Apaolaza, P. S. and del Pozo-Rodriguez, A. and Torrecilla, J. and Rodriguez-Gascon, A. and Rodriguez, J. M. and Friedrich, U. and Weber, B. H. F. and Solinis, M. A. (2015) Solid lipid nanoparticle-based vectors intended for the treatment of X-linked juvenile retinoschisis by gene therapy: In vivo approaches in Rs1h-deficient mouse model. JOURNAL OF CONTROLLED RELEASE, 217. pp. 273-283. ISSN 0168-3659, 1873-4995
Full text not available from this repository. (Request a copy)Abstract
X-linked juvenile retinoschisis (XLRS), which results from mutations in the gene RS1 that encodes the protein retinoschisin, is a retinal degenerative disease affecting between 1/5000 and 1/25,000 people worldwide. Currently, there is no cure for this disease and the treatment is based on the application of low-vision aids. The aim of the present work was the in vitro and in vivo evaluation of two different non-viral vectors based on solid lipid nanoparticles (SLNs), protamine and two anionic polysaccharides, hyaluronic acid (HA) or dextran (DX), for the treatment of XLRS. First, the vectors containing a plasmid which encodes both the reporter green fluorescent protein (GFP) and the therapeutic protein retinoschisin, under the control of CMV promoters, were characterized in vitro. Then, the vectors were subretinally or intravitreally administrated to C57BL/6 wild type mice. One week later, GFP was detected in all treated mice and in all retinal layers except in the Outer Nuclear Layer (ONL) and the Inner Nuclear Layer (INL), regardless of the administration route and the vector employed. Finally, two weeks after subretinal or intravitreal injection to Rs1h-deficient mice, GFP and retinoschisin expression was detected in all retinal layers, except in the ONL, which was maintained for at least two months after subretinal administration. The structural analysis of the treated Rs1h-deficient eyes showed a partial recovery of the retina related to the production of retinoschisin. This work shows for the first time a successful RS1 gene transfer to Rs1h-deficient animals using non-viral nanocarriers, with promising results that point to non-viral gene therapy as a feasible future therapeutic tool for retinal disorders. (c) 2015 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HYALURONIC-ACID; CELL TRANSFECTION; RNA INTERFERENCE; NONVIRAL VECTOR; DEFICIENT MOUSE; DELIVERY; RETINA; VITRO; NANOCARRIERS; PROTAMINE; Solid lipid nanoparticles; X-linked juvenile retinoschisis; Non-viral vector; Hyaluronic acid; Dextran; Gene therapy |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 May 2019 09:51 |
| Last Modified: | 07 May 2019 09:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4465 |
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