Storage and Stability of AAV-Containing Fibrin Hydrogels for Retinal Gene Therapy

Berger, Aubrey; Knudsen, Travis; Kopp, Francesca; Korda, David; Lang, Mary; Scruggs, Brittni A.; Marmorstein, Alan D.

doi:10.3390/gels12070591

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Open AccessArticle

Storage and Stability of AAV-Containing Fibrin Hydrogels for Retinal Gene Therapy

by

Aubrey Berger

^1,2

,

Travis Knudsen

²,

Francesca Kopp

²,

David Korda

²

,

Mary Lang

^2,3

,

Brittni A. Scruggs

^2,4 and

Alan D. Marmorstein

^2,*

¹

Biomedical Graduate Program, Mayo Clinic, Rochester, MN 55905, USA

²

Department of Ophthalmology, Mayo Clinic, Rochester, MN 55905, USA

³

Mayo Clinic Alix School of Medicine, Mayo Clinic, Jacksonville, FL 32224, USA

⁴

Department of Pediatrics, Mayo Clinic, Rochester, MN 55905, USA

^*

Author to whom correspondence should be addressed.

Gels 2026, 12(7), 591; https://doi.org/10.3390/gels12070591

Submission received: 4 May 2026 / Revised: 22 June 2026 / Accepted: 25 June 2026 / Published: 2 July 2026

(This article belongs to the Special Issue Hydrogels for Encapsulation Applications)

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Abstract

Subretinal and intravitreal injection of retinal gene therapy is associated with serious adverse events and poor efficacy. We sought to improve retinal gene therapy delivery by developing fibrin hydrogel encapsulated adeno-associated virus (FE-AAV). Here we investigate conditions for storage and stability for FE-AAV. FE-AAV containing 1.9 × 10⁹ genome copies of AAV2/2-CMV-GFP was manufactured using fibrinogen reconstituted in 0.01 M sodium citrate, pH 7 (NaC) or phosphate-buffered saline containing 0.001% (v/v) Pluronic F68 (F68). Samples were stored at either −80 °C or 4 °C for up to 16 weeks. Changes in transduction efficiency, and mechanical and physical properties were evaluated. In vitro transduction was significantly (p < 0.05) reduced for FE-AAV manufactured with NaC. In contrast, we observed no change in transduction through 16 weeks for FE-AAV made with F68. Physical changes occurred in FE-AAV stored at −80 °C. In contrast to FE-AAV formulated with NaC, FE-AAV formulated with F68 and stored at 4 °C for 16 weeks was essentially equivalent to freshly made FE-AAV and retained the ability to transduce retinal pigment epithelial (RPE) cells in the pig eye. We conclude that FE-AAV formulated with F68 and stored at 4 °C is stable and shows potential for retinal gene therapy for at least 4 months following manufacture.

Keywords: gene therapy; hydrogel; AAV; retinal disease; storage; stability

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MDPI and ACS Style

Berger, A.; Knudsen, T.; Kopp, F.; Korda, D.; Lang, M.; Scruggs, B.A.; Marmorstein, A.D. Storage and Stability of AAV-Containing Fibrin Hydrogels for Retinal Gene Therapy. Gels 2026, 12, 591. https://doi.org/10.3390/gels12070591

AMA Style

Berger A, Knudsen T, Kopp F, Korda D, Lang M, Scruggs BA, Marmorstein AD. Storage and Stability of AAV-Containing Fibrin Hydrogels for Retinal Gene Therapy. Gels. 2026; 12(7):591. https://doi.org/10.3390/gels12070591

Chicago/Turabian Style

Berger, Aubrey, Travis Knudsen, Francesca Kopp, David Korda, Mary Lang, Brittni A. Scruggs, and Alan D. Marmorstein. 2026. "Storage and Stability of AAV-Containing Fibrin Hydrogels for Retinal Gene Therapy" Gels 12, no. 7: 591. https://doi.org/10.3390/gels12070591

APA Style

Berger, A., Knudsen, T., Kopp, F., Korda, D., Lang, M., Scruggs, B. A., & Marmorstein, A. D. (2026). Storage and Stability of AAV-Containing Fibrin Hydrogels for Retinal Gene Therapy. Gels, 12(7), 591. https://doi.org/10.3390/gels12070591

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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Storage and Stability of AAV-Containing Fibrin Hydrogels for Retinal Gene Therapy

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