Abstract
As a promising strategy for the treatment of various diseases, gene therapy has attracted increasing attention over the past decade. Among various gene delivery approaches, non-viral vectors made of synthetic biomaterials have shown significant potential. Due to their synthetic nature, non-viral vectors can have tunable structures and properties by using various building units. In particular, they can offer advantages over viral vectors with respect to biosafety and cytotoxicity. In this study, a well-defined poly(ethylene glycol)-block-poly(α-(propylthio-N,N-diethylethanamine hydrochloride)-ε-caprolactone) diblock polymer (PEG-b-CPCL) with one poly(ethylene glycol) (PEG) block and one tertiary amine-functionalized cationic poly(ε-caprolactone) (CPCL) block, as a novel non-viral vector in the delivery of plasmid DNA (pDNA), was synthesized and studied. Despite having a degradable polymeric structure, the polymer showed remarkable hydrolytic stability over multiple weeks. The optimal ratio of the polymer to pDNA for nanocomplex formation, pDNA release from the nanocomplex with the presence of heparin, and serum stability of the nanocomplex were probed through gel electrophoresis. Nanostructure of the nanocomplexes was characterized by DLS and TEM imaging. Relative to CPCL homopolymers, PEG-b-CPCL led to better solubility over a wide range of pH. Overall, this work demonstrates that PEG-b-CPCL possesses a range of valuable properties as a promising synthetic vector for pDNA delivery.
Highlights
The first clinical study on gene therapy was conducted at the National Institutes of Health (NIH)in 1989, and it demonstrated that genetically modified human cells could be transferred to patients in a feasible and safe manner [1]
We report upon poly(ethylene glycol)-block-poly(α-(propylthio-N,N-diethylethana mine hydrochloride)-ε-caprolactone) diblock polymer (PEG-b-cationic poly(ε-caprolactone) (CPCL)) with one poly(ethylene glycol)
We investigated the delivery of genetic material, such as plasmid DNA (pDNA) and small interfering ribonucleic acid (siRNA), using cationic polylactides (CPLAs) [25,26,27]
Summary
The first clinical study on gene therapy was conducted at the National Institutes of Health (NIH)in 1989, and it demonstrated that genetically modified human cells could be transferred to patients in a feasible and safe manner [1]. The first clinical study on gene therapy was conducted at the National Institutes of Health (NIH). Almost 2600 clinical trials on gene therapy have been initiated or performed worldwide through November 2017 [2]. Six gene delivery products have been approved by the U.S Food and Drug Administration (FDA), European Marketing. Authorization (EMA), and the China Food and Drug Administration (CFDA), indicating steady development and growing confidence in gene therapy [2]. Various approaches for gene transfer—such as physical, biological (viral vectors), and biomaterial (non-viral vectors) transfection methods—have been developed [3,5,6]. Physical methods involve the direct insertion of genes into the cells and can be categorized into mechanical approaches
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