3 years ago

Design of Poly-l-Glutamate-Based Complexes for pDNA Delivery

Design of Poly-l-Glutamate-Based Complexes for pDNA Delivery
María J. Vicent, Amaya Niño-Pariente, Ana Armiñán, Claudia Scholz, Ernst Wagner, Sören Reinhard
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 (Stp5) 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. A family of polyglutamate-succinyl tetraethylene pentamine (Stp) conjugates has been designed as efficient nonviral vectors for pDNA delivery. These polyplexes are successfully used for transfection of N2a cells, as proven by luciferase and green fluorescent protein-induced expression assays with absence of cytotoxicity at any relevant tested concentration. Additional Cys and His residues demonstrate the capability to tune polyplex transfection efficiency.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/mabi.201700029

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