Oral Administration as an Alternative Route for Sustained-Release Hydrogel-Encapsulated Anti-Caries Gene Vaccine (Preprint) DOI Creative Commons
Hu Li, Xiaoyan Guan, Min Li

et al.

Published: Dec. 6, 2024

UNSTRUCTURED Streptococcus mutans (S. mutans) is the primary pathogenic bacterium causing dental caries, and protein antigen (SpaP) of its P region glucan-binding (Gbp) with domain (GBD) exhibit promising immunogenicity. They have been separately utilized in development anti-caries vaccines, but their effectiveness needs enhancement. To improve immune response address challenges acidic gastrointestinal environment, such as degradation, mucosal barriers, inefficient cellular absorption by cells, rapid enzymatic degradation this study aims to create an innovative vaccine using a temperature-sensitive sustained-release hydrogel carrier evaluate vaccine's both vitro vivo. In study, we successfully connected antigens recombinant SpaP from S. GbpA. Using hydrogel, PLGA-PEG-PLGA, carrier, pVAX1-SPG was prepared. Initially, effect observed vitro. Subsequently, rabbits were immunized orally injection conduct general safety testing. improved release vitro, maintaining efficacy for longer duration. rabbits, it induced elevation SpaP-specific serum IgG saliva IgA antibodies. Moreover, administered stronger antibodies than route. No abnormalities detected various indicators. The hydrogel-encapsulated gene can elicit significantly effective long-term response. oral route proves be more readily accepted safer alternative, holding enormous potential prevention treatment caries.

Language: Английский

The next-generation DNA vaccine platforms and delivery systems: advances, challenges and prospects DOI Creative Commons
Bowen Lu,

Jing Ming Lim,

Boyue Yu

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 1, 2024

Vaccines have proven effective in the treatment and prevention of numerous diseases. However, traditional attenuated inactivated vaccines suffer from certain drawbacks such as complex preparation, limited efficacy, potential risks others. These limitations restrict their widespread use, especially face an increasingly diverse range With ongoing advancements genetic engineering vaccines, DNA emerged a highly promising approach both diseases acquired While several demonstrated substantial success animal models diseases, challenges need to be addressed before application human subjects. The primary obstacle lies absence optimal delivery system, which significantly hampers immunogenicity vaccines. We conduct comprehensive analysis current status by focusing on viral non-viral systems, they play crucial roles exploration novel provide evaluation strengths weaknesses based our critical assessment. Additionally, review summarizes most recent breakthroughs pre-clinical clinical studies, highlighting for further trials this rapidly evolving field.

Language: Английский

Citations

46
Mechanisms and Delivery of tRNA Therapeutics DOI
Cian Ward, Aruun Beharry,

Rasangi Tennakoon

et al.

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(12), P. 7976 - 8008

Published: May 27, 2024

Transfer ribonucleic acid (tRNA) therapeutics will provide personalized and mutation specific medicines to treat human genetic diseases for which no cures currently exist. The tRNAs are a family of adaptor molecules that interpret the nucleic sequences in our genes into amino proteins dictate cell function. Humans encode more than 600 tRNA genes. Interestingly, even healthy individuals contain some mutant make mistakes. Missense suppressor insert wrong proteins, nonsense read through premature stop signals generate full length proteins. Mutations underlie many diseases, including neurodegenerative cancers, diverse rare disorders, result from missense or mutations. Thus, variants can be strategically deployed as therapeutic agents correct defects. We review mechanisms activity, nature window suppression well wild-type supplementation. discuss challenges promises delivering synthetic RNAs gene therapies. Together, novel treatments common humans.

Language: Английский

Citations

6
Delivery vehicle and route of administration influences self-amplifying RNA biodistribution, expression kinetics, and reactogenicity DOI Creative Commons

Nuthan Vikas Bathula,

Josh J. Friesen,

Irafasha C. Casmil

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 374, P. 28 - 38

Published: Aug. 8, 2024

Self-amplifying RNA (saRNA) is a next-generation platform derived from an alphavirus that enables replication in host cytosol, offering promising shift traditional messenger (mRNA) therapies by enabling sustained protein production minimal dosages. The approval of saRNA-based vaccines, such as the ARCT-154 for COVID-19 Japan, underscores its potential diverse therapeutic applications, including vaccine development, cancer immunotherapy, and gene therapy. This study investigates role delivery vehicle administration route on saRNA expression kinetics reactogenicity. Employing ionizable lipid-based nanoparticles (LNPs) polymeric nanoparticles, we administered encoding firefly luciferase to BALB/c mice through six routes (intramuscular (IM), intradermal (ID), intraperitoneal (IP), intranasal (IN), intravenous (IV), subcutaneous (SC)), observed persistent over month. Our findings reveal while LNPs enable broad applicability stability, pABOL (poly (cystamine bisacrylamide-co-4-amino-1-butanol)) formulations significantly amplify via intramuscular delivery. Notably, disparity between biodistribution highlight nuanced interplay routes, vehicles, outcomes. Additionally, our research unveiled distinct profiles inflammatory responses contingent upon chosen formulation route. illuminates intricate dynamics governing delivery, reactogenicity, essential insights optimizing strategies advancing clinical commercial viability technologies.

Language: Английский

Citations

6
The Role of Biological Sex in Pre-Clinical (Mouse) mRNA Vaccine Studies DOI Creative Commons

Burcu Binici,

Zahra Rattray, Avi Schroeder

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(3), P. 282 - 282

Published: March 7, 2024

In this study, we consider the influence of biological sex-specific immune responses on assessment mRNA vaccines in pre-clinical murine studies. Recognising established disparities function attributed to genetic and hormonal differences between individuals different sexes, compared expression mice both sexes after intramuscular injection with incorporated within lipid nanoparticles. Regarding expression, no significant difference protein (luciferase) at site was observed female male following administration; however, found that BALB/c exhibit significantly greater total IgG across concentration range nanoparticles (LNPs) comparison their counterparts. This study not only contributes scientific understanding vaccine evaluation but also emphasizes importance considering sex designs during

Language: Английский

Citations

4
An LNP-mRNA vaccine modulates innate cell trafficking and promotes polyfunctional Th1 CD4+ T cell responses to enhance BCG-induced protective immunity against Mycobacterium tuberculosis DOI Creative Commons

Hannah Lukeman,

Hareth Al-Wassiti, Stewart A. Fabb

et al.

EBioMedicine, Journal Year: 2025, Volume and Issue: 113, P. 105599 - 105599

Published: Feb. 16, 2025

Language: Английский

Citations

0
Current advances and future prospects of cell reprogramming in progeroid syndromes DOI Creative Commons
Lucas Moledo-Nodar,

Víctor Celemín-Capaldi,

Alejandro P. Ugalde

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 19, 2025

Cell reprogramming consists in the reverse process to cell differentiation, making cells lose their identity and age-related characteristics granting an increased potential for proliferation redifferentiation on different lineages. This holds immense treatment of several pathologies, including progeroid syndromes, diseases that recapitulate symptoms seen physiological aging accelerated manner. Among recent advances use context interventions based partial reprogramming, consisting dedifferentiation only up a point which they age related but keep identity, stand out. can be achieved both using forced expression transcription factors or cocktails small molecules regulate biological processes. While all these are promising, syndromes still faces challenges, such as development methods allow efficient delivery vivo fine tuning dose used. Furthermore, approaches should accompanied by treatments targeting original cause disease could proven futile long term.

Language: Английский

Citations

0
Modulation of lipid nanoparticle-formulated plasmid DNA drives innate immune activation promoting adaptive immunity DOI Creative Commons
Nicholas J. Tursi, Sachchidanand Tiwari, Nicole M. Bedanova

et al.

Cell Reports Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 102035 - 102035

Published: March 1, 2025

Language: Английский

Citations

0
Lipid nanoparticle-encapsulated DNA vaccine confers protection against swine and human-origin H1N1 influenza viruses DOI Creative Commons
The Nhu Nguyen, Danh Cong Lai,

Sarah Sillman

et al.

mSphere, Journal Year: 2024, Volume and Issue: 9(8)

Published: Aug. 28, 2024

ABSTRACT In 2009, a novel swine-origin H1N1 virus emerged, causing pandemic. The virus, known as H1N1pdm09, quickly displaced the circulating H1 lineage and became dominant seasonal influenza A subtype infecting humans. Human-to-swine spillovers of H1N1pdm09 have occurred frequently, each occurrence has led to sustained transmission human-origin within swine populations. present study, we developed lipid nanoparticle-based DNA vaccine (LNP-DNA) containing hemagglutinin gene H1N1pdm09. pigs, this LNP-DNA induced robust antibody response after single intramuscular immunization protected pigs against challenge infection with homologous virus. mouse model, T-cell responses mice lethal mouse-adapted These findings demonstrate potential protect both swine- viruses. IMPORTANCE Swine (IAV) is widespread causes significant economic losses industry. Moreover, bidirectional IAV between humans commonly occurs. Once introduced into population, often reassorts endemic IAV, resulting in reassortant Thus, it imperative develop that not only effective strains but also capable preventing spillover IAV. nanoparticle-encapsulated plasmid demonstrates efficacy vaccines are non-infectious non-viable, meeting criteria serve platform for rapidly updating vaccines. Collectively, approach holds great alleviating impact on industry emergence strains.

Language: Английский

Citations

3
New insights for the development of efficient DNA vaccines DOI Creative Commons
Simone Berger, Yanira Zeyn, Ernst Wagner

et al.

Microbial Biotechnology, Journal Year: 2024, Volume and Issue: 17(11)

Published: Nov. 1, 2024

Abstract Despite the great potential of DNA vaccines for a broad range applications, ranging from prevention infections, over treatment autoimmune and allergic diseases to cancer immunotherapies, implementation such therapies clinical is far behind expectations up now. The main reason poor immunogenicity in humans. Consequently, improvement performance vivo required. This mini‐review provides an overview current state various strategies enhance immunogenic vaccines, including (i) optimization construct itself regarding size, nuclear transfer transcriptional regulation; (ii) use appropriate adjuvants; (iii) improved delivery, example, by careful choice administration route, physical methods as electroporation nanomaterials that may allow cell type‐specific targeting. Moreover, combining nanoformulated with other immunotherapies prime‐boost help success treatment.

Language: Английский

Citations

2
Novel Efficient Lipid-Based Delivery Systems Enable a Delayed Uptake and Sustained Expression of mRNA in Human Cells and Mouse Tissues DOI Creative Commons

Artem G. Fedorovskiy,

Denis N. Antropov,

Anton S. Dome

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(5), P. 684 - 684

Published: May 19, 2024

Over the past decade, mRNA-based therapy has displayed significant promise in a wide range of clinical applications. The most striking example leap development mRNA technologies was mass vaccination against COVID-19 during pandemic. emergence large-scale technology and positive experience immunization sparked antiviral anti-cancer vaccines as well therapeutic agents for genetic other diseases. To facilitate delivery, lipid nanoparticles (LNPs) have been successfully employed. However, diverse use approaches requires adaptable LNP delivery systems that can control kinetics uptake expression target cells. Here, we report effective into cultured mammalian cells (HEK293T, HeLa, DC2.4) living mouse muscle tissues by liposomes containing either 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride (2X3) or newly applied 1,30-bis(cholest-5-en-3β-yloxycarbonylamino)-9,13,18,22-tetraaza-3,6,25,28-tetraoxatriacontane (2X7) cationic lipids. Using end-point real-time monitoring Fluc expression, showed these LNPs exhibited an unusually delayed (of over 10 h case 2X7-based system) but had highly efficient prolonged reporter activity Accordingly, both formulations decorated with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG2000) provided luciferase production mice, peaking on day 3 after intramuscular injection. Notably, bioluminescence observed only at site injection caudal thigh muscles, thereby demonstrating local model gene interest. developed hold prophylactic applications, where sustained synthesis defensive proteins is required, open doors to new possibilities therapies.

Language: Английский

Citations

1