scholarly journals The Development of Functional Non-Viral Vectors for Gene Delivery

2019 ◽  
Vol 20 (21) ◽  
pp. 5491 ◽  
Author(s):  
Patil ◽  
Gao ◽  
Lin ◽  
Li ◽  
Dang ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Targeted Delivery ◽  
Viral Vectors ◽  
High Efficiency ◽  
Transfection Efficiency ◽  
Cationic Lipids ◽  
Gene Vectors ◽  
Potential Applications ◽  
Low Toxicity ◽  
Low Cytotoxicity

Gene therapy is manipulation in/of gene expression in specific cells/tissue to treat diseases. This manipulation is carried out by introducing exogenous nucleic acids, such as DNA or RNA, into the cell. Because of their negative charge and considerable larger size, the delivery of these molecules, in general, should be mediated by gene vectors. Non-viral vectors, as promising delivery systems, have received considerable attention due to their low cytotoxicity and non-immunogenicity. As research continued, more and more functional non-viral vectors have emerged. They not only have the ability to deliver a gene into the cells but also have other functions, such as the performance of fluorescence imaging, which aids in monitoring their progress, targeted delivery, and biodegradation. Recently, many reviews related to non-viral vectors, such as polymers and cationic lipids, have been reported. However, there are few reviews regarding functional non-viral vectors. This review summarizes the common functional non-viral vectors developed in the last ten years and their potential applications in the future. The transfection efficiency and the transport mechanism of these materials were also discussed in detail. We hope that this review can help researchers design more new high-efficiency and low-toxicity multifunctional non-viral vectors, and further accelerate the progress of gene therapy.

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 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 Delivery System and Targeted Bone Disease Therapy

2019 ◽  
Vol 20 (3) ◽  
pp. 565 ◽  
Author(s):  
Abdul Qadir ◽  
Yongguang Gao ◽  
Patil Suryaji ◽  
Ye Tian ◽  
Xiao Lin ◽  
...  
Keyword(s):  
Delivery System ◽  
Targeted Delivery ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Calcium Phosphates ◽  
Delivery Systems ◽  
Cationic Lipids ◽  
Cationic Polymers ◽  
Bone Disorders ◽  
High Doses

Skeletal systems provide support, movement, and protection to the human body. It can be affected by several life suffering bone disorders such as osteoporosis, osteoarthritis, and bone cancers. It is not an easy job to treat bone disorders because of avascular cartilage regions. Treatment with non-specific drug delivery must utilize high doses of systemic administration, which may result in toxicities in non-skeletal tissues and low therapeutic efficacy. Therefore, in order to overcome such limitations, developments in targeted delivery systems are urgently needed. Although the idea of a general targeted delivery system using bone targeting moieties like bisphosphonates, tetracycline, and calcium phosphates emerged a few decades ago, identification of carrier systems like viral and non-viral vectors is a recent approach. Viral vectors have high transfection efficiency but are limited by inducing immunogenicity and oncogenicity. Although non-viral vectors possess low transfection efficiency they are comparatively safe. A number of non-viral vectors including cationic lipids, cationic polymers, and cationic peptides have been developed and used for targeted delivery of DNA, RNA, and drugs to bone tissues or cells with successful consequences. Here we mainly discuss such various non-viral delivery systems with respect to their mechanisms and applications in the specific targeting of bone tissues or cells. Moreover, we discuss possible therapeutic agents that can be delivered against various bone related disorders.

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...

scholarly journals Facile Synthesis of N-Doped Graphene Quantum Dots as Novel Transfection Agents for mRNA and pDNA

Nanomaterials ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2816
Author(s):  
Minchul Ahn ◽  
Jaekwang Song ◽  
Byung Hee Hong
Keyword(s):  
Gene Therapy ◽  
Quantum Dots ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Graphene Quantum Dots ◽  
Target Cells ◽  
Ribonucleic Acids ◽  
Efficient Delivery ◽  
Doped Graphene ◽  
Low Toxicity

In the wake of the coronavirus disease 2019 (COVID-19) pandemic, global pharmaceutical companies have developed vaccines for the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Some have adopted lipid nanoparticles (LNPs) or viral vectors to deliver the genes associated with the spike protein of SARS-CoV-2 for vaccination. This strategy of vaccination by delivering genes to express viral proteins has been successfully applied to the mRNA vaccines for COVID-19, and is also applicable to gene therapy. However, conventional transfection agents such as LNPs and viral vectors are not yet sufficient to satisfy the levels of safety, stability, and efficiency required for the clinical applications of gene therapy. In this study, we synthesized N-doped graphene quantum dots (NGQDs) for the transfection of various genes, including messenger ribonucleic acids (mRNAs) and plasmid deoxyribonucleic acids (pDNAs). The positively charged NGQDs successfully formed electrostatic complexes with negatively charged mRNAs and pDNAs, and resulted in the efficient delivery and transfection of the genes into target cells. The transfection efficiency of NGQDs is found to be comparable to that of commercially available LNPs. Considering their outstanding stability even at room temperature as well as their low toxicity, NGQDs are expected to be novel universal gene delivery platforms that can outperform LNPs and viral vectors.

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.

scholarly journals Сationic liposomes as delivery systems for nucleic acids

2020 ◽  
Vol 15 (1) ◽  
pp. 7-27
Author(s):  
A. A. Mikheev ◽  
E. V. Shmendel ◽  
E. S. Zhestovskaya ◽  
G. V. Nazarov ◽  
M. A. Maslov
Keyword(s):  
Gene Therapy ◽  
Nucleic Acids ◽  
Serum Proteins ◽  
Transfection Efficiency ◽  
Biological Fluids ◽  
Genetic Material ◽  
Cationic Liposomes ◽  
Delivery Systems ◽  
Cationic Lipids

Objectives. Gene therapy is based on the introduction of genetic material into cells, tissues, or organs for the treatment of hereditary or acquired diseases. A key factor in the success of gene therapy is the development of delivery systems that can efficiently transfer genetic material to the place of their therapeutic action without causing any associated side effects. Over the past 10 years, significant effort has been directed toward creating more efficient and biocompatible vectors capable of transferring nucleic acids (NAs) into cells without inducing an immune response. Cationic liposomes are among the most versatile tools for delivering NAs into cells; however, the use of liposomes for gene therapy is limited by their low specificity. This is due to the presence of various biological barriers to the complex of liposomes with NA, including instability in biological fluids, interaction with serum proteins, plasma and nuclear membranes, and endosomal degradation. This review summarizes the results of research in recent years on the development of cationic liposomes that are effective in vitro and in vivo. Particular attention is paid to the individual structural elements of cationic liposomes that determine the transfection efficiency and cytotoxicity. The purpose of this review was to provide a theoretical justification of the most promising choice of cationic liposomes for the delivery of NAs into eukaryotic cells and study the effect of the composition of cationic lipids (CLs) on the transfection efficiency in vitro.Results. As a result of the analysis of the related literature, it can be argued that one of the most promising delivery systems of NAs is CL based on cholesterol and spermine with the addition of a helper lipid DOPE. In addition, it was found that varying the composition of cationic liposomes, the ratio of CL to NA, or the size and zeta potential of liposomes has a significant effect on the transfection efficiency.Conclusions. Further studies in this direction should include optimization of the conditions for obtaining cationic liposomes, taking into account the physicochemical properties and established laws. It is necessary to identify mechanisms that increase the efficiency of NA delivery in vitro by searching for optimal structures of cationic liposomes, determining the ratio of lipoplex components, and studying the delivery efficiency and properties of multicomponent liposomes.

Bio-inspired gene carriers with low cytotoxicity constructed via the assembly of dextran nanogels and nano-coacervates

Nanomedicine ◽  
2020 ◽  
Vol 15 (13) ◽  
pp. 1285-1296 ◽  
Author(s):  
Chenglong Wang ◽  
Jiayi You ◽  
Miaomiao Gao ◽  
Peipei Zhang ◽  
Guoxiong Xu ◽  
...  
Keyword(s):  
Positive Charge ◽  
Transfection Efficiency ◽  
Gene Carrier ◽  
Gene Carriers ◽  
Environmentally Responsive ◽  
Potential Applications ◽  
Internal Peptide ◽  
The Common ◽  
Low Cytotoxicity ◽  
Peptide Gene

Aim: To achieve safe and biocompatible gene carriers. Materials & methods: A core/shell-structured hierarchical carrier with an internal peptide/gene coacervate ‘core’ and a dextran nanogel ‘shell’ on the surface has been designed. Results: The dextran nanogels shield coacervate (DNSC) can effectively condense genes and release them in reducing environments. The dextran nanogel-based ‘shell’ can effectively shield the positive charge of the peptide/gene coacervate ‘core’, thus reducing the side effects of cationic gene carriers. In contrast with the common nonviral gene carriers that had high cytotoxicities, the DNSC showed a high transfection efficiency while maintaining a low cytotoxicity. Conclusion: The DNSC provides an effective environmentally responsive gene carrier with potential applications in the fields of gene therapy and gene carrier development.

scholarly journals Layered Double Hydroxide as a Potent Non-viral Vector for Nucleic Acid Delivery Using Gene-Activated Scaffolds for Tissue Regeneration Applications

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1219
Author(s):  
Lara S. Costard ◽  
Domhnall C. Kelly ◽  
Rachael N. Power ◽  
Christopher Hobbs ◽  
Sonia Jaskaniec ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Layered Double Hydroxide ◽  
Viral Vectors ◽  
Viral Vector ◽  
Nucleic Acid Delivery ◽  
Safe Alternative ◽  
Transfection Efficacy ◽  
Mass Ratios ◽  
Low Cytotoxicity ◽  
Double Hydroxide

Nonviral vectors offer a safe alternative to viral vectors for gene therapy applications, albeit typically exhibiting lower transfection efficiencies. As a result, there remains a significant need for the development of a nonviral delivery system with low cytotoxicity and high transfection efficacy as a tool for safe and transient gene delivery. This study assesses MgAl-NO3 layered double hydroxide (LDH) as a nonviral vector to deliver nucleic acids (pDNA, miRNA and siRNA) to mesenchymal stromal cells (MSCs) in 2D culture and using a 3D tissue engineering scaffold approach. Nanoparticles were formulated by complexing LDH with pDNA, microRNA (miRNA) mimics and inhibitors, and siRNA at varying mass ratios of LDH:nucleic acid. In 2D monolayer, pDNA delivery demonstrated significant cytotoxicity issues, and low cellular transfection was deemed to be a result of the poor physicochemical properties of the LDH–pDNA nanoparticles. However, the lower mass ratios required to successfully complex with miRNA and siRNA cargo allowed for efficient delivery to MSCs. Furthermore, incorporation of LDH–miRNA nanoparticles into collagen-nanohydroxyapatite scaffolds resulted in successful overexpression of miRNA in MSCs, demonstrating the development of an efficacious miRNA delivery platform for gene therapy applications in regenerative medicine.

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