Polyplex: A Promising Gene Delivery System

In the past few years gene delivery system has gained a huge attention owing to its proved efficacy in several diseases especially in those caused by genetic and/oroncological malfunctioning. The effective gene delivery mainly depends on the carrier molecules that can ensure the safe and specific delivery of the nucleic acidmolecules. Viral vectors have been used for a longer period as the gene transfer vehicle. However, these viral vectors have potential immunological disadvantages that made them less preferred. Recently, non-viral vectors such as polyplexes have emerged as a promising alternative for viral vectors. Polyplexes are formed by conjugating a polymer with DNA and in maximum cases the cationic polymers are preferred over others. The structure and stability of the polyplexes depends on various factors. The ability of the polymer to condense the DNA mainly dictates the efficiency of the polyplex mediated transfection. In this review we are going to provide a framework for the synthesis and design of the polyplexes along with the structure and stability of the complexes pertaining to mechanism of action, characterization and therapeutic application, including polyethyleneimine mediated cytotoxicity as well as newer strategies for the generation of better polyplexes.

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Gene Transfer Using Nonviral Delivery Systems

Peritoneal Dialysis International ◽

10.1177/089686080602600603 ◽

2006 ◽

Vol 26 (6) ◽

pp. 633-640 ◽

Cited By ~ 13

Author(s):

Masanobu Miyazaki ◽

Yoko Obata ◽

Katsushige Abe ◽

Akira Furusu ◽

Takehiko Koji ◽

...

Keyword(s):

Gene Therapy ◽

Peritoneal Dialysis ◽

Gene Transfer ◽

Gene Delivery ◽

Delivery System ◽

Viral Vectors ◽

Nonviral Vectors ◽

Gene Delivery System ◽

Peritoneal Membrane ◽

Peritoneal Function

In peritoneal dialysis, loss of peritoneal function is a major factor in treatment failure. The alterations in peritoneal function are related to structural changes in the peritoneal membrane, including peritoneal sclerosis with increased extracellular matrix. Although peritoneal sclerosis is considered reversible to some extent through peritoneal rest, which improves peritoneal function and facilitates morphological changes, there has been no therapeutic intervention and no drug against the development and progression of peritoneal sclerosis. Using recent biotechnological advances in genetic engineering, a strategy based on genetic modification of the peritoneal membrane could be a potential therapeutic maneuver against peritoneal sclerosis and peritoneal membrane failure. Before this gene therapy may be applied clinically, a safe and effective gene delivery system as well as the selection of a gene therapy method must be established. There are presently two kinds of gene transfer vectors: viral and nonviral. Viral vectors are used mainly as a gene delivery system in the field of continuous ambulatory peritoneal dialysis research; however, they have several problems such as immunogenicity and toxicity. On the other hand, nonviral vectors have several advantages over viral vectors. We review here gene transfer using nonviral vector systems in the peritoneum: electroporation, liposomes, and cationized gelatin microspheres. In the field of peritoneal dialysis, gene therapy research using nonviral vectors is presently limited. Improvement in delivery methods together with an intelligent design of targeted genes has brought about large degrees of enhancement in the efficiency, specificity, and temporal control of nonviral vectors.

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Receptor-Mediated Gene Delivery into Antigen Presenting Cells Using Mannosylated Chitosan/DNA Nanoparticles

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2006.434 ◽

2006 ◽

Vol 6 (9) ◽

pp. 2796-2803 ◽

Cited By ~ 84

Author(s):

Tae Hee Kim ◽

Jae Woon Nah ◽

Myung-Haing Cho ◽

Tae Gwan Park ◽

Chong Su Cho

Keyword(s):

Gene Transfer ◽

Gene Delivery ◽

Delivery System ◽

Viral Vectors ◽

Antigen Presenting Cells ◽

Water Soluble ◽

Gene Delivery System ◽

Great Ability ◽

Safe Delivery ◽

Antigen Presenting

Dendritic cells (DCs) are professional antigen presenting cells that induce, sustain, and regulate immune responses. Gene modification of DCs is of particular interest for immunotherapy of diseases where the immunes system has failed or is abnormally regulated, such as in cancer or autoimmune disease. Gene transfer using non-viral vectors is a promising approach for the safe delivery of therapeutic DNA. Among various non-viral vectors, chitosan is considered to be a good candidate for gene delivery system, however, lack of cell specificity and low transfection of chitosan need to be overcome prior to clinical use. In this study, mannosylated chitosan (MC) was prepared to induce the receptor-mediated endocytosis and targeting into antigen presenting cells (APCs), especially DCs having mannose receptors. MC showed great ability to form complexes with DNA and showed suitable physicochemical properties for gene delivery system. It had low cytotoxicity and exhibited much enhanced gene transfer efficiency on the macrophage cell line than chitosan itself. Also, MC/DNA complex was more efficient for transferring IL-12 gene into DCs rather than water-soluble chitosan (WSC)/DNA one, which resulted in better induction of INF-γ from DCs. Therefore, MC is a promising gene delivery system for repeated administration to maintain sustained gene expression, thereby opening the possibility for immunotherapy.

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Physical Characterisation as an Insight into a Gene Delivery System Containing Cyclodextrins with Pluronic®-F127 and Folic acid as Non-Viral Vectors

Current Pharmaceutical Biotechnology ◽

10.2174/1389201015666140827102134 ◽

2014 ◽

Vol 15 (8) ◽

pp. 712-726

Author(s):

Matthew Eng ◽

Amal Elkordy ◽

Paul McCarron ◽

Eman Elkordy ◽

Ahmed Faheem

Keyword(s):

Folic Acid ◽

Gene Delivery ◽

Delivery System ◽

Viral Vectors ◽

Gene Delivery System ◽

Insight Into

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Minicircles for Investigating and Treating Arthritic Diseases

Pharmaceutics ◽

10.3390/pharmaceutics13050736 ◽

2021 ◽

Vol 13 (5) ◽

pp. 736

Author(s):

Yeri Alice Rim ◽

Yoojun Nam ◽

Narae Park ◽

Ji Hyeon Ju

Keyword(s):

Rheumatoid Arthritis ◽

Autoimmune Disease ◽

Gene Transfer ◽

Gene Delivery ◽

Viral Vectors ◽

Cartilage Tissue ◽

Minimal Size ◽

Gene Delivery System ◽

Related Disease ◽

Efficient Delivery

Gene delivery systems have become an essential component of research and the development of therapeutics for various diseases. Minicircles are non-viral vectors with promising characteristics for application in a variety of fields. With their minimal size, minicircles exhibit relatively high safety and efficient delivery of genes of interest into cells. Cartilage tissue lacks the natural ability to heal, making it difficult to treat osteoarthritis (OA) and rheumatoid arthritis (RA), which are the two main types of joint-related disease. Although both OA and RA affect the joint, RA is an autoimmune disease, while OA is a degenerative joint condition. Gene transfer using minicircles has also been used in many studies regarding cartilage and its diseased conditions. In this review, we summarize the cartilage-, OA-, and RA-based studies that have used minicircles as the gene delivery system.

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Local Gene Delivery System by Bubble Liposomes and Ultrasound Exposure into Joint Synovium

Journal of Drug Delivery ◽

10.1155/2011/203986 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 13

Author(s):

Yoichi Negishi ◽

Yuka Tsunoda ◽

Yoko Endo-Takahashi ◽

Yusuke Oda ◽

Ryo Suzuki ◽

...

Keyword(s):

Gene Expression ◽

Gene Transfer ◽

Gene Delivery ◽

Delivery System ◽

Imaging System ◽

Effective Means ◽

Gene Delivery System ◽

Highly Efficient ◽

Efficient Gene

Recently, we have developed novel polyethylene glycol modified liposomes (bubble liposomes; BL) entrapping an ultrasound (US) imaging gas, which can work as a gene delivery tool with US exposure. In this study, we investigated the usefulness of US-mediated gene transfer systems with BL into synoviocytes in vitro and joint synovium in vivo. Highly efficient gene transfer could be achieved in the cultured primary synoviocytes transfected with the combination of BL and US exposure, compared to treatment with plasmid DNA (pDNA) alone, pDNA plus BL, or pDNA plus US. When BL was injected into the knee joints of mice, and US exposure was applied transcutaneously to the injection site, highly efficient gene expression could be observed in the knee joint transfected with the combination of BL and US exposure, compared to treatment with pDNA alone, pDNA plus BL, or pDNA plus US. The localized and prolonged gene expression was also shown by an in vivo luciferase imaging system. Thus, this local gene delivery system into joint synovium using the combination of BL and US exposure may be an effective means for gene therapy in joint disorders.

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PREPARATION OF CALCIUM PHOSPHATE NANOPARTICLES AS NON-VIRAL VECTORS FOR GENE DELIVERY SYSTEM

Biomedical Engineering Applications Basis and Communications ◽

10.4015/s1016237217500272 ◽

2017 ◽

Vol 29 (04) ◽

pp. 1750027 ◽

Cited By ~ 1

Author(s):

Ko-Chung Yen ◽

I-Hua Chen ◽

Feng-Huei Lin

Keyword(s):

Gene Therapy ◽

Calcium Phosphate ◽

Gene Delivery ◽

Delivery System ◽

Viral Vectors ◽

Fluorescent Protein ◽

Molar Ratio ◽

Gene Delivery System ◽

Calcium Phosphate Nanoparticles

A major aim of gene therapy is the efficient and specific delivery of therapeutic gene into the desired target tissues. Development of reliable vectors is a major challenge in gene therapy. The aim of this study is to develop calcium phosphate nanoparticles as novel non-viral vectors for the gene delivery system. Calcium phosphate nanoparticles were prepared by water-in-oil microemulsion method with a water to surfactant molar ratio, Wo [Formula: see text] 2–10. This paper studies the design and synthesis of ultra-low size, highly monodispersed DNA doped calcium phosphate nanoparticles of size around 100[Formula: see text]nm in diameter. The structure of DNA-calcium phosphate nanocomplex observed by TEM was displayed as a shell-like structure. This study used pEGFP as a reporter gene. The encapsulating efficiency to encapsulate DNA inside the nanoparticles was greater than 80%. In the MTT test, both calcium phosphate nanoparticles and DNA-calcium phosphate nanocomplex have no negative effect for 293T cells. By gel electrophoresis of free and entrapped pEGFP DNA, the DNA encapsulated inside the nanoparticles was protected from the external DNaseI environment. In vitro transfection studies in 293T cell-line, the DNA-calcium phosphate nanocomplex could be used safely to transfer the encapsulated DNA into the 293T cells and expression green fluorescent protein. The characteristic of DNA-calcium phosphate nanocomplex to deliver DNA belongs to slow release. The property of DNA-calcium phosphate nanocomplex was fit in the requirement of non-viral vectors for the gene delivery system.

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Micelle-like luminescent nanoparticles as a visible gene delivery system with reduced toxicity

Journal of Materials Chemistry B ◽

10.1039/c5tb01225b ◽

2015 ◽

Vol 3 (42) ◽

pp. 8394-8400 ◽

Cited By ~ 5

Author(s):

Keni Yang ◽

Shengliang Li ◽

Shubin Jin ◽

Xiangdong Xue ◽

Tingbin Zhang ◽

...

Keyword(s):

Gene Delivery ◽

Delivery System ◽

Gene Transfection ◽

Gene Delivery System ◽

Cationic Polymers ◽

Luminescent Nanoparticles ◽

Reduced Toxicity

Luminescent nanoparticles (TPEI) were synthesized to tackle the undesired cytotoxicity of cationic polymers and were also used for visible gene transfection.

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Novel Gene Delivery System of Sendai Virus Transduced Human Peripheral Monocytes.

Blood ◽

10.1182/blood.v108.11.5482.5482 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5482-5482

Author(s):

Tomoko Tanaka ◽

Ryo Kurita ◽

Kashiya Takasugi ◽

Takafumi Nakamura ◽

Makoto Inoue ◽

...

Keyword(s):

Gene Therapy ◽

Gene Transfer ◽

Gene Delivery ◽

Delivery System ◽

Sendai Virus ◽

Transduction Efficiency ◽

Gene Delivery System ◽

Gene Transduction ◽

Novel Gene

Abstract Extensive monocytes extravasation is seen in infection sites, inflamed tissue and tumor tissues and exhibit a tissue-specific range of functions including phagocytosis, antigen presentation to T cells, and the release of a wide array of cytokines, chemokines, enzymes and nitrogen species. As monocytes have natural tropism to such tissues in each disease condition, these cells can be used as novel gene delivery system to cure the condition. On the other hand, as monocytes are quiescent cells, available gene transfer vectors are limited. Sendai virus (SeV) is a negative-strand RNA virus and has recently been used for the gene therapy vectors, SeV vectors (SeVV), for somatic gene therapy. This vector does not have potential of stable transformation of target cells because they generate no DNA intermediates and therefore are unable to integrate. Also, SeVV has been shown to ensure efficient expression of foreign genes in various types of tissues and can be used for gene transfer into monocytes. We first of all studied the gene transduction efficiency of SeVV into human peripheral blood CD 14 positive monocytes using GFP gene as a marker. About 82% of monocytes became GFP positive, whereas only 23% of lymphocytes and 1.8% of granulocytes became positive. The transduction efficiency was peaked at M.O.I.=1. The expression level was at least preserved for 24 hours in vitro. To do the in vivo preclinical experiments, we also transduced cDNA of GFP and GDNF (glial cell line-derived neurotrophic factor) into the peripheral monocytes of Macaca fascicularis monkey and high level expression of these genes were obtained. In vitro monocyte function after gene transduction are now under investigation. SeVV is considered to be promising gene transfer vector for primate monocytes.

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