scholarly journals Chitosan Oleate Coated PLGA Nanoparticles as siRNA Drug Delivery System

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1716
Author(s):  
Dalila Miele ◽  
Xin Xia ◽  
Laura Catenacci ◽  
Milena Sorrenti ◽  
Silvia Rossi ◽  
...  
Keyword(s):  
Viral Vectors ◽  
Insertional Mutagenesis ◽  
Plga Nanoparticles ◽  
Target Cells ◽  
Surface Charges ◽  
Covalent Bonds ◽  
Ribonucleic Acids ◽  
Cell Internalization ◽  
Efficient Delivery ◽  
Fast Release

Oligonucleotide therapeutics such as miRNAs and siRNAs represent a class of molecules developed to modulate gene expression by interfering with ribonucleic acids (RNAs) and protein synthesis. These molecules are characterized by strong instability and easy degradation due to nuclease enzymes. To avoid these drawbacks and ensure efficient delivery to target cells, viral and non-viral vectors are the two main approaches currently employed. Viral vectors are one of the major vehicles in gene therapy; however, the potent immunogenicity and the insertional mutagenesis is a potential issue for the patient. Non-viral vectors, such as polymeric nanocarriers, provide a safer and more efficient delivery of RNA-interfering molecules. The aim of this work is to employ PLGA core nanoparticles shell-coated with chitosan oleate as siRNA carriers. An siRNA targeted on HIV-1, directed against the viral Tat/Rev transcripts was employed as a model. The ionic interaction between the oligonucleotide’s moieties, negatively charged, and the positive surface charges of the chitosan shell was exploited to associate siRNA and nanoparticles. Non-covalent bonds can protect siRNA from nuclease degradation and guarantee a good cell internalization and a fast release of the siRNA into the cytosolic portion, allowing its easy activation.

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.

scholarly journals Lipid Nanoparticles as Delivery Systems for RNA-Based Vaccines

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 206 ◽  
Author(s):  
Basmah N. Aldosari ◽  
Iman M. Alfagih ◽  
Alanood S. Almurshedi
Keyword(s):  
Infectious Diseases ◽  
Immune Responses ◽  
Viral Vectors ◽  
Cost Effective ◽  
Lipid Nanoparticles ◽  
Target Cells ◽  
Efficient Delivery ◽  
Preclinical And Clinical Studies ◽  
Cancer Immunotherapies ◽  
Conventional Vaccine

There has been increased interest in the development of RNA-based vaccines for protection against various infectious diseases and also for cancer immunotherapies. Rapid and cost-effective manufacturing methods in addition to potent immune responses observed in preclinical and clinical studies have made mRNA-based vaccines promising alternatives to conventional vaccine technologies. However, efficient delivery of these vaccines requires that the mRNA be protected against extracellular degradation. Lipid nanoparticles (LNPs) have been extensively studied as non-viral vectors for the delivery of mRNA to target cells because of their relatively easy and scalable manufacturing processes. This review highlights key advances in the development of LNPs and reviews the application of mRNA-based vaccines formulated in LNPs for use against infectious diseases and cancer.

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.

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 Exosome/Liposome-like Nanoparticles: New Carriers for CRISPR Genome Editing in Plants

2021 ◽  
Vol 22 (14) ◽  
pp. 7456
Author(s):  
Mousa A. Alghuthaymi ◽  
Aftab Ahmad ◽  
Zulqurnain Khan ◽  
Sultan Habibullah Khan ◽  
Farah K. Ahmed ◽  
...  
Keyword(s):  
Genome Editing ◽  
Viral Vectors ◽  
Polymeric Materials ◽  
Inorganic Nanoparticles ◽  
Plant Genome ◽  
Delivery Methods ◽  
Detailed Consideration ◽  
Crispr System ◽  
Efficient Delivery ◽  
Low Cytotoxicity

Rapid developments in the field of plant genome editing using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) systems necessitate more detailed consideration of the delivery of the CRISPR system into plants. Successful and safe editing of plant genomes is partly based on efficient delivery of the CRISPR system. Along with the use of plasmids and viral vectors as cargo material for genome editing, non-viral vectors have also been considered for delivery purposes. These non-viral vectors can be made of a variety of materials, including inorganic nanoparticles, carbon nanotubes, liposomes, and protein- and peptide-based nanoparticles, as well as nanoscale polymeric materials. They have a decreased immune response, an advantage over viral vectors, and offer additional flexibility in their design, allowing them to be functionalized and targeted to specific sites in a biological system with low cytotoxicity. This review is dedicated to describing the delivery methods of CRISPR system into plants with emphasis on the use of non-viral vectors.

scholarly journals Minicircles for Investigating and Treating Arthritic Diseases

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 736
Author(s):  
Yeri Alice Rim ◽  
Yoojun Nam ◽  
Narae Park ◽  
Ji Hyeon Ju
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Disease ◽  
Gene Transfer ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Cartilage Tissue ◽  
Minimal Size ◽  
Gene Delivery System ◽  
Related Disease ◽  
Efficient Delivery

Gene delivery systems have become an essential component of research and the development of therapeutics for various diseases. Minicircles are non-viral vectors with promising characteristics for application in a variety of fields. With their minimal size, minicircles exhibit relatively high safety and efficient delivery of genes of interest into cells. Cartilage tissue lacks the natural ability to heal, making it difficult to treat osteoarthritis (OA) and rheumatoid arthritis (RA), which are the two main types of joint-related disease. Although both OA and RA affect the joint, RA is an autoimmune disease, while OA is a degenerative joint condition. Gene transfer using minicircles has also been used in many studies regarding cartilage and its diseased conditions. In this review, we summarize the cartilage-, OA-, and RA-based studies that have used minicircles as the gene delivery system.

Graphene: Insights on Biological, Radiochemical and Ecotoxicological Aspects

2021 ◽  
Vol 17 (1) ◽  
pp. 131-148
Author(s):  
Xing Haixia ◽  
Aline Oliveira da Silva de Barros ◽  
Francisco do Vale Chaves e Mello ◽  
Fan Sozzi-Guo ◽  
Cristina Müller ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Graphene Quantum Dots ◽  
Covalent Bonds ◽  
Cell Internalization ◽  
Functional Density Theory ◽  
Ecotoxicological Evaluation ◽  
Plasmatic Membrane ◽  
Low Toxicity ◽  
The Impact

Graphene, including graphene quantum dots, its oxide and unoxidized forms (pure graphene) have several properties, like fluorescence, electrical conductivity, theoretical surface area, low toxicity, and high biocompatibility. In this study, we evaluated genotoxicity (in silico analysis using the functional density theory-FDT), cytotoxicity (human glioblastoma cell line), in vivo pharmacokinetics, in vivo impact on microcirculation and cell internalization assay. It was also radiolabeled with lutetium 177 (177Lu), a beta emitter radioisotope to explore its therapeutic use as nanodrug. Finally, the impact of its disposal in the environment was analyzed using ecotoxicological evaluation. FDT analysis demonstrated that graphene can construct covalent and non-covalent bonds with different nucleobases, and graphene oxide is responsible for generation of reactive oxygen species (ROS), corroborating its genotoxicity. On the other hand, non-cytotoxic effect on glioblastoma cells could be demonstrated. The pharmacokinetics analysis showed high plasmatic concentration and clearance. Topical application of 0.1 and 1 mg/kg of graphene nanoparticles on the hamster skinfold preparation did not show inflammatory effect. The cell internalization assay showed that 1-hour post contact with cells, graphene can cross the plasmatic membrane and accumulate in the cytoplasm. Radio labeling with 177Lu is possible and its use as therapeutic nanosystem is viable. Finally, the ecotoxicity analysis showed that A. silina exposed to graphene showed pronounced uptake and absorption in the nauplii gut and formation of ROS. The data obtained showed that although being formed exclusively of carbon and carbon-oxygen, graphene and graphene oxide respectively generate somewhat contradictory results and more studies should be performed to certify the safety use of this nanoplatform.

scholarly journals Sequence Determinants in Gammaretroviral Env Cytoplasmic Tails Dictate Virus-Specific Pseudotyping Compatibility

2019 ◽  
Vol 93 (11) ◽  
Author(s):  
Yul Eum Song ◽  
Grace Y. Olinger ◽  
Sanath Kumar Janaka ◽  
Marc C. Johnson
Keyword(s):  
Viral Vectors ◽  
Leukemia Virus ◽  
Target Cells ◽  
Gag Protein ◽  
Factors Affecting ◽  
Gene Therapies ◽  
Viral Glycoproteins ◽  
Cytoplasmic Tails ◽  
Specific Manner ◽  
Hiv 1

ABSTRACTViruses can incorporate foreign glycoproteins to form infectious particles through a process known as pseudotyping. However, not all glycoproteins are compatible with all viruses. Despite the fact that viral pseudotyping is widely used, what makes a virus/glycoprotein pair compatible is poorly understood. To study this, we chose to analyze a gammaretroviral glycoprotein (Env) whose compatibility with different viruses could be modulated through small changes in its cytoplasmic tail (CT). One form of this glycoprotein is compatible with murine leukemia virus (MLV) particles but incompatible with human immunodeficiency virus type 1 (HIV-1) particles, while the second is compatible with HIV-1 particles but not with MLV particles. To decipher the factors affecting virus-specific Env incompatibility, we characterized Env incorporation, maturation, cell-to-cell fusogenicity, and virus-to-cell fusogenicity of each Env. The HIV-1 particle incompatibility correlated with less efficient cleavage of the R peptide by HIV-1 protease. However, the MLV particle incompatibility was more nuanced. MLV incompatibility appeared to be caused by lack of incorporation into particles, yet incorporation could be restored by further truncating the CT or by using a chimeric MLV Gag protein containing the HIV-1 MA without fully restoring infectivity. The MLV particle incompatibility appeared to be caused in part by fusogenic repression in MLV particles through an unknown mechanism. This study demonstrates that the Env CT can dictate functionality of Env within particles in a virus-specific manner.IMPORTANCEViruses utilize viral glycoproteins to efficiently enter target cells during infection. How viruses acquire viral glycoproteins has been studied to understand the pathogenesis of viruses and develop safer and more efficient viral vectors for gene therapies. The CTs of viral glycoproteins have been shown to regulate various stages of glycoprotein biogenesis, but a gap still remains in understanding the molecular mechanism of glycoprotein acquisition and functionality regarding the CT. Here, we studied the mechanism of how specific mutations in the CT of a gammaretroviral envelope glycoprotein distinctly affect infectivity of two different viruses. Different mutations caused failure of glycoproteins to function in a virus-specific manner due to distinct fusion defects, suggesting that there are virus-specific characteristics affecting glycoprotein functionality.

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