Abstract:Despite successful demonstration of linear polyethyleneimine (lPEI) as an effective carrier for a wide range of gene medicine, including DNA plasmids, small interfering RNAs, mRNAs, etc., and continuous improvement of the physical properties and biological performance of the polyelectrolyte complex nanoparticles prepared from lPEI and nucleic acids, there still exist major challenges to produce these nanocomplexes in a scalable manner, particularly for lPEI/DNA nanoparticles. This has significantly hindered th… Show more
“…Linear PEI is prepared as an effective carrier for a broad range of gene medicine, including DNA plasmids, small interfering RNAs, mRNAs. In addition, continuous improvement of the physical properties and biological function of polyelectrolyte complex achieved by nanoparticles made of LPEI and nucleic acids [29]. PEI is a polymer that contains amines isolated by ethylene groups and is a hydrophobic because of its rich ethylene-backbone.…”
Section: Peimentioning
confidence: 99%
“…In 2016, Santos et al, reported a flash nanocomplexation (FNC) method that continuously produces LPEI DNA/plasmid nanoparticles with a narrow size distribution using a confined impinging jet device. This method involves a combination of negatively charged DNA with positively charged LPEI in fast, high dynamic and homogeneous conditions, which produces complexes of poly-electrolytic nanoparticles with a narrow distribution of particle size and shape [29] (Figure 4). 10.1080/20022727.2018.1488497-F0004Figure 4.Schematic of the confined impinging jet (CIJ) device used to fabricate polyelectrolyte complex nanoparticles under rapid mixing conditions.…”
Section: Peimentioning
confidence: 99%
“…10.1080/20022727.2018.1488497-F0004Figure 4.Schematic of the confined impinging jet (CIJ) device used to fabricate polyelectrolyte complex nanoparticles under rapid mixing conditions. (Streams are loaded independently with PEI/DNA plasmid and PEI/DNA nanoparticles, and are placed in a small compartment prior to collection [29]. ).…”
Section: Peimentioning
confidence: 99%
“…(Streams are loaded independently with PEI/DNA plasmid and PEI/DNA nanoparticles, and are placed in a small compartment prior to collection [29]. ).…”
The meaning of gene therapy is the delivery of DNA or RNA to cells for the treatment or prevention of genetic disorders. The success rate of gene therapy depends on the progression and safe gene delivery system. The vectors available for gene therapy are divided into viral and non-viral systems. Viral vectors cause higher transmission efficiency and long gene expression, but they have major problems, such as immunogenicity, carcinogenicity, the inability to transfer large size genes and high costs. Non-viral gene transfer vectors have attracted more attention because they exhibit less toxicity and the ability to transfer large size genes. However, the clinical application of non-viral methods still faces some limitations, including low transmission efficiency and poor gene expression. In recent years, numerous methods and gene-carriers have been developed to improve gene transfer efficiency. The use of Polyethylenimine (PEI) based transfer of collaboration may create a new way of treating diseases and the combination of chemotherapy and gene therapy. The purpose of this paper is to introduce the PEI as an appropriate vector for the effective gene delivery.
“…Linear PEI is prepared as an effective carrier for a broad range of gene medicine, including DNA plasmids, small interfering RNAs, mRNAs. In addition, continuous improvement of the physical properties and biological function of polyelectrolyte complex achieved by nanoparticles made of LPEI and nucleic acids [29]. PEI is a polymer that contains amines isolated by ethylene groups and is a hydrophobic because of its rich ethylene-backbone.…”
Section: Peimentioning
confidence: 99%
“…In 2016, Santos et al, reported a flash nanocomplexation (FNC) method that continuously produces LPEI DNA/plasmid nanoparticles with a narrow size distribution using a confined impinging jet device. This method involves a combination of negatively charged DNA with positively charged LPEI in fast, high dynamic and homogeneous conditions, which produces complexes of poly-electrolytic nanoparticles with a narrow distribution of particle size and shape [29] (Figure 4). 10.1080/20022727.2018.1488497-F0004Figure 4.Schematic of the confined impinging jet (CIJ) device used to fabricate polyelectrolyte complex nanoparticles under rapid mixing conditions.…”
Section: Peimentioning
confidence: 99%
“…10.1080/20022727.2018.1488497-F0004Figure 4.Schematic of the confined impinging jet (CIJ) device used to fabricate polyelectrolyte complex nanoparticles under rapid mixing conditions. (Streams are loaded independently with PEI/DNA plasmid and PEI/DNA nanoparticles, and are placed in a small compartment prior to collection [29]. ).…”
Section: Peimentioning
confidence: 99%
“…(Streams are loaded independently with PEI/DNA plasmid and PEI/DNA nanoparticles, and are placed in a small compartment prior to collection [29]. ).…”
The meaning of gene therapy is the delivery of DNA or RNA to cells for the treatment or prevention of genetic disorders. The success rate of gene therapy depends on the progression and safe gene delivery system. The vectors available for gene therapy are divided into viral and non-viral systems. Viral vectors cause higher transmission efficiency and long gene expression, but they have major problems, such as immunogenicity, carcinogenicity, the inability to transfer large size genes and high costs. Non-viral gene transfer vectors have attracted more attention because they exhibit less toxicity and the ability to transfer large size genes. However, the clinical application of non-viral methods still faces some limitations, including low transmission efficiency and poor gene expression. In recent years, numerous methods and gene-carriers have been developed to improve gene transfer efficiency. The use of Polyethylenimine (PEI) based transfer of collaboration may create a new way of treating diseases and the combination of chemotherapy and gene therapy. The purpose of this paper is to introduce the PEI as an appropriate vector for the effective gene delivery.
“…Additionally, the biomanufacturing issue which involves the large‐scale production of these polymeric NPs and quality control must also be addressed. Recent studies suggest that flash nanocomplexation may be particularly suitable for the manufacturing of these NPs . It has been 20 years since the first report suggesting the feasibility of using nonviral vectors to generate a therapeutic effect through oral administration .…”
Efficient nonviral oral gene delivery offers an attractive modality for chronic protein replacement therapy. Herein, the oral delivery of insulin gene is reported by a nonviral vector comprising a copolymer with a high degree of substitution of branched polyethylenimine on chitosan (CS‐g‐bPEI). Protecting the plasmid from gastric acidic degradation and facilitating transport across the gut epithelium, the CS‐g‐bPEI/insulin plasmid DNA nanoparticles (NPs) can achieve systemic transgene expression for days. A single dose of orally administered NPs (600 µg plasmid insulin (pINS)) to diabetic mice can protect the animals from hyperglycemia for more than 10 d. Three repeated administrations spaced over a 10 d interval produce similar glucose‐lowering results with no hepatotoxicity detected. Positron‐emission‐tomography and computed‐tomography images also confirm the glucose utilization by muscle cells. While this work suggests the feasibility of basal therapy for diabetes mellitus, its significance lies in the demonstration of a nonviral oral gene delivery system that can impact chronic protein replacement therapy and DNA vaccination.
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