RT Journal Article
T1 Broadening the Scope of Sapofection: Cationic Peptide-Saponin Conjugates Improve Gene Delivery In Vitro and In Vivo
A1 Kolster, Meike
A1 Sonntag, Alexander
A1 Weise, Christoph
A1 Correa Chinea, Juan Francisco
A1 Fuchs, Hendrick
A1 Walther, Wolfgang
A1 Fernández Megía, Eduardo
A1 Weng, Alexander
K1 Gene therapy
K1 Endosomal escape
K1 Saponin
K1 Polylysine
K1 SO1861
AB Gene therapies represent promising new therapeutic options for a variety of indications. However, despite several approved drugs, its potential remains untapped. For polymeric gene delivery, endosomal escape represents a bottleneck. SO1861, a naturally occurring triterpene saponin with endosomal escape properties isolated from Saponaria officinalis L., has been described as additive agent to enhance transfection efficiency (sapofection). However, the challenge to synchronize the saponin and gene delivery system in vivo imposes limitations. Herein, we address this issue by conjugating SO1861 to a peptide-based gene vector using a pH-sensitive hydrazone linker programmed to release SO1861 at the acidic pH of the endosome. Nanoplexes formulated with SO1861-equipped peptides were investigated for transfection efficiency and tolerability in vitro and in vivo. In all investigated cell lines, SO1861-conjugated nanoplexes have shown superior transfection efficiency and cell viability over supplementation of transfection medium with free SO1861. Targeted SO1861-equipped nanoplexes incorporating a targeting peptide were tested in vitro and in vivo in an aggressively growing neuroblastoma allograft model in mice. Using a suicide gene vector encoding the cytotoxic protein saporin, a slowed tumor growth and improved survival rate were observed for targeted SO1861-equipped nanoplexes compared to vehicle control
PB ACS
SN 1944-8244
YR 2024
FD 2024-07-06
LK http://hdl.handle.net/10347/34842
UL http://hdl.handle.net/10347/34842
LA eng
NO ACS Appl. Mater. Interfaces 2024, 16, 28, 36095–36105
NO This work has received funding from the European Union Horizon 2020 research and innovation programme under grant agreement No 825730. We thank Sapreme Technologies for generously providing SO1861-EMCH. E.F.-M. also thanks financial support from Xunta de Galicia (ED431C 2022/21, and Centro de Investigación do Sistema Universitario de Galicia accreditation 2023-2027, ED431G 2023/03) and the European Union (European Regional Development Fund - ERDF)
DS Minerva
RD 23 abr 2026