Self-Assembled PEGylated Amphiphilic Polypeptides for Gene Transfection

60 Pages Posted: 18 May 2021

See all articles by Paul Klemm

Paul Klemm

Friedrich-Schiller-Universität Jena - Laboratory of Organic and Macromolecular Chemistry (IOMC)

Mira Behnke

Friedrich-Schiller-Universität Jena - Laboratory of Organic and Macromolecular Chemistry (IOMC)

Jana I. Solomun

Friedrich-Schiller-Universität Jena - Laboratory of Organic and Macromolecular Chemistry (IOMC)

Colin Bonduelle

University of Bordeaux

Sébastien Lecommandoux

University of Bordeaux

Anja Traeger

Friedrich-Schiller-Universität Jena - Laboratory of Organic and Macromolecular Chemistry (IOMC)

Stephanie Schubert

Friedrich-Schiller-Universität Jena - Jena Center for Soft Matter (JCSM)

Abstract

In the present study, three biodegradable block copolymers composed of a poly(ethylene glycole) block and a copolypeptide block with varying compositions of cationic L-lysine (L-Lys) and hydrophobic benzyl-L-glutamate (Bzl- L-Glu) were designed for gene delivery applications. The polypeptides were synthesized by ring opening polymerization (ROP) and after orthogonal deprotection of Boc-L-Lys side chains, the polymer exhibited an amphiphilic character. To bind or encapsulate plasmid DNA (pDNA), various formulations were investigated: Nanoprecipitation and emulsion technique using various organic solvents as well as an aqueous pH-controlled formulation method. The complex and nanoparticle (NP) formations were monitored by dynamic light scattering (DLS), and pDNA interaction was shown by gel electrophoresis and subsequent controlled release with heparin. The polypeptides were further tested for their cytotoxicity as well as biodegradability. The complexes and NPs presenting the most promising size distributions and DNA binding ability were subsequently evaluated for their transfection efficiency in HEK293T cells. The highest transfection efficiencies were obtained with an aqueous formulation of the polypeptide containing the highest L-Lys content and lowest proportion of hydrophobic, helical structures (P1* ), which is therefore a promising candidate for efficient gene delivery by biodegradable gene delivery vectors.

Suggested Citation

Klemm, Paul and Behnke, Mira and Solomun, Jana I. and Bonduelle, Colin and Lecommandoux, Sébastien and Traeger, Anja and Schubert, Stephanie, Self-Assembled PEGylated Amphiphilic Polypeptides for Gene Transfection. Available at SSRN: https://ssrn.com/abstract=3849029 or http://dx.doi.org/10.2139/ssrn.3849029

Paul Klemm

Friedrich-Schiller-Universität Jena - Laboratory of Organic and Macromolecular Chemistry (IOMC) ( email )

Germany

Mira Behnke

Friedrich-Schiller-Universität Jena - Laboratory of Organic and Macromolecular Chemistry (IOMC) ( email )

Germany

Jana I. Solomun

Friedrich-Schiller-Universität Jena - Laboratory of Organic and Macromolecular Chemistry (IOMC) ( email )

Germany

Colin Bonduelle

University of Bordeaux ( email )

Avenue Léon Duguit
Bordeaux, 33000
France

Sébastien Lecommandoux

University of Bordeaux ( email )

Avenue Léon Duguit
Bordeaux, 33000
France

Anja Traeger

Friedrich-Schiller-Universität Jena - Laboratory of Organic and Macromolecular Chemistry (IOMC) ( email )

Germany

Stephanie Schubert (Contact Author)

Friedrich-Schiller-Universität Jena - Jena Center for Soft Matter (JCSM) ( email )

Jena
Germany

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