scholarly journals Nanotechnologies in Delivery of DNA and mRNA Vaccines to the Nasal and Pulmonary Mucosa

Nanomaterials ◽  
2022 ◽  
Vol 12 (2) ◽  
pp. 226
Author(s):  
Jie Tang ◽  
Larry Cai ◽  
Chuanfei Xu ◽  
Si Sun ◽  
Yuheng Liu ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Pulmonary Delivery ◽  
Nucleic Acid Delivery ◽  
Mucosal Vaccination ◽  
Biological Barriers ◽  
Airway Mucosa ◽  
Nucleic Acid Vaccines ◽  
Mucosal Site ◽  
Recent Developments

Recent advancements in the field of in vitro transcribed mRNA (IVT-mRNA) vaccination have attracted considerable attention to such vaccination as a cutting-edge technique against infectious diseases including COVID-19 caused by SARS-CoV-2. While numerous pathogens infect the host through the respiratory mucosa, conventional parenterally administered vaccines are unable to induce protective immunity at mucosal surfaces. Mucosal immunization enables the induction of both mucosal and systemic immunity, efficiently removing pathogens from the mucosa before an infection occurs. Although respiratory mucosal vaccination is highly appealing, successful nasal or pulmonary delivery of nucleic acid-based vaccines is challenging because of several physical and biological barriers at the airway mucosal site, such as a variety of protective enzymes and mucociliary clearance, which remove exogenously inhaled substances. Hence, advanced nanotechnologies enabling delivery of DNA and IVT-mRNA to the nasal and pulmonary mucosa are urgently needed. Ideal nanocarriers for nucleic acid vaccines should be able to efficiently load and protect genetic payloads, overcome physical and biological barriers at the airway mucosal site, facilitate transfection in targeted epithelial or antigen-presenting cells, and incorporate adjuvants. In this review, we discuss recent developments in nucleic acid delivery systems that target airway mucosa for vaccination purposes.

scholarly journals Synthetic Histidine-Rich Peptides Inhibit Candida Species and Other Fungi In Vitro: Role of Endocytosis and Treatment Implications

2006 ◽  
Vol 50 (8) ◽  
pp. 2797-2805 ◽  
Author(s):  
Jingsong Zhu ◽  
Paul W. Luther ◽  
Qixin Leng ◽  
A. James Mixson
Keyword(s):  
Nucleic Acid ◽  
Antifungal Activity ◽  
Antifungal Agents ◽  
Fungal Growth ◽  
Nucleic Acid Delivery ◽  
Histatin 5 ◽  
Ph Buffering ◽  
Endosomal Acidification

ABSTRACT A family of histidine-rich peptides, histatins, is secreted by the parotid gland in mammals and exhibits marked inhibitory activity against a number of Candida species. We were particularly interested in the mechanism by which histidine-rich peptides inhibit fungal growth, because our laboratory has synthesized a variety of such peptides for drug and nucleic acid delivery. In contrast to naturally occurring peptides that are linear, peptides made on synthesizers can be varied with respect to their degrees of branching. Using this technology, we explored whether histidine-lysine (HK) polymers of different complexities and degrees of branching affect the growth of several species of Candida. Polymers with higher degrees of branching were progressively more effective against Candida albicans, with the four-branched polymer, H2K4b, most effective. Furthermore, H2K4b accumulated efficiently in C. albicans, which may indicate its ability to transport other antifungal agents intracellularly. Although H2K4b had greater antifungal activity than histatin 5, their mechanisms were similar. Toxicity in C. albicans induced by histatin 5 or branched HK peptides was markedly reduced by 4,4′-diisothiocyanato-stilbene-2,2′-disulfonate, an inhibitor of anion channels. We also determined that bafilomycin A1, an inhibitor of endosomal acidification, significantly decreased the antifungal activity of H2K4b. This suggests that the pH-buffering and subsequent endosomal-disrupting properties of histidine-rich peptides have a role in their antifungal activity. Moreover, the ability of the histidine component of these peptides to disrupt endosomes, which allows their escape from the lysosomal pathway, may explain why these peptides are both effective antifungal agents and nucleic acid delivery carriers.

IMMU-53. STING-ING GLIOBLASTOMA WITH SPHERICAL NUCLEIC ACIDS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi104-vi105
Author(s):  
Akanksha Mahajan ◽  
Lisa Hurley ◽  
Serena Tommasini-Ghelfi ◽  
Corey Dussold ◽  
Alexander Stegh ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
High Surface ◽  
Biological Properties ◽  
Innate Immune ◽  
Limiting Factors ◽  
Nucleic Acid Delivery ◽  
Sting Pathway ◽  
Spherical Nucleic Acids

Abstract The Stimulator of Interferon Genes (STING) pathway represents a major innate immune sensing mechanism for tumor-derived DNA. Modified cyclic dinucleotides (CDNs) that mimic the endogenous STING ligand cGAMP are currently being explored in patients with solid tumors that are amenable to intratumoral delivery. Inadequate bioavailability and insufficient lipophilicity are limiting factors for clinical CDN development, in particular when consideration is given to systemic administration approaches. We have shown that the formulation of oligonucleotides into Spherical Nucleic Acid (SNA) nanostructures, i.e.,the presentation of oligonucleotides at high density on the surface of nanoparticle cores, lead to biochemical and biological properties that are radically different from those of linear oligonucleotides. First-generation brain-penetrant siRNA-based SNAs (NCT03020017, recurrent GBM) have recently completed early clinical trials. Here, we report the development of a STING-agonistic immunotherapy by targeting cGAS, the sensor of cytosolic dsDNA upstream of STING, with SNAs presenting dsDNA at high surface density. The strategy of using SNAs exploits the ability of cGAS to raise STING responses by delivering dsDNA and inducing the catalytic production of endogenous CDNs. SNA nanostructures carrying a 45bp IFN-simulating dsDNA oligonucleotide, the most commonly used and widely characterized cGAS activator, potently activated the cGAS-STING pathway in vitro and in vivo. In a poorly immunogenic and highly aggressive syngeneic mouse glioma model, in which tumours were well-established, only one dose of intranasal treatment with STING-SNAs decelerated tumour growth, improved survival and importantly, was well-tolerated. Our use of SNAs addresses the challenges of nucleic acid delivery to intracranial tumor sites via intranasal route, exploits the binding of dsDNA molecules on the SNA surface to enhance the formation of a dimeric cGAS:DNA complex and establishes cGAS-agonistic SNAs as a novel class of immune-stimulatory modalities for triggering innate immune responses against tumor.

scholarly journals Recent Developments in Peptide-Based Nucleic Acid Delivery

2008 ◽  
Vol 9 (7) ◽  
pp. 1276-1320 ◽  
Author(s):  
Sandra Veldhoen ◽  
Sandra Laufer ◽  
Tobias Restle
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acid Delivery ◽  
Recent Developments

Cationic DOPC-Detergent Conjugates for Safe and Efficient in Vitro and in Vivo Nucleic Acid Delivery

ChemBioChem ◽  
2016 ◽  
Vol 17 (18) ◽  
pp. 1771-1783 ◽  
Author(s):  
Philippe Pierrat ◽  
Anne Casset ◽  
Pascal Didier ◽  
Dimitri Kereselidze ◽  
Marie Lux ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acid Delivery

scholarly journals A Direct Comparison of in Vitro and in Vivo Nucleic Acid Delivery Mediated by Hundreds of Nanoparticles Reveals a Weak Correlation

Nano Letters ◽  
2018 ◽  
Vol 18 (3) ◽  
pp. 2148-2157 ◽  
Author(s):  
Kalina Paunovska ◽  
Cory D. Sago ◽  
Christopher M. Monaco ◽  
William H. Hudson ◽  
Marielena Gamboa Castro ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acid Delivery ◽  
Weak Correlation

scholarly journals Self-assembling asymmetric peptide-dendrimer micelles – a platform for effective and versatile in vitro nucleic acid delivery

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Ganesh R. Kokil ◽  
Rakesh N. Veedu ◽  
Bao Tri Le ◽  
Grant A. Ramm ◽  
Harendra S. Parekh
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acid Delivery ◽  
Self Assembling ◽  
Peptide Dendrimer

scholarly journals Multifunctional Immunoadjuvants for Use in Minimalist Nucleic Acid Vaccines

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 644
Author(s):  
Saed Abbasi ◽  
Satoshi Uchida
Keyword(s):  
Nucleic Acid ◽  
Immune Responses ◽  
Nucleic Acids ◽  
Innate Immune ◽  
Great Promise ◽  
Nucleic Acid Delivery ◽  
Subunit Vaccines ◽  
Adaptive Immune ◽  
Nucleic Acid Vaccines ◽  
And Control

Subunit vaccines based on antigen-encoding nucleic acids have shown great promise for antigen-specific immunization against cancer and infectious diseases. Vaccines require immunostimulatory adjuvants to activate the innate immune system and trigger specific adaptive immune responses. However, the incorporation of immunoadjuvants into nonviral nucleic acid delivery systems often results in fairly complex structures that are difficult to mass-produce and characterize. In recent years, minimalist approaches have emerged to reduce the number of components used in vaccines. In these approaches, delivery materials, such as lipids and polymers, and/or pDNA/mRNA are designed to simultaneously possess several functionalities of immunostimulatory adjuvants. Such multifunctional immunoadjuvants encode antigens, encapsulate nucleic acids, and control their pharmacokinetic or cellular fate. Herein, we review a diverse class of multifunctional immunoadjuvants in nucleic acid subunit vaccines and provide a detailed description of their mechanisms of adjuvanticity and induction of specific immune responses.

Components Simulation of Viral Envelope via Amino Acid Modified Chitosans for Efficient Nucleic Acid Delivery: In Vitro and In Vivo Study

2012 ◽  
Vol 23 (21) ◽  
pp. 2691-2699 ◽  
Author(s):  
Jing Chang ◽  
Xianghui Xu ◽  
Haiping Li ◽  
Yeting Jian ◽  
Gang Wang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Nucleic Acid ◽  
Viral Envelope ◽  
In Vivo Study ◽  
Nucleic Acid Delivery

Aptamer-based modulation of blood coagulation

2011 ◽  
Vol 31 (04) ◽  
pp. 258-263 ◽  
Author(s):  
F. Rohrbach ◽  
B. Pötzsch ◽  
J. Müller ◽  
G. Mayer
Keyword(s):  
Clinical Trials ◽  
Nucleic Acid ◽  
In Vitro Selection ◽  
Three Dimensional ◽  
Selection Procedure ◽  
Anticoagulant Drugs ◽  
Coagulation Proteins ◽  
Recent Developments ◽  
Target Molecules

SummaryNucleic acid based aptamers are singlestranded oligonucleotide ligands isolated from random libraries by an in-vitro selection procedure. Through the formation of unique three-dimensional structures, aptamers are able to selectively interact with a variety of target molecules and are therefore also promising candidates for the development of anticoagulant drugs. While thrombin represents the most prominent enzymatic target in this field, also aptamers directed against other coagulation proteins and proteases have been identified with some currently being tested in clinical trials.In this review, we summarize recent developments in the design and evaluation of aptamers for anticoagulant therapy and research.

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