Polymeric Gene Carriers

Abstract

Polymeric gene carriers are a potential alternative to using viral vectors. Polymeric carriers have relatively low immunogenicity and cytotoxicity. In addition, polymeric carriers can accommodate large-size DNA, be conjugated with appropriate functionalities, and be administered repeatedly. In spite of these advantages, polymeric gene carriers have some limitations, such as low gene transfection efficiencies and relatively short duration of gene expression. Therefore, extensive research has been conducted toward the development of efficient polymeric carriers. In this review, we discuss current problems associated with polymeric gene carriers and various strategies against transfection barriers in particular, gene stabilization and protection, cellular targeting, endosomal escaping, nuclear targeting, unpackaging, and biocompatibility. Finally, requirements for future polymeric gene carriers are considered. With all these ongoing efforts, polymeric carriers have become one of the promising gene delivery methods for human gene therapy.

In vitro and in vivo effects of polyethylene glycol (PEG)-modified lipid in DOTAP/cholesterol-mediated gene transfection

“…[1,[2][3] H]-Cholesteryl Hexadecyl Ether ( 3 H-CHE) was purchased from Perkin Elmer (Skovlunde, Denmark). High quality plasmids: pCMV-LUC (sequence available upon request) and pEGFP-N1 (Clontech, Mountain View, CA, USA) preparations were made with the endo-free Giga kit from Qiagen GmbH (Hilden, Germany) according to the manufacturer's instructions.…”

Intelligent Polymeric Nanocarriers Responding to Physical or Biological Signals: A New Paradigm of Cytosolic Drug Delivery for Tumor Treatment

“…It was noted that drug carriers sequestrated into early endosomes after FR-mediated endocytosis responded to endosomal pH and released encapsulated anticancer drugs (e.g., doxorubicin: DOX) into the cytoplasm [27][28][29]. It appeared that the protonation of polyHis at endosomal pH resulted in the destabilization of the endosomal membrane, which is associated with the proton sponge effect [30]. It has been well established that the vacuolar ATPase-H + pumps in endosomal membranes modulate proton transfer from the cytoplasm to endosomal compartments [30].…”

“…It appeared that the protonation of polyHis at endosomal pH resulted in the destabilization of the endosomal membrane, which is associated with the proton sponge effect [30]. It has been well established that the vacuolar ATPase-H + pumps in endosomal membranes modulate proton transfer from the cytoplasm to endosomal compartments [30]. If certain materials with protonatable groups are entrapped within these acidic compartments, the transferred protons will be captured by protonatable moieties.…”

Apoptosis Induced by Polyethylenimine/DNA Complex in Polymer Mediated Gene Delivery

“…5,6 Poly-L-lysine (PLL) and polyethylenimine (PEI) have been commonly used as polymeric vectors. 7 PEI has higher transfection efficiency than PLL, due to proton sponge effect. 8,9 PEI and its derivatives have been investigated for various gene delivery applications.…”