Modified fibrin hydrogel for sustained delivery of RNAi lipopolyplexes in skeletal muscle.

Autor:	Ngarande E; Cardiovascular Research Unit, Department of Surgery, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa., Doubell E; Cardiovascular Research Unit, Department of Surgery, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa., Tamgue O; International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, Observatory 7925, South Africa.; Institute of Infectious Diseases and Molecular Medicine (IDM), Department of Pathology, Division of Immunology and South African Medical Research Council (SAMRC) Immunology of Infectious Diseases, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa., Mano M; King's College London, British Heart Foundation Centre of Research Excellence, School of Cardiovascular Medicine & Sciences, WC2R 2LS, London, UK., Human P; Cardiovascular Research Unit, Department of Surgery, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa., Giacca M; King's College London, British Heart Foundation Centre of Research Excellence, School of Cardiovascular Medicine & Sciences, WC2R 2LS, London, UK., Davies NH; Cardiovascular Research Unit, Department of Surgery, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa.
Jazyk:	angličtina
Zdroj:	Regenerative biomaterials [Regen Biomater] 2022 Dec 13; Vol. 10, pp. rbac101. Date of Electronic Publication: 2022 Dec 13 (Print Publication: 2023).
DOI:	10.1093/rb/rbac101
Abstrakt:	RNA interference is a promising therapeutical approach presently hindered by delivery concerns such as rapid RNA degradation and targeting of individual tissues. Injectable hydrogels are one potentially simple and direct route towards overcoming these barriers. Here we report on the utility of a combination of a mildly modified form of the clinically utilised fibrin hydrogel with Invivofectamine ® 3.0, a lipid nonviral transfection vector, for local and sustained release. PEGylation of fibrin allowed for controlled release of small interfering RNA (siRNA)-lipopolyplexes for at least 10 days and greatly increased the stability of fibrin in vitro and in vivo . A 3D cell culture model and a release study showed transfection efficacy of siRNA-lipopolyplexes was retained for a minimum of 7 days. Injection in conjunction with PEGylated-fibrinogen significantly increased retention of siRNA-lipopolyplexes in mouse skeletal muscle and enhanced knockdown of myostatin mRNA that correlated with muscle growth. Thus, the increased efficacy observed here for the combination of a lipid nanoparticle, the only type of nonviral vector approved for the clinic, with fibrin, might allow for more rapid translation of injectable hydrogel-based RNA interference. (© The Author(s) 2022. Published by Oxford University Press.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu