Disulfide-linked polyethyleneglycol/peptide conjugates for the transfection of nucleic acids

A method of treating a subject comprising administering a polymeric carrier cargo complex formed of a nucleic acid and a polymeric carrier molecule according to formula (I):

• L-P1—S—[S—P2—S]n—S—P3-L
• wherein,
• P1 and P3 are different or identical to each other and represent a linear or branched hydrophilic polymer chain independently selected from the group consisting of polyethylene glycol (PEG), poly-N-(2-hydroxypropyl)methacrylamide, poly-2- (methacryloyloxy)ethyl phosphorylcholines, poly(hydroxyalkyl L-asparagine), poly(2-(methacryloyloxy)ethyl phosphorylcholine), hydroxyethylstarch and poly(hydroxyalkyl L-glutamine), wherein the hydrophilic polymer chain exhibits a molecular weight of 1 kDa to 100 kDa,
• P2 is a cationic or polycationic polypeptide having a length of 3 to 100 amino acids, and comprising at least two cysteine residues;
• —S—S— is a reversible disulfide bond, wherein one of the sulfur positions of each of the disulfide bonds in provided by the at least two cysteine residues of P2;
• L is a ligand, which may be present or not, independently selected from the group consisting of RGD, Transferrin, Folate, a signal peptide or signal sequence, a localization signal or sequence, a nuclear localization signal or sequence (NLS), an antibody, a cell penetrating peptide, TAT, a ligand of a receptor, a cytokine, a hormone, a growth factor, a small molecule, a carbohydrate, mannose, galactose, a synthetic ligand, a small molecule agonist, an inhibitor or antagonist of a receptor, and a RGD peptidomimetic analogue;
• and
• n is an integer selected from a range of 1 to 50.