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Controlled Release of rAAV Vectors from APMA-Functionalized Contact Lenses for Corneal Gene Therapy
dc.contributor.author | Álvarez-Rivera, Fernando | |
dc.contributor.author | Rey-Rico, Ana | |
dc.contributor.author | Venkatesan, Jagadeesh K. | |
dc.contributor.author | Díaz-Gómez, Luis | |
dc.contributor.author | Cucchiarini, Magali | |
dc.contributor.author | Concheiro, Ángel | |
dc.contributor.author | Álvarez-Lorenzo, Carmen | |
dc.date.accessioned | 2020-05-07T09:59:38Z | |
dc.date.available | 2020-05-07T09:59:38Z | |
dc.date.issued | 2020-04-09 | |
dc.identifier.citation | Alvarez-Rivera, F.; Rey-Rico, A.; Venkatesan, J.K.; Diaz-Gomez, L.; Cucchiarini, M.; Concheiro, A.; Alvarez-Lorenzo, C. Controlled Release of rAAV Vectors from APMA-Functionalized Contact Lenses for Corneal Gene Therapy. Pharmaceutics 2020, 12, 335. https://doi.org/10.3390/pharmaceutics12040335 | es_ES |
dc.identifier.issn | 1999-4923 | |
dc.identifier.uri | http://hdl.handle.net/2183/25512 | |
dc.description.abstract | [Abstract] As an alternative to eye drops and ocular injections for gene therapy, the aim of this work was to design for the first time hydrogel contact lenses that can act as platforms for the controlled delivery of viral vectors (recombinant adeno-associated virus, rAAV) to the eye in an effective way with improved patient compliance. Hydrogels of hydroxyethyl methacrylate (HEMA) with aminopropyl methacrylamide (APMA) (H1: 40, and H2: 80 mM) or without (Hc: 0 mM) were synthesized, sterilized by steam heat (121 ◦C, 20 min), and then tested for gene therapy using rAAV vectors to deliver the genes to the cornea. The hydrogels showed adequate light transparency, oxygen permeability, and swelling for use as contact lenses. Loading of viral vectors (rAAV-lacZ, rAAV-RFP, or rAAV-hIGF-I) was carried out at 4 ◦C to maintain viral vector titer. Release in culture medium was monitored by fluorescence with Cy3-rAAV-lacZ and AAV Titration ELISA. Transduction efficacy was tested through reporter genes lacZ and RFP in human bone marrow derived mesenchymal stem cells (hMSCs). lacZ was detected with X-Gal staining and quantified with Beta-Glo®, and RFP was monitored by fluorescence. The ability of rAAV-hIGF-I-loaded hydrogels to trigger cell proliferation in hMSCs was evaluated by immunohistochemistry. Finally, the ability of rAAV-lacZ-loaded hydrogels to transduce bovine cornea was confirmed through detection with X-Gal staining of β-galactosidase expressed within the tissue. | es_ES |
dc.description.sponsorship | This research was funded by MINECO (SAF2017-83118-R), Agencia Estatal de Investigación (AEI) Spain, Xunta de Galicia (ED431C 2016/008) and FEDER. A.R.R thanks the InTalent program from UDC-Inditex for the research grant. | es_ES |
dc.description.sponsorship | Xunta de Galicia; ED431C 2016/008 | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.relation | info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/SAF2017-83118-R/ES/ARQUITECTURAS POLIMERICAS 3D ACTIVAS PARA MEDICINA REGENERATIVA Y TERAPIA LOCALIZADA | |
dc.relation.uri | https://doi.org/10.3390/pharmaceutics12040335 | es_ES |
dc.rights | Atribución 4.0 Internacional (CC BY 4.0) | es_ES |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Therapeutic contact lens | es_ES |
dc.subject | Gene therapy | es_ES |
dc.subject | rAAV vectors | es_ES |
dc.subject | Controlled release | es_ES |
dc.subject | Corneal diseases | es_ES |
dc.title | Controlled Release of rAAV Vectors from APMA-Functionalized Contact Lenses for Corneal Gene Therapy | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.access | info:eu-repo/semantics/openAccess | es_ES |
UDC.journalTitle | Pharmaceutics | es_ES |
UDC.volume | 12 | es_ES |
UDC.issue | 4 | es_ES |
UDC.startPage | 335 | es_ES |
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