scholarly journals Injectable “nano-micron” combined gene-hydrogel microspheres for local treatment of osteoarthritis

2022 ◽  
Vol 14 (1) ◽  
Author(s):  
Bin Li ◽  
Fei Wang ◽  
Fangqiong Hu ◽  
Tao Ding ◽  
Ping Huang ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Articular Cartilage ◽  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Direct Injection ◽  
Local Treatment ◽  
Type Ii Collagen ◽  
Transfection Efficacy ◽  
Hydrogel Microspheres

AbstractSustained and controllable local gene therapy is a potential method for treating osteoarthritis (OA) through the delivery of therapeutic microRNAs (miRNAs) to targeted cells. However, direct injection of crude miRNAs for local gene therapy is limited due to its inadequate transfection efficiency, easy inactivation, and short half-life. Here, a multifunctional gene vector, arginine, histidine, and phenylalanine-modified generation 5 polyamidoamine (named G5-AHP), was employed to form G5-AHP/miR-140 nanoparticles by forming a complex with microRNA-140 (miR-140). Then, the nanoparticles were entrapped in hydrogel microspheres (MSs) to construct a “nano-micron” combined gene hydrogel to alleviate the degradation of articular cartilage. Monodisperse gelatin methacryloyl hydrogel MSs were produced under ultraviolet light using one-step innovative microfluidic technology. Evenly dispersed MSs showed better injectability in sustainable and matrix metalloproteinases (MMPs)-responsive degradation methods for local gene delivery. The G5-AHP/miR-140 nanoparticles released from the MSs exhibited high gene transfection efficacy and long-term bioactivity, facilitated endocytosis, and thus maintained the metabolic balance of cartilage matrix by promoting the expression of type II collagen and inhibiting the expression of a disintegrin and metalloproteinase with thrombospondin motifs-5 and MMP13 in chondrocytes. After injection of the “nano-micron” combined gene hydrogel into the articular cavity of the OA model, the gene hydrogel increased G5-AHP/miR-140 nanoparticle retention, prevented articular cartilage degeneration, and reduced osteophyte formation in a surgically induced mouse model of OA. The present study provides a novel cell-free approach to alleviate the progression of OA that shows potential for locally injected gene delivery systems.

scholarly journals Systemic gene delivery using lipid envelope systems and its potential in overcoming challenges

2021 ◽  
pp. 46-55
Author(s):  
Miteshkumar Malaviya ◽  
Milankumar Shiroya
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Prolonged Release ◽  
Safety And Efficacy ◽  
Specific Targeting ◽  
Transfection Efficacy ◽  
Gene Vectors ◽  
Systemic Gene Delivery

Nonviral vectors which offer a safer and versatile alternative to viral vectors have been developed to overcome problems caused by viral carriers. However, their transfection efficacy or level of expression is substantially lower than viral vectors. Among various nonviral gene vectors, lipid envelops systems are an ideal platform for the incorporation of safety and efficacy into a single delivery system. Emerging strategies for gene delivery using lipid-based delivery systems mainly aim at improving the transfection efficiency and potency while reducing toxicity, achieving prolonged release, cell-specific targeting, co-delivery of drug and gene. Earlier efforts to improve the transfection efficiency while overcoming the toxicity led to the need for preparing conjugates of lipids with polyamines. In this review, we highlight current lipidic vectors that have been developed for gene therapy, challenges, and their solutions.

Zn-promoted gene transfection efficiency for non-viral vectors: a mechanism study

2021 ◽  
Author(s):  
Xiao-Qi Yu ◽  
Rui-Mo Zhao ◽  
Yu Guo ◽  
Hui-Zhen Yang ◽  
Ji Zhang
Keyword(s):  
Gene Therapy ◽  
Nucleic Acid ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Viral Gene ◽  
Mechanism Study ◽  
High Affinity ◽  
Gene Vectors

The development of cationic non-viral gene vectors that may overcome the obstacles in gene delivery is of great significance to gene therapy. Metallic complexes with high affinity to nucleic acid...

Non-Viral Vectors for Gene Delivery

2018 ◽  
Vol 9 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Aparna Bansal ◽  
Himanshu
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Expression System ◽  
Target Cells ◽  
Specific Expression ◽  
Naked Dna

Introduction: Gene therapy has emerged out as a promising therapeutic pave for the treatment of genetic and acquired diseases. Gene transfection into target cells using naked DNA is a simple and safe approach which has been further improved by combining vectors or gene carriers. Both viral and non-viral approaches have achieved a milestone to establish this technique, but non-viral approaches have attained a significant attention because of their favourable properties like less immunotoxicity and biosafety, easy to produce with versatile surface modifications, etc. Literature is rich in evidences which revealed that undoubtedly, non–viral vectors have acquired a unique place in gene therapy but still there are number of challenges which are to be overcome to increase their effectiveness and prove them ideal gene vectors. Conclusion: To date, tissue specific expression, long lasting gene expression system, enhanced gene transfection efficiency has been achieved with improvement in delivery methods using non-viral vectors. This review mainly summarizes the various physical and chemical methods for gene transfer in vitro and in vivo.

Ultrasound molecular imaging-guided tumor gene therapy through dual-targeted cationic microbubbles

2021 ◽  
Vol 9 (7) ◽  
pp. 2454-2466
Author(s):  
Yingying Liu ◽  
Yuli Zhou ◽  
Jinfeng Xu ◽  
Hui Luo ◽  
Yao Zhu ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Molecular Imaging ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Tumor Gene Therapy ◽  
Ultrasound Molecular Imaging ◽  
Tumor Gene

A novel dual-targeted cationic microbubbles help to improve gene transfection efficiency.

scholarly journals Biodegradable PEI modified complex micelles as gene carriers with tunable gene transfection efficiency for ECs

2016 ◽  
Vol 4 (5) ◽  
pp. 997-1008 ◽  
Author(s):  
Juan Lv ◽  
Jing Yang ◽  
Xuefang Hao ◽  
Xiangkui Ren ◽  
Yakai Feng ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Vascular Grafts ◽  
Gene Carriers ◽  
Coronary Diseases ◽  
Potential Strategy ◽  
Complex Micelles

In recent years, gene therapy has evoked an increasing interest in clinical treatments of coronary diseases because it is a potential strategy to realize rapid endothelialization of artificial vascular grafts.

Self-assembling Janus dendritic polymer for gene delivery with low cytotoxicity and high gene transfection efficiency

2016 ◽  
Vol 4 (39) ◽  
pp. 6462-6467 ◽  
Author(s):  
Sheng-Gang Ding ◽  
Lei Yu ◽  
Long-Hai Wang ◽  
Lin-Ding Wang ◽  
Zhi-Qiang Yu ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Dendritic Polymer ◽  
Self Assembling ◽  
High Gene ◽  
Low Cytotoxicity

Polycations have high DNA condensing ability, low immunogenicity, and great adaptability, which make them promising for gene delivery.

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.

scholarly journals Non-viral Gene Therapy for Osteoarthritis

2021 ◽  
Vol 8 ◽  
Author(s):  
Ilona Uzieliene ◽  
Ursule Kalvaityte ◽  
Eiva Bernotiene ◽  
Ali Mobasheri
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Articular Chondrocytes ◽  
Transfection Efficiency ◽  
Viral Gene ◽  
Synovial Joint ◽  
Advantages And Disadvantages ◽  
Viral Gene Therapy ◽  
Viral Gene Delivery ◽  
Significant Effort

Strategies for delivering nucleic acids into damaged and diseased tissues have been divided into two major areas: viral and non-viral gene therapy. In this mini-review article we discuss the application of gene therapy for the treatment of osteoarthritis (OA), one of the most common forms of arthritis. We focus primarily on non-viral gene therapy and cell therapy. We briefly discuss the advantages and disadvantages of viral and non-viral gene therapy and review the nucleic acid transfer systems that have been used for gene delivery into articular chondrocytes in cartilage from the synovial joint. Although viral gene delivery has been more popular due to its reported efficiency, significant effort has gone into enhancing the transfection efficiency of non-viral delivery, making non-viral approaches promising tools for further application in basic, translational and clinical studies on OA. Non-viral gene delivery technologies have the potential to transform the future development of disease-modifying therapeutics for OA and related osteoarticular disorders. However, further research is needed to optimize transfection efficiency, longevity and duration of gene expression.

scholarly journals Interaction kinetics of peptide lipids-mediated gene delivery

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Yinan Zhao ◽  
Tianyi Zhao ◽  
Yanyan Du ◽  
Yingnan Cao ◽  
Yang Xuan ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Endosomal Escape ◽  
Late Endosomes ◽  
Key Factor ◽  
Interaction Kinetics ◽  
Dna Release

Abstract Background During the course of gene transfection, the interaction kinetics between liposomes and DNA is speculated to play very important role for blood stability, cellular uptake, DNA release and finally transfection efficiency. Results As cationic peptide liposomes exhibited great gene transfer activities both in vitro and in vivo, two peptide lipids, containing a tri-ornithine head (LOrn3) and a mono-ornithine head (LOrn1), were chosen to further clarify the process of liposome-mediated gene delivery in this study. The results show that the electrostatically-driven binding between DNA and liposomes reached nearly 100% at equilibrium, and high affinity of LOrn3 to DNA led to fast binding rate between them. The binding process between LOrn3 and DNA conformed to the kinetics equation: y = 1.663631 × exp (− 0.003427x) + 6.278163. Compared to liposome LOrn1, the liposome LOrn3/DNA lipoplex exhibited a faster and more uniform uptake in HeLa cells, as LOrn3 with a tri-ornithine peptide headgroup had a stronger interaction with the negatively charged cell membrane than LOrn1. The efficient endosomal escape of DNA from LOrn3 lipoplex was facilitated by the acidity in late endosomes, resulting in broken carbamate bonds, as well as the “proton sponge effect” of the lipid. Conclusions The interaction kinetics is a key factor for DNA transfection efficiency. This work provided insights into peptide lipid-mediated DNA delivery that could guide the development of the next generation of delivery systems for gene therapeutics.

scholarly journals Combining Hyaluronic Acid with Chitosan Enhances Gene Delivery

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Ana V. Oliveira ◽  
Diogo B. Bitoque ◽  
Gabriela A. Silva
Keyword(s):  
Hyaluronic Acid ◽  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Nonviral Vectors ◽  
Anionic Polymer ◽  
Dna Release

The low gene transfer efficiency of chitosan-DNA polyplexes is a consequence of their high stability and consequent slow DNA release. The incorporation of an anionic polymer is believed to loosen chitosan interactions with DNA and thus promote higher transfection efficiencies. In this work, several formulations of chitosan-DNA polyplexes incorporating hyaluronic acid were prepared and characterized for their gene transfection efficiency on both HEK293 and retinal pigment epithelial cells. The different polyplex formulations showed morphology, size, and charge compatible with a role in gene delivery. The incorporation of hyaluronic acid rendered the formulations less stable, as was the goal, but it did not affect the loading and protection of the DNA. Compared with chitosan alone, the transfection efficiency had a 4-fold improvement, which was attributed to the presence of hyaluronic acid. Overall, our hybrid chitosan-hyaluronic acid polyplexes showed a significant improvement of the efficiency of chitosan-based nonviral vectorsin vitro, suggesting that this strategy can further improve the transfection efficiency of nonviral vectors.

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