DISULFIDE-LINKED POLYETHYLENEGLYCOL/PEPTIDE CONJUGATES FOR THE TRANSFECTION OF NUCLEIC ACIDS
First Claim
1. Polymeric carrier molecule according to generic formula (I):
-
L-P1—
S—
[S—
P2—
S]n—
S—
P3-Lwherein,P1 and P3 represent a linear or branched hydrophilic polymer chain, each P1 and P3 exhibiting at least one —
SH-moiety, capable to form a disulfide linkage upon condensation with component P2, the linear or branched hydrophilic polymer chain selected independent from each other from polyethylene glycol (PEG), poly-N-(2-hydroxypropyl)methacrylamide, poly-2-(methacryloyloxy)ethyl phosphorylcholines, poly(hydroxyalkyl L-asparagine) or poly(hydroxyalkyl L-glutamine), wherein the hydrophilic polymer chain exhibits a molecular weight of about 1 kDa to about 100 kDa;
P2 is a cationic or polycationic peptide or protein, having a length of about 3 to 100 amino acids, oris a cationic or polycationic polymer, having a molecular weight of about 0.5 kDa to about 100 kDa,each P2 exhibiting at least two —
SH-moieties, capable to form a disulfide linkage upon condensation with component(s) P1 and/or P3;
—
S—
S—
is a (reversible) disulfide bond;
L is an optional ligand, selected independent from the other from 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, or TAT;
n is an integer, selected from a range of about 1 to 50.
3 Assignments
0 Petitions
Accused Products
Abstract
The present invention is directed to an inventive polymeric carrier molecule according to generic formula (I) and variations thereof, which allows for efficient transfection of nucleic acids into cells in vivo and in vitro, a polymeric carrier cargo complex formed by a nucleic acid and the inventive polymeric carrier molecule, but also methods of preparation of this inventive polymeric carrier molecule and of the inventive polymeric carrier complex. The present invention also provides methods of application and use of this inventive polymeric carrier and the inventive polymeric carrier cargo complex as a medicament, for the treatment of various diseases, and in the preparation of a pharmaceutical composition for the treatment such diseases.
223 Citations
18 Claims
-
1. Polymeric carrier molecule according to generic formula (I):
-
L-P1—
S—
[S—
P2—
S]n—
S—
P3-Lwherein, P1 and P3 represent a linear or branched hydrophilic polymer chain, each P1 and P3 exhibiting at least one —
SH-moiety, capable to form a disulfide linkage upon condensation with component P2, the linear or branched hydrophilic polymer chain selected independent from each other from polyethylene glycol (PEG), poly-N-(2-hydroxypropyl)methacrylamide, poly-2-(methacryloyloxy)ethyl phosphorylcholines, poly(hydroxyalkyl L-asparagine) or poly(hydroxyalkyl L-glutamine), wherein the hydrophilic polymer chain exhibits a molecular weight of about 1 kDa to about 100 kDa;P2 is a cationic or polycationic peptide or protein, having a length of about 3 to 100 amino acids, or is a cationic or polycationic polymer, having a molecular weight of about 0.5 kDa to about 100 kDa, each P2 exhibiting at least two —
SH-moieties, capable to form a disulfide linkage upon condensation with component(s) P1 and/or P3;—
S—
S—
is a (reversible) disulfide bond;L is an optional ligand, selected independent from the other from 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, or TAT; n is an integer, selected from a range of about 1 to 50. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18)
-
Specification