretinal tissues while avoiding surgical risks associated with a subretinal injection and may offer a novel alternative for gene-based therapies for the treatment of ocular diseases. The purpose of this effort was to evaluate ocular tolerability and chorioretinal cell transfectability of suprachoroidally injected non-viral DNA nanoparticles (DNPs) in non-human primates (NHPs) and rabbits.

Methods : Two separate studies evaluated chorioretinal cell transfectability and ocular tolerability of suprachoroidally injected non-viral DNPs in NHPs and in rabbits. The DNPs consisted of a single copy of plasmid DNA with a polyubiquitin C/luciferase transcriptional cassette. Cynomolgus monkeys (N=4 per group) received a single bilateral suprachoroidal injection (0.1 mL) of either saline (negative control), ellipsoid-shaped DNPs, or rod-shaped DNPs. New Zealand White rabbits (N=4 per group) received a single suprachoroidal injection (0.1 mL) of either saline (negative control), ellipsoid-shaped DNPs, or rod-shaped DNPs. A cohort of rabbits also received a single unilateral (left eye) subretinal injection of rod-shaped DNPs. Animals were assessed for anterior segment inflammation, for intraocular pressure changes and for electroretinographic changes, at baseline, day 1, and day 7 post-dose in the rabbit study, and at baseline, day 1, day 8 and day 22 post-dose in the NHPs. Luciferase activity was measured in NHP ocular tissues by bioluminescence assay.

Results : Suprachoroidally injected non-viral DNPs were generally well-tolerated in NHPs and rabbits. Luciferase activity was observed in the retina and choroid of eyes that received suprachoroidal injections in NHPs and rabbits. In NHPs, the persistence of luciferase activity was observed through day 22 (last study timepoint) with ellipsoid-shaped DNPs, while a significant decline (95%) in choroid/RPE was observed with rod-shaped DNPs at day 22. In rabbits, suprachoroidally injected DNPs (both rod and ellipsoid) and subretinal DNPs (rod-shape) resulted in comparable luciferase activity at week 1 (last study timepoint).

Conclusions : Suprachoroidal administration of non-viral DNPs resulted in efficient chorioretinal transfection in NHPs and rabbits. Suprachoroidally injected DNPs were well tolerated and will be further evaluated for their safety and efficacy.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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