Characterizing the encapsulation and release of lentivectors and adeno-associated vectors from degradable alginate hydrogels

Abstract

Gene therapy using viral vectors has been licensed for clinical use both in the European Union and the United States. Lentivectors (LV) and adeno-associated vectors (AAV) are two promising and FDA approved gene-therapy viral vectors. Many future applications of these vectors will benefit from targeting specific regions of interest within the body. Therefore, building on the early success of these vectors may depend on finding effective delivery systems to localize therapeutic administration. Degradable alginate hydrogels have been tested as appealing delivery vehicles for the controlled delivery of vector payloads. In this study, we compare the ability of two different degradable alginate hydrogel formulations to efficiently deliver LV and AAV. We propose that release rates of viral vectors are dependent on the physical properties of both the hydrogels and vectors. Here, we demonstrate that the initial strength and degradation rate of alginate hydrogels provides levers of control for tuning LV release but do not provide control in the release of AAV. While both alginate formulations used showed sustained release of both LV and AAV, LV release was shown to be dependent on alginate hydrogel degradation, while AAV release was largely governed by diffusive mechanisms. Altogether, this study demonstrates alginate's use as a possible delivery platform for LV and, for the first time, AAV – highlighting the potential of injectable degradable alginate hydrogels to be used as a versatile delivery tool in gene therapy applications.