Compositions of polyplexes and saponins

The saponin-equipped polyplex according to any one of the preceding claims, wherein the amount of the saponin molecule equivalents per amount of molecules of the polymeric scaffold in the polyplexing agent is comprised between 0.05 and 4, preferably between 0.1 and 2, more preferably between 0.15 and 1, even more preferably between 0.2 and 0.75, and most preferably is either equal to or about 0.5.

The saponin-equipped polyplex according to any one of the preceding claims, wherein the polymeric scaffold is or comprises polyamidoamine dendrimer, further referred to as PAMAM, preferably wherein the PAMAM comprises ethylenediamine core and/or wherein the PAMAM is at least generation 3 PAMAM or higher, preferably is generation 5 PAMAM.

The saponin-equipped polyplex according to any one of the preceding claims, wherein the saponin comprises an aglycone core structure selected from quillaic acid or gypsogenin, preferably wherein the aglycone core structure is quillaic acid.

The saponin-equipped polyplex according to any one of the preceding claims, wherein the saponin is at least a monodesmosidic saponin comprising at least a first saccharide chain comprising at least three sugar residues in a branched configuration, or is at least a bidesmosidic saponin further comprising a second saccharide chain comprising a glucuronic acid residue, preferably being a terminal glucuronic acid residue;

• preferably wherein the first branched saccharide chain comprises a terminal fucose residue and/or a terminal rhamnose residue and preferably comprises at least four sugar residues, and/or wherein the second saccharide chain is Gal-(1→2)-[Xyl-(1→3)]-GlcA;
• more preferably wherein the saponin comprises the first saccharide chain at position C-28 of the saponin's aglycone core structure, and/or the second saccharide chain at position C-3 of the saponin's aglycone core structure;
• most preferably wherein the first saccharide chain is a carbohydrate substituent at the C-28-OH group of the saponin's aglycone core structure and/or wherein the second saccharide chain is a carbohydrate substituent at the C-3beta-OH group of the saponin's aglycone core structure.

The saponin-equipped polyplex according to any one of the preceding claims, wherein the saponin is any one or more of AG1856, GE1741, a saponin isolated from Quillaja saponaria, Quil-A, QS-17, QS-21, QS-7, SA1641, a saponin isolated from Saponaria officinalis, SO1542, SO1584, SO1658, SO1674, SO1700, SO1730, SO1772, Saponarioside B, SO1832, SO1861, SO1862 and SO1904;

• preferably wherein the saponin is any one or more of QS-21, SO1832, SO1861, SA1641 and GE1741;
• more preferably wherein the saponin is QS-21, SO1832 or SO1861;
• most preferably being SO1861.

The saponin-equipped polyplex according to any one of the preceding claims, wherein the saponin is a saponin isolated from Saponaria officinalis, preferably wherein the saponin is any one or more of SO1542, SO1584, SO1658, SO1674, SO1700, SO1730, SO1772, Saponarioside B, SO1832, SO1861, SO1862 and SO1904;

• more preferably wherein the saponin is any one or more of SO1832, SO1861 and SO1862;
• even more preferably wherein the saponin is SO1832 and SO1861;
• most preferably being SO1861.

The saponin-equipped polyplex according to any one of the preceding claims, wherein the nucleic acid is selected from a plasmid, a minicircle DNA, cDNA, mRNA, siRNA, oligonucleotide, and any modified equivalent thereof comprising one or more nucleotide analogues, preferably wherein the nucleic acid is a plasmid, more preferably wherein the nucleic acid comprises at least 0.25 kbp, more preferably at least 1 kbp, even more preferably at least 2.5 kbp, most preferably at least 5 kbp.

The saponin-equipped polyplex according to any one of the preceding claims, wherein the linker is an acid-sensitive linker that comprises a covalent bond selected from any one or more of a hydrazone bond, an imine bond, an ester bond, a dioxalane bond, and an oxime bond, preferably wherein the acid-sensitive linker comprises a hydrazone bond.

The saponin-equipped polyplex according to any one of the preceding claims, wherein the aldehyde group at position C-23 of the saponin's aglycone core structure has been engaged in forming the covalent bond with the linker.

Pharmaceutical composition comprising the saponin-equipped polyplex according to any one of the preceding claims, preferably further comprising a pharmaceutically acceptable excipient and/or pharmaceutically acceptable diluent.