scholarly journals Micro cell vesicle technology (mCVT): a novel hybrid system of gene delivery for hard-to-transfect (HTT) cells

Nanoscale ◽  
2020 ◽  
Vol 12 (35) ◽  
pp. 18022-18030
Author(s):  
Yi-Hsuan Ou ◽  
Shui Zou ◽  
Wei Jiang Goh ◽  
Suet Yen Chong ◽  
Gopalakrishnan Venkatesan ◽  
...  

A new hybrid gene delivery platform (mCVT) remarkably improves the transfection efficiency of hard-to-transfect (HTT) cells, while preserving excellent biocompatibility.

Author(s):  
Yana V. Tarakanchikova ◽  
Dmitrii S. Linnik ◽  
Tatiana Mashel ◽  
Albert R. Muslimov ◽  
Sergey Pavlov ◽  
...  

2017 ◽  
Vol 5 (11) ◽  
pp. 2328-2336 ◽  
Author(s):  
Mathias Dimde ◽  
Falko Neumann ◽  
Felix Reisbeck ◽  
Svenja Ehrmann ◽  
Jose Luis Cuellar-Camacho ◽  
...  

An advanced cationic carrier system which combines high transfection efficiency with low cytotoxicity and a control over the release of the encapsulated genetic material by the reduction of the multivalent architecture upon pH triggered degradation was developed.


2020 ◽  
Vol 27 (8) ◽  
pp. 698-710
Author(s):  
Roya Cheraghi ◽  
Mahboobeh Nazari ◽  
Mohsen Alipour ◽  
Saman Hosseinkhani

Gene-based therapy largely relies on the vector type that allows a selective and efficient transfection into the target cells with maximum efficacy and minimal toxicity. Although, genes delivered utilizing modified viruses transfect efficiently and precisely, these vectors can cause severe immunological responses and are potentially carcinogenic. A promising method of overcoming this limitation is the use of non-viral vectors, including cationic lipids, polymers, dendrimers, and peptides, which offer potential routes for compacting DNA for targeted delivery. Although non-viral vectors exhibit reduced transfection efficiency compared to their viral counterpart, their superior biocompatibility, non-immunogenicity and potential for large-scale production make them increasingly attractive for modern therapy. There has been a great deal of interest in the development of biomimetic chimeric peptides. Biomimetic chimeric peptides contain different motifs for gene translocation into the nucleus of the desired cells. They have motifs for gene targeting into the desired cell, condense DNA into nanosize particles, translocate the gene into the nucleus and enhance the release of the particle into the cytoplasm. These carriers were developed in recent years. This review highlights the stepwise development of the biomimetic chimeric peptides currently being used in gene delivery.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 87
Author(s):  
Jaehong Park ◽  
Kyusik Kim ◽  
Sohee Jeong ◽  
Migyeom Lee ◽  
Tae-il Kim

In this work, highly osmotic oxidized sucrose-crosslinked polyethylenimine (SP2K) polymers were developed for gene delivery systems, and the transfection mechanism is examined. First, periodate-oxidized sucrose and polyethylenimine 2K (PEI2K) were crosslinked with various feed ratios via reductive amination. The synthesis was confirmed by 1H NMR and FTIR. The synthesized SP2K polymers could form positively charged (~40 mV zeta-potential) and nano-sized (150–200 nm) spherical polyplexes with plasmid DNA (pDNA). They showed lower cytotoxicity than PEI25K but concentration-dependent cytotoxicity. Among them, SP2K7 and SP2K10 showed higher transfection efficiency than PEI25K in both serum and serum-free conditions, revealing the good serum stability. It was found that SP2K polymers possessed high osmolality and endosome buffering capacity. The transfection experiments with cellular uptake inhibitors suggest that the transfection of SP2K polymers would progress by multiple pathways, including caveolae-mediated endocytosis. It was also thought that caveolae-mediated endocytosis of SP2K polyplexes would be facilitated through cyclooxygenase-2 (COX-2) expression induced by high osmotic pressure of SP2K polymers. Confocal microscopy results also supported that SP2K polyplexes would be internalized into cells via multiple pathways and escape endosomes efficiently via high osmolality and endosome buffering capacity. These results demonstrate the potential of SP2K polymers for gene delivery systems.


Author(s):  
Qingyao Kong ◽  
Yuanyuan Li ◽  
Jiping Yue ◽  
Xiaoyang Wu ◽  
Ming Xu

AbstractAlcohol use disorder (AUD) is one of the foremost public health problems. Alcohol is also frequently co-abused with cocaine. There is a huge unmet need for the treatment of AUD and/or cocaine co-abuse. We recently demonstrated that skin grafts generated from mouse epidermal stem cells that had been engineered by CRISPR-mediated genome editing could be transplanted onto mice as a gene delivery platform. Here, we show that expression of the glucagon-like peptide-1 (GLP1) gene delivered by epidermal stem cells attenuated development and reinstatement of alcohol-induced drug-taking and seeking as well as voluntary oral alcohol consumption. GLP1 derived from the skin grafts decreased alcohol-induced increase in dopamine levels in the nucleus accumbens. In exploring the potential of this platform in reducing concurrent use of drugs, we developed a novel co-grafting procedure for both modified human butyrylcholinesterase (hBChE)- and GLP1-expressing cells. Epidermal stem cell-derived hBChE and GLP1 reduced acquisition of drug-taking and toxicity induced by alcohol and cocaine co-administration. These results imply that cutaneous gene delivery through skin transplants may add a new option to treat drug abuse and co-abuse.


Polymers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 133
Author(s):  
Yu-Che Cheng ◽  
Shu-Lin Guo ◽  
Kun-Da Chung ◽  
Wei-Wen Hu

To sustain gene delivery and elongate transgene expression, plasmid DNA and cationic nonviral vectors can be deposited through layer-by-layer (LbL) assembly to form polyelectrolyte multilayers (PEMs). Although these macromolecules can be released for transfection purposes, their entanglement only allows partial delivery. Therefore, how to efficiently deliver immobilized genes from PEMs remains a challenge. In this study, we attempt to facilitate their delivery through the pretreatment of the external electrical field. Multilayers of polyethylenimine (PEI) and DNA were deposited onto conductive polypyrrole (PPy), which were placed in an aqueous environment to examine their release after electric field pretreatment. Only the electric field perpendicular to the substrate with constant voltage efficiently promoted the release of PEI and DNA from PEMs, and the higher potential resulted in the more releases which were enhanced with treatment time. The roughness of PEMs also increased after electric field treatment because the electrical field not only caused electrophoresis of polyelectrolytes and but also allowed electrochemical reaction on the PPy electrode. Finally, the released DNA and PEI were used for transfection. Polyplexes were successfully formed after electric field treatment, and the transfection efficiency was also improved, suggesting that this electric field pretreatment effectively assists gene delivery from PEMs and should be beneficial to regenerative medicine application.


2017 ◽  
Vol 246 ◽  
pp. 142-154 ◽  
Author(s):  
Jisang Yoo ◽  
DaeYong Lee ◽  
Vipul Gujrati ◽  
N. Sanoj Rejinold ◽  
Kamali Manickavasagam Lekshmi ◽  
...  

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Karl E. Kador ◽  
Anuradha Subramanian

Chitosan, a polyaminosaccharide, has been investigated for its use in the field of drug-delivery and biomaterial applications because of its natural biocompatibility and polycationic properties. Chemical modifications of chitosan have been attempted in an effort to increase the transfection efficiency with respect to gene delivery applications; however, it is unknown how these modifications affect the formation of the condensates. This study attempts to determine the effects of modification of the cationic center of chitosan on the ability to condense DNA. Specifically, electron-donating or -withdrawing groups were used as modifiers of the cationic charge on the chitosan backbone to stabilize the protonated form of chitosan, which is necessary to form condensates and increase the efficiency of the polymer to condense DNA by yielding condensates at a lower nitrogen to phosphorous (N : P) ratio. While an N : P ratio of 7 is needed to condense DNA with unmodified chitosan, phthalate-modified chitosan yielded condensates were obtained at an N : P ratio of 1.0.


2015 ◽  
Vol 1 (11) ◽  
pp. 1151-1162 ◽  
Author(s):  
Qi Lei ◽  
Hui-Zhen Jia ◽  
Wei-Hai Chen ◽  
Lei Rong ◽  
Si Chen ◽  
...  

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
S. Ghiamkazemi ◽  
A. Amanzadeh ◽  
R. Dinarvand ◽  
M. Rafiee-Tehrani ◽  
M. Amini

In this manuscript, we synthesized the potential non viral vector for gene delivery with proper transfection efficiency and low cytotoxicity. Polyethylenimine (PEI) is a well-known cationic polymer which has high positive surface charge for condensing plasmid DNA. However; it is highly cytotoxic in many cell lines because of the high surface charge, non-biodegradability and non-biocompatibility. To enhance PEI biodegradability, the graft copolymer “PEG-g-PEI” was synthesized. To target cancer liver cells, two targeting ligands folic acid and galactose (lactobionic acid) which are over expressed on human hepatocyte carcinoma were attached to graft copolymer and “FOL-PEG-g-PEI-GAL” copolymer was synthesized. Composition of this grafted copolymer was characterized using1H-NMR and FTIR spectra. The molecular weight and zeta potential of this copolymer was compared to PEI. The particle size and zeta potential of FOL-PEG-g-PEI-GAL/DNA complexes at various N/P ratio were measured using dynamic light scattering (DLS). Cytotoxicity of the copolymer was also studied in cultured HepG2 human hepatoblastoma cell line. The FOL-PEG-g-PEI-GAL/DNA complexes at various N/P ratios exhibited no cytotoxicity in HepG2 cell line compared to PEI 25K as a control. The novel copolymer showed enhanced biodegradability in physiological conditions in compared with PEI and targeted cultured HepG2 cells. More importantly, significant transfection efficiency was exhibited in cancer liver cells. Together, our results showed that “FOL-PEG-g-PEI-GAL” nanoparticals could be considered as a useful non-viral vector for targeted gene delivery.


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