biostudies-literatureKolster MXunta de GaliciaHorizon 2020 Framework ProgrammeEuropean Regional Development Fund36095-36105https://www.ebi.ac.uk/biostudies/studies/S-EPMC11261559biostudies-literatureUnknown16(28)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 <i>Saponaria officinalis</i> L., has been described as additive agent to enhance transfection efficiency (sapofection). However, the challenge to synchronize the saponin and gene delivery system <i>in vivo</i> 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 wereACS applied materials & interfacesBroadening the Scope of Sapofection: Cationic Peptide-Saponin Conjugates Improve Gene Delivery <i>In Vitro</i> and <i>In Vivo</i>.PMC11261559825730ED431G 2023/03ED431C 2022/21Weng ACorrea JFernandez-Megia EWeise CFuchs HSonntag AWalther WKolster MfalseBroadening the Scope of Sapofection: Cationic Peptide-Saponin Conjugates Improve Gene Delivery <i>In Vitro</i> and <i>In Vivo</i>.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 <i>Saponaria officinalis</i> L., has been described as additive agent to enhance transfection efficiency (sapofection). However, the challenge to synchronize the saponin and gene delivery system <i>in vivo</i> 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 were2024-01-01T00:00:00Z2024 Jul2026-06-01T20:38:28.825Z2025-06-01T01:16:03.907ZS-EPMC112615593897047010.1021/acsami.4c05846