scholarly journals Effect of Plasmid DNA Size on Chitosan or Polyethyleneimine Polyplexes Formulation

Polymers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 793
Author(s):  
J.F.A. Valente ◽  
P. Pereira ◽  
A. Sousa ◽  
J.A. Queiroz ◽  
F. Sousa
Keyword(s):  
Gene Delivery ◽  
Protein Expression ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
P53 Protein ◽  
Delivery Systems ◽  
Systematic Evaluation ◽  
P53 Expression ◽  
Complex Processes ◽  
Dna Size

Gene therapy could be simply defined as a strategy for the introduction of a functional copy of desired genes in patients, to correct some specific mutation and potentially treat the respective disorder. However, this straightforward definition hides very complex processes related to the design and preparation of the therapeutic genes, as well as the development of suitable gene delivery systems. Within non-viral vectors, polymeric nanocarriers have offered an ideal platform to be applied as gene delivery systems. Concerning this, the main goal of the study was to do a systematic evaluation on the formulation of pDNA delivery systems based on the complexation of different sized plasmids with chitosan (CH) or polyethyleneimine (PEI) polymers to search for the best option regarding encapsulation efficiency, surface charge, size, and delivery ability. The cytotoxicity and the transfection efficiency of these systems were accessed and, for the best p53 encoding pDNA nanosystems, the ability to promote protein expression was also evaluated. Overall, it was showed that CH polyplexes are more efficient on transfection when compared with the PEI polyplexes, resulting in higher P53 protein expression. Cells transfected with CH/p53-pDNA polyplexes presented an increase of around 54.2% on P53 expression, while the transfection with the PEI/p53-pDNA polyplexes resulted in a 32% increase.

NON-CONDENSING POLYMERIC GENE DELIVERY SYSTEMS: PRINCIPLES AND APPLICATIONS

Nano LIFE ◽  
2010 ◽  
Vol 01 (03n04) ◽  
pp. 219-237 ◽  
Author(s):  
SHARDOOL JAIN ◽  
HUSAIN ATTARWALA ◽  
MANSOOR AMIJI
Keyword(s):  
Gene Delivery ◽  
Targeted Delivery ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Contemporary Literature ◽  
Delivery Systems ◽  
Expression Of Genes ◽  
Cytoplasmic Dna ◽  
Polymeric Delivery ◽  
Systemic Gene Delivery

Gene therapy holds tremendous promise in prevention and treatment of diseases as the approach is based on regulating the expression of genes that are responsible for pathological conditions. The biggest bottleneck for gene delivery has been the development of safe and efficacious delivery systems. Although non-viral vectors are considered as much safer options than their viral counterparts, they suffer from low transfection efficiency. In this review, we highlight the role of non-condensing polymeric delivery systems for oral and systemic gene delivery. Using evidence from contemporary literature, non-condensing polymeric microparticle and nanoparticle systems afford physical encapsulation of the nucleic acid construct and can be engineered for targeted delivery to tissues and cells. Additionally, these systems have shown less toxicity and afford sustained cytoplasmic DNA delivery for efficient nuclear uptake and transfection for both DNA vaccines and therapeutic genes.

scholarly journals Nanoparticle-Mediated Interleukin-12 Cancer Gene Therapy

2010 ◽  
Vol 13 (3) ◽  
pp. 472 ◽  
Author(s):  
Crispin Dass ◽  
Somayeh Hallaj-Nezhadi ◽  
Farzaneh Lotfipour
Keyword(s):  
Gene Delivery ◽  
Viral Vectors ◽  
Safety Concern ◽  
Transfection Efficiency ◽  
Delivery Systems ◽  
Interleukin 12 ◽  
Viral Gene ◽  
Tumor Site ◽  
Antitumor Effects ◽  
Strong Immune Response

Interleukin-12 (Il-12) is a heterodimeric cytokine which has been proved to possess antitumor effects in various animal models via stimulating the immune system. The main problem associated with Il-12 protein delivery is its instability as well as cytotoxicity subsequent to systemic administration in rodents and in human clinical trials. However, gene delivery can be used to deliver genes of interest to the tumor site. Hence, a large number of studies have been undertaken to deliver genes of interest to the tumor site through viral or non-viral vectors. Viral DNA delivery systems suffer from safety concern due to the toxicity of the viruses and strong immune response; while non-viral gene delivery systems proffer lower transfection efficiency. Nevertheless, nanometer-size complex of therapeutic DNA may demonstrate more efficient for administration of therapeutic genes to solid tumors compared to administration of naked plasmid DNA. Nanoparticle-based gene delivery systems might be more pertinent, due to the enhanced tissue penetrability, improved cellular uptake. Il-12 gene delivery has already been reported with different nanoparticles containing DNA. This article provides a review on the in vivo and in vitro studies using various nanoparticles, for delivery of the Il-12 genes to neoplastic cells. The future of these promising approaches lies in the development of better techniques for preparing il-12 gene delivery systems with complete efficiency of viral vectors in addition to the highest safety for cancer patients.

Stepwise Development of Biomimetic Chimeric Peptides for Gene Delivery

2020 ◽  
Vol 27 (8) ◽  
pp. 698-710
Author(s):  
Roya Cheraghi ◽  
Mahboobeh Nazari ◽  
Mohsen Alipour ◽  
Saman Hosseinkhani
Keyword(s):  
Gene Delivery ◽  
Targeted Delivery ◽  
Viral Vectors ◽  
Large Scale ◽  
Transfection Efficiency ◽  
Cationic Lipids ◽  
Target Cells ◽  
Scale Production ◽  
Stepwise Development ◽  
Chimeric Peptides

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.

scholarly journals Highly Osmotic Oxidized Sucrose-Crosslinked Polyethylenimine for Gene Delivery Systems

Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 87
Author(s):  
Jaehong Park ◽  
Kyusik Kim ◽  
Sohee Jeong ◽  
Migyeom Lee ◽  
Tae-il Kim
Keyword(s):  
Gene Delivery ◽  
Reductive Amination ◽  
Transfection Efficiency ◽  
Delivery Systems ◽  
Buffering Capacity ◽  
Serum Stability ◽  
High Osmolality ◽  
Cox 2 ◽  
Serum Free Conditions ◽  
Positively Charged

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.

Adeno-Associated Viral Vectors for Gene Transfer and Gene Therapy

1999 ◽  
Vol 380 (6) ◽  
Author(s):  
H. Büeler
Keyword(s):  
Gene Expression ◽  
Gene Therapy ◽  
Gene Transfer ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Delivery Systems ◽  
Adeno Associated Virus ◽  
Viral Genes ◽  
Virus Recombinant

AbstractAdeno-associated virus (AAV) is a defective, non-pathogenic human parvovirus that depends for growth on coinfection with a helper adenovirus or herpes virus. Recombinant adeno-associated viruses (rAAVs) have attracted considerable interest as vectors for gene therapy. In contrast to other gene delivery systems, rAAVs lack all viral genes and show long-term gene expression

A dendritic catiomer with an MOF motif for the construction of safe and efficient gene delivery systems

2017 ◽  
Vol 5 (42) ◽  
pp. 8322-8329 ◽  
Author(s):  
Shuqi Dong ◽  
Qixian Chen ◽  
Wei Li ◽  
Zhu Jiang ◽  
Jianbiao Ma ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Gold Standard ◽  
Transfection Efficiency ◽  
A549 Cells ◽  
Delivery Systems ◽  
The Core ◽  
Efficient Gene

The dendritic catiomer using biocompatible Zr-MOFs as the core exhibited a markedly higher transfection efficiency and lower cytotoxicity than the commercial gold standard branched PEI25k in A549 cells.

Preparation, characterization and transfection efficiency of cationic PEGylated PLA nanoparticles as gene delivery systems

2007 ◽  
Vol 130 (2) ◽  
pp. 107-113 ◽  
Author(s):  
Jiji Chen ◽  
Buning Tian ◽  
Xiang Yin ◽  
Yanqiong Zhang ◽  
Duosha Hu ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Delivery Systems

scholarly journals Long-Circulating Polymeric Nanovectors for Tumor-Selective Gene Delivery

2005 ◽  
Vol 4 (6) ◽  
pp. 615-625 ◽  
Author(s):  
Sushma Kommareddy ◽  
Sandip B. Tiwari ◽  
Mansoor M. Amiji
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Viral Vectors ◽  
High Efficiency ◽  
Transfection Efficiency ◽  
The United States ◽  
Medical Intervention ◽  
Hydrophilic Polymers ◽  
Circulation Time ◽  
Viral Gene

Significant advances in the understanding of the genetic abnormalities that lead to the development, progression, and metastasis of neoplastic diseases has raised the promise of gene therapy as an approach to medical intervention. Most of the clinical protocols that have been approved in the United States for gene therapy have used the viral vectors because of the high efficiency of gene transfer. Conventional means of gene delivery using viral vectors, however, has undesirable side effects such as insertion of mutational viral gene into the host genome and development of replication competent viruses. Among non-viral gene delivery methods, polymeric nanoparticles are increasingly becoming popular as vectors of choice. The major limitation of these nanoparticles is poor transfection efficiency at the target site after systemic administration due to uptake by the cells of reticuloendothelial system (RES). In order to reduce the uptake by the cells of the RES and improve blood circulation time, these nanoparticles are coated with hydrophilic polymers such as poly(ethylene glycol) (PEG). This article reviews the use of such hydrophilic polymers employed for improving the circulation time of the nanocarriers. The mechanism of polymer coating and factors affecting the circulation time of these nanocarriers will be discussed. In addition to the long circulating property, modifications to improve the target specificity of the particles and the limitations of steric protection will be analyzed.

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