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Design of Poly‐ l ‐Glutamate‐Based Complexes for pDNA Delivery
Author(s) -
NiñoPariente Amaya,
Armiñán Ana,
Reinhard Sören,
Scholz Claudia,
Wagner Ernst,
Vicent María J.
Publication year - 2017
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201700029
Subject(s) - chemistry , cationic polymerization , oligonucleotide , gene delivery , glutamic acid , endosome , dna , polyelectrolyte , biophysics , combinatorial chemistry , biochemistry , polymer chemistry , amino acid , polymer , genetic enhancement , gene , receptor , organic chemistry , biology
Abstract Due to the polyanionic nature of DNA, typically cationic or neutral delivery vehicles have been used for gene delivery. As a new approach, this study focuses on the design, development, and validation of nonviral polypeptide‐based carriers for oligonucleotide delivery based on a negatively charged poly‐ l ‐glutamic acid (PGA) backbone partly derivatized with oligoaminoamide residues. To this end, PGA‐derivatives modified with different pentameric succinyl tetraethylene pentamines (Stp 5 ) are designed. Optionally, histidines for modulation of endosomal buffer capacity and cysteines for pDNA complex stabilization are included, followed by characterization of biophysical properties and gene transfer efficiency in N2a neuroblastoma or 4T1 breast cancer cells.