Increase in transgene expression by pluronic L64-mediated endosomal/lysosomal escape through its membrane-disturbing action

ACS Applied Materials & Interfaces
Jianlin ChenZhongwei Gu

Abstract

For efficient transgene delivery and expression, internalized nucleic acids should quickly escape from cellular endosomes and lysosomes to avoid enzymatic destruction and degradation. Here, we report a novel strategy for safe and efficient endosomal/lysosomal escape of transgenes mediated by Pluronic L64, a neutral amphiphilic triblock copolymer. L64 enhanced the permeability of biomembranes by structural disturbance and pore formation in a concentration- and time-dependent manner. When applied at optimal concentration, it rapidly reached the endosome/lysosome compartments, where it facilitated escape of the transfection complex from the compartments and dissociation of the complex. Therefore, when applied properly, L64 not only significantly increased polyethylenimine- and liposome-mediated transgene expression, but also decreased the cytotoxicity occasioned by transfection process. Our studies revealed the function and mechanism of neutral amphiphilic triblock copolymer as potent mediator for safe and efficient gene delivery.

References

Jul 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·E WagnerM L Birnstiel
Jan 1, 1986·Annual Review of Biochemistry·I MellmanA Helenius
Aug 1, 1995·Proceedings of the National Academy of Sciences of the United States of America·O BoussifJ P Behr
Jun 6, 2000·Advanced Drug Delivery Reviews·C W Pouton, L W Seymour
Aug 19, 2000·BioTechniques·A ColosimoD C Gruenert
Sep 22, 2000·Trends in Biotechnology·S M Moghimi, A C Hunter
Nov 22, 2001·Bioconjugate Chemistry·C Y CheungA S Hoffman
Mar 19, 2002·Advanced Drug Delivery Reviews·Alexander V KabanovValery Alakhov
Apr 16, 2002·Current Opinion in Biotechnology·Mark E Davis
Mar 27, 2004·European Biophysics Journal : EBJ·Jan SunPeter Pohl
Mar 19, 2005·The Journal of Gene Medicine·Gretchen L Lorenzi, Kyung-Dall Lee
Jun 21, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Joanna RejmanMassimo Conese
Jul 30, 2005·Nature Reviews. Drug Discovery·Daniel W PackPatrick S Stayton
Sep 2, 2005·Nature Cell Biology·Christian de Duve
Sep 13, 2005·Journal of Controlled Release : Official Journal of the Controlled Release Society·Zhihui YangAlexander Kabanov
Oct 4, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Srikanth SriadibhatlaAlexander Kabanov
Mar 2, 2006·Pharmacological Reviews·Ikramy A KhalilHideyoshi Harashima
Mar 9, 2006·Nature Reviews. Drug Discovery·Enrico MastrobattistaDaan J A Crommelin
Mar 21, 2006·Journal of Controlled Release : Official Journal of the Controlled Release Society·Sabine BoeckleErnst Wagner
Nov 18, 2006·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Antoine KichlerBurkhard Bechinger
Jul 31, 2007·The Journal of Physical Chemistry. B·Jocelyne Gau-RacineLoïc Auvray
Aug 25, 2007·Journal of Controlled Release : Official Journal of the Controlled Release Society·Shubiao ZhangBaichao Ma
Mar 14, 2008·Angewandte Chemie·Wolfgang H Binder
Jun 7, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Elena V Batrakova, Alexander V Kabanov
Jul 29, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Chao Lin, Johan F J Engbersen
Oct 16, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·A del Pozo-RodríguezJ L Pedraz
Dec 5, 2008·Chemical Reviews·Meredith A Mintzer, Eric E Simanek
Jan 10, 2009·Nature Protocols·Masoud Soleimani, Samad Nadri
Jun 18, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Hansjörg HufnagelFlorian Hollfelder
Mar 17, 2010·Journal of Controlled Release : Official Journal of the Controlled Release Society·Gaurav SahayAlexander V Kabanov
Apr 24, 2013·Nature Reviews. Molecular Cell Biology·Carmine SettembreAndrea Ballabio
Aug 7, 2013·Journal of Molecular Cell Biology·Hanna AppelqvistKarin Öllinger
Nov 12, 2013·Critical Reviews in Oncology/hematology·Nian-feng SunSan-yuan Hu

❮ Previous
Next ❯

Citations

Sep 14, 2016·Langmuir : the ACS Journal of Surfaces and Colloids·Nazar Ileri ErcanRoland Faller
Jan 10, 2020·Macromolecular Bioscience·Bazoly RasolonjatovoPhilippe Guégan
Jun 7, 2017·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Mengjun ZhangDawei Chen
May 23, 2021·Advanced Healthcare Materials·Hang WuGuangxi Zhai
Apr 26, 2018·Langmuir : the ACS Journal of Surfaces and Colloids·Wantong LiKongshuang Zhao
Aug 25, 2021·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Rangrang FanGang Guo

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

© 2021 Meta ULC. All rights reserved