Nonviral approaches for targeted delivery of plasmid DNA and oligonucleotide

Kawakami, Shigeru; Higuchi, Yuriko; Hashida, Mitsuru

doi:10.1002/jps.21024

Cited by 127 publications

(84 citation statements)

References 138 publications

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“…Results of this study highlight the importance of promoting non-viral gene transfer by alternative methods. Currently sonoporation or electroporation seem to be the most promising strategies in terms of safety, efficacy and minimal invasiveness [9,[29][30][31]. Further studies are needed to clarify if those strategies are capable to increase bone growth in a clinical relevant segmental bone defect model.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of fibrin-based gene-activated matrices for BMP2/7 plasmid codelivery in a rat nonunion model

Kaipel

Schützenberger

Hofmann

et al. 2014

International Orthopaedics (SICOT)

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PURPOSE: Treatment of large segmental bone defects still is a challenge in clinical routine.Application of Gene-activated matrices (GAMs) based on fibrin, BMP 2/7 plasmids and nonviral transfection reagents (cationic polymers) could be an innovative treatment strategy to overcome this problem.The aim of this study was to determine the therapeutic efficacy of fibrin GAMs with or without additional transfection reagents for bone morphogenic protein (BMP)2 and BMP7 plasmid co-delivery in a rat femur non-union model. METHODS:In this experimental study a critical size femoral defect was created in 27 rats. At 4 weeks after the surgery animals were separated into 4 groups and underwent a second operation. Fibrin clots containing BMP2 and BMP7 plasmids with and without cationic polymer were implanted into the femoral defect. Fibrin clots containing recombinant human (rh) BMP2 served as positive and clots without supplement as negative controls.RESULTS: At 8 weeks animals which received GAMs containing the cationic polymer and BMP 2/7 plasmids showed decreased bone volume compared to animals treated with GAMs and BMP2/7 only. Application of BMP2 and BMP7 plasmids in fibrin GAMs without cationic polymer lead to variable results. Animals which received rhBMP 2 protein showed increased bone volume and osseous unions were achieved in 2 out of 6 animals.2 CONCLUSIONS: Cationic polymers decrease therapeutic efficiency of fibrin GAM based BMP2/7 plasmid co-delivery in bone regeneration. Non-viral gene transfer of BMP2/7 plasmids needs alternative promoters (e.g. by sonoporation, electroporation) to promise beneficial clinical effects.

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Section: Discussionmentioning

confidence: 99%

Evaluation of fibrin-based gene-activated matrices for BMP2/7 plasmid codelivery in a rat nonunion model

Kaipel

Schützenberger

Hofmann

et al. 2014

International Orthopaedics (SICOT)

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“…This strategy has some advantages: 1) the possibility to express genes in a relatively short period of time, thus avoiding compensatory mechanisms or effects during the development, 2) the possibility to target specific tissues, and 3) limited cost. For delivery of a gene into the organ of a live animal, there are two main approaches: the use of viral vectors and the use of plasmid DNA (20). Although viral vectors are the most efficient vehicles for gene transfer, the targeted tissue often develops immunopathological reactions to the virus (22,39).…”

mentioning

confidence: 99%

Expression of plasmid DNA in the salivary gland epithelium: novel approaches to study dynamic cellular processes in live animals

Šrámková¹,

Masedunskas²,

Parente³

et al. 2009

American Journal of Physiology-Cell Physiology

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The ability to dynamically image cellular and subcellular structures in a live animal and to target genes to a specific cell population in a living tissue provides a unique tool to address many biological questions in the proper physiological context. Here, we describe a powerful approach that is based on the use of rat submandibular salivary glands, which offer the possibility to easily perform intravital imaging and deliver molecules from the oral cavity, and plasmid DNA, which offers the advantage of rapid manipulations. We show that, under different experimental conditions, a reporter molecule can be rapidly expressed in specific compartments of the glands: 1) in the intercalated ducts, when plasmid DNA is administered alone, and 2) in granular ducts, striated ducts, and, to a lesser extent, acini, when plasmid DNA is mixed with replication-deficient adenovirus subtype 5 particles. Remarkably, we also found that gene expression can be directed to acinar cells when plasmid DNA is administered during isoproterenol-stimulated exocytosis, suggesting a novel mechanism of plasmid internalization regulated by compensatory endocytosis. Finally, as a practical application of these strategies, we show how the expression of fluorescently tagged molecules enables the study of the dynamics of various organelles in live animals at a resolution comparable to that achieved in cell cultures.

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“…The basic interaction between polymers and DNA is electrostatic, as the positive groups on the polymer are attracted to the negatively charged phosphate groups in the nucleic acids. Linear polymers investigated include poly-L-lysine, poly-L-ornithine, polyethyleneimine (PEI), and poly(DL-lactide-co-glycolide) (PLGA) [5,14,16]. Dextrans and spermines have also been investigated as carriers and/or condensation agents [17][18][19][20].…”

Section: Polymer-based Vectorsmentioning

confidence: 99%

“…In general, polymer-nucleic acid complexation can be considered analogous to histone winding of DNA into chromosomes. The efficiency of polymers in condensing DNA depends partly on the polymeric structure and molecular weight, as well as the charge ratio between the negatively charged phosphate groups on the DNA and the positively charged groups in the polymers [16,[21][22][23]. …”

mentioning

confidence: 99%

Non‐viral gene therapy for myocardial engineering

Holladay

O’Brien

Pandit

2010

WIREs Nanomed Nanobiotechnol

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Despite significant advances in surgical and pharmacological techniques, myocardial infarction remains the main cause of morbidity in the developed world because no remedy has been found for the regeneration of infarcted myocardium. Once the blood supply to the area in question is interrupted, the inflammatory cascade, among other mechanisms, results in the damaged tissue becoming a scar. The goals of cardiac gene therapy are essentially to minimize damage, to promote regeneration or some combination thereof. While the vector is, in theory, less important than the gene being delivered, the choice of vector can have a significant impact. Viral therapies can have very high transfection efficiencies, but disadvantages include immunogenicity, retroviralmediated insertional mutagenesis and the expense and difficulty of manufacture. For these reasons, researchers have focused on non-viral gene therapy as an alternative. In this review, naked plasmid delivery, or the delivery of complexed plasmids, and cellmediated gene delivery to the myocardium will be reviewed. Pre-clinical and clinical trials in the cardiac tissue will form the core of the discussion. While unmodified stem cells are sometimes considered therapeutic vectors based on paracrine mechanisms of action basic understanding is limited. Thus, only genetically modified cells will be discussed as cell-mediated gene therapy.Ischemic heart disease, which includes acute damage due to myocardial infarction (MI) and chronic damage due to atherosclerotic narrowing of vessels, accounts for 35% of deaths reported in the United States every year [1]. MI, which is literally the death of cardiac tissue due to lack of 2 oxygen supply, is the result of the occlusion of a coronary artery. Within a few hours of interrupted blood supply, affected cardiomyocytes die. While the body has adaptive mechanisms, such as hypertrophy of the undamaged cardiac muscle and the development of collateral blood supply to minimize the damage, ischemic heart disease remains the most common cause of death in developed countries [2].The delivery of plasmid DNA to the myocardium is a complicated problem as the transfection efficiency of unmodified DNA is quite low, but complexation with agents designed to improve transfection can increase the cytotoxicity of the treatment [3]. Delivery of uncomplexed plasmid DNA is conceptually the simplest gene delivery technique, but these plasmids have extremely low transfection efficiencies in vitro and are not particularly effective in vivo. Compared to viral vectors, transgene expression is almost negligible and the expression time is also very limited [4]. However, there are significant advantages in using plasmids instead of viruses, such as ease of preparation (large and small scale), very low immunogenicity (as there are essentially no protein or membrane components in the plasmid), capacity for long term storage, ease of recombinant manipulation and much larger expression cassettes [4]. A variety of non-viral techniques are available to improve...

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Nonviral approaches for targeted delivery of plasmid DNA and oligonucleotide

Cited by 127 publications

References 138 publications

Evaluation of fibrin-based gene-activated matrices for BMP2/7 plasmid codelivery in a rat nonunion model

Evaluation of fibrin-based gene-activated matrices for BMP2/7 plasmid codelivery in a rat nonunion model

Expression of plasmid DNA in the salivary gland epithelium: novel approaches to study dynamic cellular processes in live animals

Non‐viral gene therapy for myocardial engineering

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