Design and Delivery of Therapeutic siRNAs: Application to MERS-Coronavirus

2018 ◽  
Vol 24 (1) ◽  
pp. 62-77 ◽  
Author(s):  
Sayed Sartaj Sohrab ◽  
Sherif Aly El-Kafrawy ◽  
Zeenat Mirza ◽  
Mohammad Amjad Kamal ◽  
Esam Ibraheem Azhar
Keyword(s):  
Enzymatic Degradation ◽  
Polymeric Nanoparticles ◽  
Genetic Disorders ◽  
Inorganic Nanoparticles ◽  
Innovative Technology ◽  
Viral Diseases ◽  
Viral Gene ◽  
Efficient Delivery ◽  
Disease Therapy ◽  
Target Sites

Background: The MERS-CoV is a novel human coronavirus causing respiratory syndrome since April 2012. The replication of MERS-CoV is mediated by ORF 1ab and viral gene activity can be modulated by RNAi approach. The inhibition of virus replication has been documented in cell culture against multiple viruses by RNAi approach. Currently, very few siRNA against MERS-CoV have been computationally designed and published. Methods: In this review, we have discussed the computational designing and delivery of potential siRNAs. Potential siRNA can be designed to silence a desired gene by considering many factors like target site, specificity, length and nucleotide content of siRNA, removal of potential off-target sites, toxicity and immunogenic responses. The efficient delivery of siRNAs into targeted cells faces many challenges like enzymatic degradation and quick clearance through renal system. The siRNA can be delivered using transfection, electroporation and viral gene transfer. Currently, siRNAs delivery has been improved by using advanced nanotechnology like lipid nanoparticles, inorganic nanoparticles and polymeric nanoparticles. Conclusion: The efficacy of siRNA-based therapeutics has been used not only against many viral diseases but also against non-viral diseases, cancer, dominant genetic disorders, and autoimmune disease. This innovative technology has attracted researchers, academia and pharmaceuticals industries towards designing and development of highly effective and targeted disease therapy. By using this technology, effective and potential siRNAs can be designed, delivered and their efficacy with toxic effects and immunogenic responses can be tested against MERS-CoV.

Strategies for Conjugation of Biomolecules to Nanoparticles as Tumor Targeting Agents

2019 ◽  
Vol 25 (37) ◽  
pp. 3917-3926
Author(s):  
Sajjad Molavipordanjani ◽  
Seyed Jalal Hosseinimehr
Keyword(s):  
Drug Delivery ◽  
Iron Oxide ◽  
Medical Imaging ◽  
Cancer Diagnosis ◽  
Carbon Nanoparticles ◽  
Tumor Targeting ◽  
Polymeric Nanoparticles ◽  
Inorganic Nanoparticles ◽  
Active Targeting ◽  
Cancer Diagnosis And Therapy

Combination of nanotechnology, biochemistry, chemistry and biotechnology provides the opportunity to design unique nanoparticles for tumor targeting, drug delivery, medical imaging and biosensing. Nanoparticles conjugated with biomolecules such as antibodies, peptides, vitamins and aptamer can resolve current challenges including low accumulation, internalization and retention at the target site in cancer diagnosis and therapy through active targeting. In this review, we focus on different strategies for conjugation of biomolecules to nanoparticles such as inorganic nanoparticles (iron oxide, gold, silica and carbon nanoparticles), liposomes, lipid and polymeric nanoparticles and their application in tumor targeting.

scholarly journals Modulation of Macrophages M1/M2 Polarization Using Carbohydrate-Functionalized Polymeric Nanoparticles

Polymers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 88
Author(s):  
Raquel G. D. Andrade ◽  
Bruno Reis ◽  
Benjamin Costas ◽  
Sofia A. Costa Lima ◽  
Salette Reis
Keyword(s):  
Inflammatory Responses ◽  
Polymeric Nanoparticles ◽  
Interaction Mechanism ◽  
Mannose Receptor ◽  
The Body ◽  
Receptor Expression ◽  
Production Methods ◽  
Polymeric Nanocarriers ◽  
Efficient Delivery

Exploiting surface endocytosis receptors using carbohydrate-conjugated nanocarriers brings outstanding approaches to an efficient delivery towards a specific target. Macrophages are cells of innate immunity found throughout the body. Plasticity of macrophages is evidenced by alterations in phenotypic polarization in response to stimuli, and is associated with changes in effector molecules, receptor expression, and cytokine profile. M1-polarized macrophages are involved in pro-inflammatory responses while M2 macrophages are capable of anti-inflammatory response and tissue repair. Modulation of macrophages’ activation state is an effective approach for several disease therapies, mediated by carbohydrate-coated nanocarriers. In this review, polymeric nanocarriers targeting macrophages are described in terms of production methods and conjugation strategies, highlighting the role of mannose receptor in the polarization of macrophages, and targeting approaches for infectious diseases, cancer immunotherapy, and prevention. Translation of this nanomedicine approach still requires further elucidation of the interaction mechanism between nanocarriers and macrophages towards clinical applications.

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 Distribution of polymeric nanoparticles in the eye: implications in ocular disease therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Sean Swetledge ◽  
Jangwook P. Jung ◽  
Renee Carter ◽  
Cristina Sabliov
Keyword(s):  
Polymeric Nanoparticles ◽  
Drug Stability ◽  
Administration Route ◽  
Ocular Diseases ◽  
Ocular Penetration ◽  
Disease Therapy ◽  
Tissue Targeting ◽  
Administration Method ◽  
Potential Impact ◽  
Specific Tissue

Abstract Advantages of polymeric nanoparticles as drug delivery systems include controlled release, enhanced drug stability and bioavailability, and specific tissue targeting. Nanoparticle properties such as hydrophobicity, size, and charge, mucoadhesion, and surface ligands, as well as administration route and suspension media affect their ability to overcome ocular barriers and distribute in the eye, and must be carefully designed for specific target tissues and ocular diseases. This review seeks to discuss the available literature on the biodistribution of polymeric nanoparticles and discuss the effects of nanoparticle composition and administration method on their ocular penetration, distribution, elimination, toxicity, and efficacy, with potential impact on clinical applications.

scholarly journals PLA-PEG Nanoparticles Improve the Anti-Inflammatory Effect of Rosiglitazone on Macrophages by Enhancing Drug Uptake Compared to Free Rosiglitazone

Materials ◽  
2018 ◽  
Vol 11 (10) ◽  
pp. 1845 ◽  
Author(s):  
Giovanna Giacalone ◽  
Nicolas Tsapis ◽  
Ludivine Mousnier ◽  
Hélène Chacun ◽  
Elias Fattal
Keyword(s):  
Polymeric Nanoparticles ◽  
Heart Diseases ◽  
The United States ◽  
Drug Uptake ◽  
Dependent Manner ◽  
Raw264.7 Macrophages ◽  
Efficient Delivery ◽  
Anti Inflammatory ◽  
Atherosclerosis Treatment ◽  
Inflammatory Effect

Among cardiovascular diseases, atherosclerosis remains the first cause of death in the United States of America and Europe, as it leads to myocardial infarction or stroke. The high prevalence of heart diseases is due to the difficulty in diagnosing atherosclerosis, since it can develop for decades before symptoms occur, and to the complexity of the treatment since targets are also important components of the host defenses. The antidiabetics thiazolidinediones, among which is rosiglitazone (RSG), have demonstrated anti-atherosclerotic effect in animal models, and are therefore promising candidates for the improvement of atherosclerosis management. Nevertheless, their administration is hindered by the insurgence of severe side effects. To overcome this limitation, rosiglitazone has been encapsulated into polymeric nanoparticles, which permit efficient delivery to its nuclear target, and selective delivery to the site of action, allowing the reduction of unwanted effects. In the present work, we describe nanoparticle formulation using polylactic acid (PLA) coupled to polyethylene glycol (PEG), their characterization, and their behavior on RAW264.7 macrophages, an important target in atherosclerosis treatment. RSG nanocarriers showed no toxicity on cells at all concentrations tested, an anti-inflammatory effect in a dose-dependent manner, up to 5 times more efficient than the free molecule, and an increased RSG uptake which is consistent with the effect shown. These biodegradable nanoparticles represent a valid tool to be further investigated for the treatment of atherosclerosis.

Nonviral Vehicles for Gene Delivery

Nano LIFE ◽  
2021 ◽  
Vol 11 (02) ◽  
pp. 2130002
Author(s):  
Eric Warga ◽  
Brian Austin-Carter ◽  
Noelle Comolli ◽  
Jacob Elmer
Keyword(s):  
Gene Delivery ◽  
Lower Cost ◽  
Clinical Applications ◽  
Inorganic Nanoparticles ◽  
Nonviral Gene Delivery ◽  
Viral Gene ◽  
Cationic Polymers ◽  
Recent Developments ◽  
Low Efficiency ◽  
Viral Gene Delivery

Nonviral gene delivery (NVGD) is an appealing alternative to viral gene delivery for clinical applications due to its lower cost and increased safety. A variety of promising nonviral vectors are under development, including cationic polymers, lipids, lipid-polymer hybrids (LPHs) and inorganic nanoparticles. However, some NVGD strategies have disadvantages that have limited their adoption, including high toxicity and low efficiency. This review focuses on the most common NVGD vehicles with an emphasis on recent developments in the field.

Polymeric nanoparticles as carrier for targeted and controlled delivery of anticancer agents

2019 ◽  
Vol 10 (8) ◽  
pp. 527-550 ◽  
Author(s):  
Vahid Taghipour-Sabzevar ◽  
Tahere Sharifi ◽  
Mehrdad Moosazadeh Moghaddam
Keyword(s):  
Adverse Effect ◽  
Drug Delivery ◽  
Controlled Release ◽  
Anticancer Agents ◽  
Blood Circulation ◽  
Enzymatic Degradation ◽  
Water Solubility ◽  
Polymeric Nanoparticles ◽  
Controlled Delivery ◽  
Drug Adverse Effect

In recent decades, many novel methods by using nanoparticles (NPs) have been investigated for diagnosis, drug delivery and treatment of cancer. Accordingly, the potential of NPs as carriers is very significant for the delivery of anticancer drugs, because cancer treatment with NPs has led to the improvement of some of the drug delivery limitations such as low blood circulation time and bioavailability, lack of water solubility, drug adverse effect. In addition, the NPs protect drugs against enzymatic degradation and can lead to the targeted and/or controlled release of the drug. The present review focuses on the potential of NPs that can help the targeted and/or controlled delivery of anticancer agents for cancer therapy.

scholarly journals Functionalized lipid-like nanoparticles for in vivo mRNA delivery and base editing

2020 ◽  
Vol 6 (34) ◽  
pp. eabc2315 ◽  
Author(s):  
Xinfu Zhang ◽  
Weiyu Zhao ◽  
Giang N. Nguyen ◽  
Chengxiang Zhang ◽  
Chunxi Zeng ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Low Dose ◽  
Genetic Disorders ◽  
Base Editing ◽  
Guide Rna ◽  
Efficient Delivery ◽  
Human Factor Viii ◽  
Mrna Therapeutics ◽  
Further Development

Messenger RNA (mRNA) therapeutics have been explored to treat various genetic disorders. Lipid-derived nanomaterials are currently one of the most promising biomaterials that mediate effective mRNA delivery. However, efficiency and safety of this nanomaterial-based mRNA delivery remains a challenge for clinical applications. Here, we constructed a series of lipid-like nanomaterials (LLNs), named functionalized TT derivatives (FTT), for mRNA-based therapeutic applications in vivo. After screenings on the materials, we identified FTT5 as a lead material for efficient delivery of long mRNAs, such as human factor VIII (hFVIII) mRNA (~4.5 kb) for expression of hFVIII protein in hemophilia A mice. Moreover, FTT5 LLNs demonstrated high percentage of base editing on PCSK9 in vivo at a low dose of base editor mRNA (~5.5 kb) and single guide RNA. Consequently, FTT nanomaterials merit further development for mRNA-based therapy.

scholarly journals The State of the Art of Theranostic Nanomaterials for Lung, Breast, and Prostate Cancers

Nanomaterials ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 2579
Author(s):  
Lucas F. Freitas ◽  
Aryel H. Ferreira ◽  
Velaphi C. Thipe ◽  
Gustavo H. C. Varca ◽  
Caroline S. A. Lima ◽  
...  
Keyword(s):  
State Of The Art ◽  
Polymeric Nanoparticles ◽  
Drug Dose ◽  
The State ◽  
Inorganic Nanoparticles ◽  
Diagnostic Tools ◽  
Optimal Size ◽  
Breast And Prostate Cancer ◽  
Prostate Cancers ◽  
Cancer Tissues

The synthesis and engineering of nanomaterials offer more robust systems for the treatment of cancer, with technologies that combine therapy with imaging diagnostic tools in the so-called nanotheranostics. Among the most studied systems, there are quantum dots, liposomes, polymeric nanoparticles, inorganic nanoparticles, magnetic nanoparticles, dendrimers, and gold nanoparticles. Most of the advantages of nanomaterials over the classic anticancer therapies come from their optimal size, which prevents the elimination by the kidneys and enhances their permeation in the tumor due to the abnormal blood vessels present in cancer tissues. Furthermore, the drug delivery and the contrast efficiency for imaging are enhanced, especially due to the increased surface area and the selective accumulation in the desired tissues. This property leads to the reduced drug dose necessary to exert the desired effect and for a longer action within the tumor. Finally, they are made so that there is no degradation into toxic byproducts and have a lower immune response triggering. In this article, we intend to review and discuss the state-of-the-art regarding the use of nanomaterials as therapeutic and diagnostic tools for lung, breast, and prostate cancer, as they are among the most prevalent worldwide.

scholarly journals CRISPR as a Versatile Technology for Gene Activation and Genome Editing

2018 ◽  
Vol 4 ◽  
pp. 5
Author(s):  
Habib Rezanejadbardeji ◽  
Bahareh Behroozi-Asl ◽  
Raheleh Amirkhah
Keyword(s):  
Immune System ◽  
Therapeutic Potential ◽  
Genetic Disorders ◽  
Gene Activation ◽  
Adaptive Immune System ◽  
Stem Cell Differentiation ◽  
Zinc Finger Nucleases ◽  
Viral Gene ◽  
Transcription Activator ◽  
Adaptive Immune

CRISPR/Cas system, a microbial adaptive immune system, has rapidly transformed the ways researchers can interrogate the genome. CRISPR has many advantages over traditional methods such as Transcription activator-like effector nucleases (TALEN) and Zinc-finger nucleases (ZFN). Since CRISPR discovery as an adaptive immune system used by bacterial against viruses, it has been repurposed to help in many different genome-related studies such as gene knocking in and out, gene expression upregulation and downregulation. Also CRISPR holds vast therapeutic potential for the management of genetic disorders by straight modifying disease-causing mutations. Although the Cas9 protein has been revealed to attach and cleave DNA at off-target sites, the field of Cas9 specificity is quickly progressing, with marked modifying in guide RNA choice, protein and guide engineering, innovative enzymes, and off-target recognition methods. In current review we mostly focus on CRISPR unique ability in gene activation/ upregulation, which has wide applications in different aspects such as gene studies, stem cell differentiation, and trans-differentiation. Compared to other gene activation methods such as viral gene overexpression, TALEN and ZFN, CRISPR offers many benefits such as easy designing and high precision.

Sign in / Sign up

Export Citation Format

Share Document