Adeno-associated virus vector hydrogel formulations for brain cancer gene therapy applications.

Autor: Słyk Ż; Department of Applied Pharmacy, Faculty of Pharmacy, Medical University of Warsaw, Warsaw, Poland; Laboratory of Gene Therapy, Faculty of Pharmacy, Medical University of Warsaw, Warsaw, Poland. Electronic address: zaneta.slyk@wum.edu.pl., Wrzesień R; Central Laboratory of Experimental Animals, Center for Preclinical Research and Technology, Medical University of Warsaw, Warsaw, Poland., Barszcz S; Department of Neurosurgery, Children's Clinical Hospital, University Clinical Centre of the Medical University of Warsaw, Warsaw, Poland., Gawrychowski K; Department of Applied Pharmacy, Faculty of Pharmacy, Medical University of Warsaw, Warsaw, Poland., Małecki M; Department of Applied Pharmacy, Faculty of Pharmacy, Medical University of Warsaw, Warsaw, Poland; Laboratory of Gene Therapy, Faculty of Pharmacy, Medical University of Warsaw, Warsaw, Poland.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Jan; Vol. 170, pp. 116061. Date of Electronic Publication: 2023 Dec 27.
DOI: 10.1016/j.biopha.2023.116061
Abstrakt: Gelatin-based formulations are utilized in neurosurgical procedures, with Medisponge® serving as an illustration of a secure and biocompatible hemostatic formulation. Noteworthy are combined hemostatic products that integrate pharmacological agents with gelatin. Gelatin matrices, which host biologically active substances, provide a platform for a variety of molecules. Biopolymers function as carriers for chemicals and genes, a facet particularly pertinent in brain cancer therapy, as gene therapy complement conventional approaches. The registration of Zolgensma underscores the efficacy of rAAV vectors in therapeutic gene delivery to the CNS. rAAVs, renowned for their safety, stability, and neuron-targeting capabilities, predominate in CNS gene therapy studies. The effectiveness of rAAV vector therapy varies based on the serotype and administration route. Local gene therapy employing hydrogel (e.g., post-tumor resection) enables the circumvention of the blood-brain barrier and restricts formulation diffusion. This study formulates gelatin rAAV gene formulations and evaluates vector transduction potential. Transduction efficiency was assessed using ex vivo mouse brains and in vitro cancer cell lines. In vitro, the transduction of rAAV vectors in gelatin matrices was quantified through qPCR, measuring the itr and Gfp expression. rAAVDJ and rAAV2 demonstrated superior transduction in ex vivo and in vitro models. Among the cell lines tested (Hs683, B16-F10, NIH:OVCAR-3), gelatin matrix F1 exhibited selective transduction, particularly with Hs683 human glioma cells, surpassing the performance Medisponge®. This research highlights the exploration of local brain cancer therapy, emphasizing the potential of gelatin as an rAAV vector carrier for gene therapy. The functional transduction activity of gelatin rAAV formulations is demonstrated.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier Masson SAS.)
Databáze: MEDLINE
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