biostudies-literatureHe JNIBIB NIH HHSNational Institutes of HealthNIH HHSe3295https://www.ebi.ac.uk/biostudies/studies/S-EPMC7900953biostudies-literatureUnknown23(2)<h4>Background</h4>Previously, we determined that four-branched histidine-lysine (HK) peptides were effective carriers of plasmids and small interfering RNA. In the present study, we compared several branched HK carriers and, in particular, two closely-related H3K4b and H3K(+H)4b peptides for their ability as carriers of mRNA. The H3K(+H)4b peptide differed from its parent analogue, H3K4b, by only a single histidine in each branch.<h4>Methods</h4>A series of four-branched HK peptides with varied sequences was synthesized on a solid-phase peptide synthesizer. The ability of these peptides to carry mRNA expressing luciferase to MDA-MB-231 cells was investigated. With gel retardation and heparin displacement assays, the stability of HK polyplexes was examined. We determined the intracellular The journal of gene medicineLocation of a single histidine within peptide carriers increases mRNA delivery.PMC7900953R01‐EB028534R01-EB028534R01 EB028534Leng QHe JXu SMixson AJfalseLocation of a single histidine within peptide carriers increases mRNA delivery.<h4>Background</h4>Previously, we determined that four-branched histidine-lysine (HK) peptides were effective carriers of plasmids and small interfering RNA. In the present study, we compared several branched HK carriers and, in particular, two closely-related H3K4b and H3K(+H)4b peptides for their ability as carriers of mRNA. The H3K(+H)4b peptide differed from its parent analogue, H3K4b, by only a single histidine in each branch.<h4>Methods</h4>A series of four-branched HK peptides with varied sequences was synthesized on a solid-phase peptide synthesizer. The ability of these peptides to carry mRNA expressing luciferase to MDA-MB-231 cells was investigated. With gel retardation and heparin displacement assays, the stability of HK polyplexes was examined. We determined the intracellular 2021-01-01T00:00:00Z2021 Feb2025-05-29T22:28:04.437Z2025-05-29T22:28:04.437ZS-EPMC79009533317154010.1002/jgm.3295