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Article

Controlled Release of rAAV Vectors from APMA-Functionalized Contact Lenses for Corneal Gene Therapy

1
Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, I+DFarma, Facultad de Farmacia and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
2
Cell Therapy and Regenerative Medicine Unit, Centro de Investigacións Científicas Avanzadas (CICA), Universidade da Coruña, Campus de A Coruña, 15071 A Coruña, Spain
3
Center of Experimental Orthopaedics, Saarland University Medical Center, 66421 Homburg, Germany
*
Author to whom correspondence should be addressed.
Equal contribution. Shared first authorship.
Pharmaceutics 2020, 12(4), 335; https://doi.org/10.3390/pharmaceutics12040335
Received: 17 March 2020 / Revised: 3 April 2020 / Accepted: 7 April 2020 / Published: 9 April 2020
(This article belongs to the Special Issue Scaffold-Mediated Gene Delivery)
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. View Full-Text
Keywords: therapeutic contact lens; gene therapy; rAAV vectors; controlled release; corneal diseases therapeutic contact lens; gene therapy; rAAV vectors; controlled release; corneal diseases
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MDPI and ACS Style

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

AMA Style

Alvarez-Rivera F, Rey-Rico A, Venkatesan JK, 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(4):335. https://doi.org/10.3390/pharmaceutics12040335

Chicago/Turabian Style

Alvarez-Rivera, Fernando, Ana Rey-Rico, Jagadeesh K. Venkatesan, Luis Diaz-Gomez, Magali Cucchiarini, Angel Concheiro, and Carmen Alvarez-Lorenzo. 2020. "Controlled Release of rAAV Vectors from APMA-Functionalized Contact Lenses for Corneal Gene Therapy" Pharmaceutics 12, no. 4: 335. https://doi.org/10.3390/pharmaceutics12040335

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