New Applications of Lipid and Polymer-Based Nanoparticles for Nucleic Acids Delivery

Nucleic acids represent a promising lead for engineering the immune system. However, naked DNA, mRNA, siRNA, and other nucleic acids are prone to enzymatic degradation and face challenges crossing the cell membrane. Therefore, increasing research has been recently focused on developing novel delivery systems that are able to overcome these drawbacks. Particular attention has been drawn to designing lipid and polymer-based nanoparticles that protect nucleic acids and ensure their targeted delivery, controlled release, and enhanced cellular uptake. In this respect, this review aims to present the recent advances in the field, highlighting the possibility of using these nanosystems for therapeutic and prophylactic purposes towards combatting a broad range of infectious, chronic, and genetic disorders.

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

Current Pharmaceutical Design ◽

10.2174/1381612823666171109112307 ◽

2018 ◽

Vol 24 (1) ◽

pp. 62-77 ◽

Cited By ~ 13

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.

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Silencing Antibiotic Resistance with Antisense Oligonucleotides

Biomedicines ◽

10.3390/biomedicines9040416 ◽

2021 ◽

Vol 9 (4) ◽

pp. 416

Author(s):

Saumya Jani ◽

Maria Soledad Ramirez ◽

Marcelo E. Tolmasky

Keyword(s):

Antibiotic Resistance ◽

Nucleic Acids ◽

Antisense Oligonucleotides ◽

Bacterial Infections ◽

Genetic Disorders ◽

Antibiotic Resistance Genes ◽

Short Review ◽

Rnase H ◽

Biological Processes ◽

Locked Nucleic Acids

Antisense technologies consist of the utilization of oligonucleotides or oligonucleotide analogs to interfere with undesirable biological processes, commonly through inhibition of expression of selected genes. This field holds a lot of promise for the treatment of a very diverse group of diseases including viral and bacterial infections, genetic disorders, and cancer. To date, drugs approved for utilization in clinics or in clinical trials target diseases other than bacterial infections. Although several groups and companies are working on different strategies, the application of antisense technologies to prokaryotes still lags with respect to those that target other human diseases. In those cases where the focus is on bacterial pathogens, a subset of the research is dedicated to produce antisense compounds that silence or reduce expression of antibiotic resistance genes. Therefore, these compounds will be adjuvants administered with the antibiotic to which they reduce resistance levels. A varied group of oligonucleotide analogs like phosphorothioate or phosphorodiamidate morpholino residues, as well as peptide nucleic acids, locked nucleic acids and bridge nucleic acids, the latter two in gapmer configuration, have been utilized to reduce resistance levels. The major mechanisms of inhibition include eliciting cleavage of the target mRNA by the host’s RNase H or RNase P, and steric hindrance. The different approaches targeting resistance to β-lactams include carbapenems, aminoglycosides, chloramphenicol, macrolides, and fluoroquinolones. The purpose of this short review is to summarize the attempts to develop antisense compounds that inhibit expression of resistance to antibiotics.

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Surface chemistry modification of silica nanoparticles alters the activation of monocytes

Therapeutic Delivery ◽

10.4155/tde-2021-0006 ◽

2021 ◽

Author(s):

Romina Mitarotonda ◽

Martín Saraceno ◽

Marcos Todone ◽

Exequiel Giorgi ◽

Emilio L Malchiodi ◽

...

Keyword(s):

Flow Cytometry ◽

Immune System ◽

Cell Membrane ◽

Cell Activation ◽

Membrane Damage ◽

Living Cells ◽

Cell Membrane Damage ◽

Study Materials ◽

Therapeutic Molecules ◽

Pro Inflammatory Cytokines

Aim: Nanoparticles (NPs) interaction with immune system is a growing topic of study. Materials & methods: Bare and amine grafted silica NPs effects on monocytes/macrophages cells were analyzed by flow cytometry, MTT test and LIVE/DEAD® viability/cytotoxicity assay. Results: Bare silica NPs inhibited proliferation and induced monocyte/macrophages activation (increasing CD40/CD80 expression besides pro-inflammatory cytokines and nitrite secretion). Furthermore, silica NPs increased cell membrane damage and reduced the number of living cells. In contrast, amine grafted silica NPs did not alter these parameters. Conclusion: Cell activation properties of bare silica NPs could be hindered after grafting with amine moieties. This strategy is useful to tune the immune system stimulation by NPs or to design NPs suitable to transport therapeutic molecules.

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Immunogenetics of the Ocular Anterior Segment: Lessons from Inherited Disorders

Journal of Ophthalmology ◽

10.1155/2021/6691291 ◽

2021 ◽

Vol 2021 ◽

pp. 1-19

Author(s):

Jasmine Y. Serpen ◽

Stephen T. Armenti ◽

Lev Prasov

Keyword(s):

Immune System ◽

Lupus Erythematosus ◽

Genetic Disorders ◽

Anterior Segment ◽

Adaptive Immune System ◽

Mendelian Inheritance ◽

Ocular Involvement ◽

Inherited Disorders ◽

Molecular Features ◽

Organ Systems

Autoimmune and autoinflammatory diseases cause morbidity in multiple organ systems including the ocular anterior segment. Genetic disorders of the innate and adaptive immune system present an avenue to study more common inflammatory disorders and host-pathogen interactions. Many of these Mendelian disorders have ophthalmic manifestations. In this review, we highlight the ophthalmic and molecular features of disorders of the innate immune system. A comprehensive literature review was performed using PubMed and the Online Mendelian Inheritance in Man databases spanning 1973–2020 with a focus on three specific categories of genetic disorders: RIG-I-like receptors and downstream signaling, inflammasomes, and RNA processing disorders. Tissue expression, clinical associations, and animal and functional studies were reviewed for each of these genes. These genes have broad roles in cellular physiology and may be implicated in more common conditions with interferon upregulation including systemic lupus erythematosus and type 1 diabetes. This review contributes to our understanding of rare inherited conditions with ocular involvement and has implications for further characterizing the effect of perturbations in integral molecular pathways.

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Mesoporous Silica Nanoparticles Based Antigens and Nucleic Acids Delivery: A Review

Asian Journal of Pharmaceutical Research and Development ◽

10.22270/ajprd.v8i2.686 ◽

1970 ◽

Vol 8 (2) ◽

pp. 50-57

Author(s):

Jemal Dilebo

Keyword(s):

Mesoporous Silica ◽

Nucleic Acids ◽

Silica Nanoparticles ◽

Mesoporous Silica Nanoparticles ◽

Mesoporous Structure ◽

Nucleic Acid Delivery ◽

Hollow Core ◽

Small Molecule Drugs ◽

Cell Accumulation ◽

Nucleic Acids Delivery

Mesoporous silica nanoparticles (MSN) have been explored for the delivery of small molecule drugs, antigens, and nucleic acids because of their large surface area, pore volume, amenability of their surface for functionalization, stable mesoporous structure, and biocompatibility. Biomoecules loading capacitites, release and target cell accumulation efficiencies have been improved for both antigen and nucleic acid delivery by the synthesis of large-pore MSN, dendritic MSN, hollow-core MSN, and multifunctional MSN. This article overview the major advances in the use of MSN for delivery of antigens and therapeutic nucleic acids such as DNA, siRNA, and miRNA aimed for treatment of various diseases.

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