Non-viral ocular gene therapy, pEYS606, for the treatment of non-infectious uveitis: Preclinical evaluation of the medicinal product

Journal of Controlled Release : Official Journal of the Controlled Release Society
Elodie TouchardF Behar-Cohen

Abstract

Non-infectious uveitis (NIU) is the first cause of blindness that can be cured if optimal anti-inflammatory therapy can be achieved. Systemic anti-TNF (Tumor Necrosis Factor) agents have been recently approved for NIU but no local delivery of anti-TNF is available. For sustained production of secreted therapeutic proteins into the eye, non-viral gene therapy using plasmid electrotransfer in the ciliary muscle has been proposed. In this paper, we report the development steps of pEYS606, a clinical-grade plasmid DNA, devoid of antiobiotic selection gene, encoding a fusion protein consisting of the extracellular domain of the soluble p55 TNF-α receptor linked to the human IgG1 Fc domain (hTNFR-Is/hIgG1 or Protein 6), with high affinity for human TNF-α, for non-viral gene transfer into the ocular ciliary muscle. Electrotransfer of pEYS606 in the ciliary muscle significantly reduced ocular inflammation in two well-established rat models of uveitis, the endotoxin-induced uveitis (EIU) and the experimental autoimmune uveitis (EAU). In addition, in EAU, a significant protection of photoreceptors was demonstrated after pEYS606 treatment. The improved pharmacokinetic profile of intraocularly-secreted protein as compared to direct intravi...Continue Reading

Citations

May 17, 2019·Expert Opinion on Drug Delivery·Francine Behar-Cohen
Apr 8, 2020·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Viral KansaraThomas A Ciulla
Sep 5, 2020·Pharmaceutics·Karine BigotFrancine Behar-Cohen
Oct 8, 2020·Médecine sciences : M/S·Florence HoogewoudFrancine Behar-Cohen
Feb 27, 2021·International Ophthalmology·Uwe PleyerChristoph Deuter
Mar 12, 2021·Pharmacology Research & Perspectives·María L FormicaSantiago D Palma
Aug 28, 2021·Biomolecules·Bhubanananda SahuHemant Khanna
Sep 30, 2021·International Ophthalmology Clinics·Ronald R Buggage, Thierry Bordet

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