Language:

Polyplex Evolution: Understanding Biology, Optimizing Performance

Molecular therapy, 2017-07, Vol.25 (7), p.1476-1490 [Peer Reviewed Journal]

2017 The American Society of Gene and Cell Therapy ;Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved. ;2017. The American Society of Gene and Cell Therapy ;2017 The American Society of Gene and Cell Therapy. 2017 The American Society of Gene and Cell Therapy ;ISSN: 1525-0016 ;ISSN: 1525-0024 ;EISSN: 1525-0024 ;DOI: 10.1016/j.ymthe.2017.01.024 ;PMID: 28274797

Full text available

Citations Cited by

Actions
1. Add to My Research
2. Remove from My Research
3. E-mail
4. Print
5. Permalink
6. Citation
7. EasyBib
8. EndNote
9. RefWorks
10. Delicious
11. Export RIS
12. Export BibTeX

Title:
Polyplex Evolution: Understanding Biology, Optimizing Performance
Author: Hall, Arnaldur ; Lächelt, Ulrich ; Bartek, Jiri ; Wagner, Ernst ; Moghimi, Seyed Moein
Subjects: Animals ; Apoptosis ; Bioenergetics ; Cell Membrane - chemistry ; Cell Membrane - drug effects ; Cell Membrane - metabolism ; Chemical engineering ; Complement activation ; Complement Activation - drug effects ; complement system ; Complement System Proteins - genetics ; Complement System Proteins - metabolism ; Cytotoxicity ; Deoxyribonucleic acid ; DNA ; Efficiency ; Gene Expression Regulation - drug effects ; Gene therapy ; Gene Transfer Techniques ; Genetic Therapy ; Glycolysis ; Homeostasis ; Humans ; Investigations ; Medicin och hälsovetenskap ; Mitochondria ; Mitochondria - chemistry ; Mitochondria - drug effects ; Mitochondria - immunology ; Mitochondria - metabolism ; mitochondrion ; Molecular modelling ; Molecular weight ; Nucleic acids ; Oxidation-Reduction ; Polycations ; Polyethyleneimine - chemistry ; Polyethyleneimine - pharmacokinetics ; Polyethyleneimine - toxicity ; polyethylenimine ; Polymers ; polyplex ; Review ; Therapeutic applications ; Toll-like receptors ; Toll-Like Receptors - genetics ; Toll-Like Receptors - immunology ; Transfection ; Translation ; Vectors (Biology)
Is Part Of: Molecular therapy, 2017-07, Vol.25 (7), p.1476-1490
Description: Polyethylenimine (PEI) is a gold standard polycationic transfectant. However, the highly efficient transfecting activity of PEI and many of its derivatives is accompanied by serious cytotoxic complications and safety concerns at innate immune levels, which impedes the development of therapeutic polycationic nucleic acid carriers in general and their clinical applications. In recent years, the dilemma between transfection efficacy and adverse PEI activities has been addressed from in-depth investigations of cellular processes during transfection and elucidation of molecular mechanisms of PEI-mediated toxicity and translation of these integrated events to chemical engineering of novel PEI derivatives with an improved benefit-to-risk ratio. This review addresses these perspectives and discusses molecular events pertaining to dynamic and multifaceted PEI-mediated cytotoxicity, including membrane destabilization, mitochondrial dysfunction, and perturbations of glycolytic flux and redox homeostasis as well as chemical strategies for the generation of better tolerated polycations. We further examine the effect of PEI and its derivatives on complement activation and interaction with Toll-like receptors. These perspectives are intended to lay the foundation for an improved understanding of interlinked mechanisms controlling transfection and toxicity and their translation for improved engineering of polycation-based transfectants. [Display omitted] Polycations such as polyethylenimines (PEIs) are widely used as non-viral transfectants, but they often induce cytotoxicity and may trigger immune reactions. Here we examine and discuss molecular events pertaining to dynamic and multifaceted PEI-mediated cytotoxicity and immune system modulation and their translation for improved and safer engineering of polycation-based transfectants.
Publisher: United States: Elsevier Inc
Language: English
Identifier: ISSN: 1525-0016
ISSN: 1525-0024
EISSN: 1525-0024
DOI: 10.1016/j.ymthe.2017.01.024
PMID: 28274797
Source: Geneva Foundation Free Medical Journals at publisher websites
MEDLINE
PubMed Central
SWEPUB Freely available online
ProQuest Central

Back to results list


INSPIRE LIBRARY - TON DUC THANG UNIVERSITY	(84-028) 37 755 057	Feedback
19 Nguyen Huu Tho St. Dist.7, HCM	thuvien@tdtu.edu.vn	Feedback

Polyplex Evolution: Understanding Biology, Optimizing Performance

Searching Remote Databases, Please Wait