Biomaterials, Journal Year: 2024, Volume and Issue: 314, P. 122853 - 122853
Published: Sept. 27, 2024
Language: Английский
Frontiers in Cellular and Infection Microbiology, Journal Year: 2025, Volume and Issue: 14
Published: Jan. 20, 2025
Messenger RNA (mRNA) vaccines offer an adaptable and scalable platform for cancer immunotherapy, requiring optimal design to elicit a robust targeted immune response. Recent advancements in bioinformatics artificial intelligence (AI) have significantly enhanced the design, prediction, optimization of mRNA vaccines. This paper reviews technologies that streamline vaccine development, from genomic sequencing lipid nanoparticle (LNP) formulation. We discuss how accurate predictions neoantigen structures guide sequences effectively target cells. Furthermore, we examine AI-driven approaches optimize mRNA-LNP formulations, enhancing delivery stability. These technological innovations not only improve but also enhance pharmacokinetics pharmacodynamics, offering promising avenues personalized immunotherapy.
Language: Английский
Citations
8
Vaccines, Journal Year: 2024, Volume and Issue: 12(10), P. 1148 - 1148
Published: Oct. 8, 2024
The advent of lipid nanoparticles (LNPs) as a delivery platform for mRNA therapeutics has revolutionized the biomedical field, particularly in treating infectious diseases, cancer, genetic disorders, and metabolic diseases. Recent Advances Therapeutic LNPs: LNPs, composed ionizable lipids, phospholipids, cholesterol, polyethylene glycol (PEG) facilitate efficient cellular uptake cytosolic release while mitigating degradation by nucleases. However, synthetic entities, LNPs face challenges that alter their therapeutic efficacy safety concerns. Toxicity/Reactogenicity/Immunogenicity: This review provides comprehensive overview latest advancements LNP research, focusing on preclinical assessments encompassing toxicity, reactogenicity, immunogenicity. Summary Outlook: Additionally, it outlines potential strategies addressing these offers insights into future research directions enhancing application therapeutics.
Language: Английский
Citations
17
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16
Published: March 4, 2025
mRNA vaccines utilize single-stranded linear DNA as a template for in vitro transcription. The is introduced into the cytoplasm via corresponding delivery system to express target protein, which then performs its relevant biological function. are beneficial various fields, including cancer vaccines, infectious disease protein replacement therapy, and treatment of rare diseases. They offer advantages such simple manufacturing process, quick development cycle, ease industrialization. Additionally, afford flexibility adjusting antigen designs combining sequences multiple variants, thereby addressing issue frequent mutations pathogenic microorganisms. This paper aims provide an extensive review global current research status with focus on immunogenicity, classification, design, vector development, stability, biomedical application. Moreover, study highlights challenges offers insights future directions development.
Language: Английский
Citations
1
Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)
Published: Aug. 31, 2024
Abstract Malignant tumors remain a primary cause of human mortality. Among the various treatment modalities for neoplasms, tumor vaccines have consistently shown efficacy and promising potential. These offer advantages such as specificity, safety, tolerability, with mRNA representing platforms. By introducing exogenous mRNAs encoding antigens into somatic cells subsequently synthesizing through gene expression systems, can effectively induce immune responses. Katalin Karikó Drew Weissman were awarded 2023 Nobel Prize in Physiology or Medicine their great contributions to vaccine research. Compared traditional vaccines, several advantages, including rapid preparation, reduced contamination, nonintegrability, high biodegradability. Tumor-targeted therapy is an innovative modality that enables precise targeting cells, minimizes damage normal tissues, safe at doses, demonstrates efficacy. Currently, targeted has become important option malignant tumors. The application tumor-targeted expanding, numerous clinical trials underway. We systematically outline delivery mechanism by which anti-tumor responses, describe current research applications therapy, forecast future development trends therapy.
Language: Английский
Citations
8
Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)
Published: Nov. 14, 2024
RNA therapeutics, such as mRNA, siRNA, and CRISPR–Cas9, present exciting avenues for treating diverse diseases. However, their potential is commonly hindered by vulnerability to degradation poor cellular uptake, requiring effective delivery systems. Lipid nanoparticles (LNPs) have emerged a leading choice in vivo delivery, offering protection against degradation, enhanced facilitation of endosomal escape. LNPs encounter numerous challenges targeted vivo, demanding advanced particle engineering, surface functionalization with targeting ligands, profound comprehension the biological milieu which they function. This review explores structural physicochemical characteristics LNPs, in-vivo fate, customization therapeutics. We highlight quality-by-design (QbD) approach beyond liver, focusing on biodistribution, immunogenicity, toxicity. In addition, we explored current strategies associated ensuring repeated-dose efficacy, safety, tissue-specific gene delivery. Furthermore, provide insights into clinical applications various classes diseases finally prospects
Language: Английский
Citations
8
Vaccines, Journal Year: 2025, Volume and Issue: 13(1), P. 65 - 65
Published: Jan. 13, 2025
Background: Although mRNA vaccines encapsulated in lipid nanoparticles (LNPs) have demonstrated a safety profile with minimal serious adverse events clinical trials, there is opportunity to further reduce reactogenicity. The development of naked could improve vaccine tolerability. Naked nucleic acid delivery using the jet injection method may be solution. Methods: In first part study, optimal conditions providing low traumatization and high expression model mRNA-GFP molecule tissues laboratory animals were determined. Then, we used selected protocol immunize BALB/c mice mRNA-RBD encoding SARS-CoV-2 receptor-binding domain (RBD). It was that vaccinated developed level specific antibodies virus-neutralizing activity. also induced strong RBD-specific T-cell response reduced viral load lungs after infection virus. immune immunized spring-loaded injector comparable LNPs. Results: this efficacy an inexpensive, simple, safe evaluated validated. Conclusions: Our findings suggest possible alternative LNPs for delivering against infection.
Language: Английский
Citations
0
Nanomaterials, Journal Year: 2025, Volume and Issue: 15(2), P. 122 - 122
Published: Jan. 16, 2025
Nano-oncologic vaccines represent a groundbreaking approach in the field of cancer immunotherapy, leveraging unique advantages nanotechnology to enhance effectiveness and specificity treatments. These utilize nanoscale carriers deliver tumor-associated antigens immunostimulatory adjuvants, facilitating targeted immune activation promoting robust antitumor responses. By improving antigen presentation localizing within tumor microenvironment, nano-oncologic can significantly increase efficacy particularly when combined with other treatment modalities. This review highlights mechanisms through which operate, their potential overcome existing limitations treatment, ongoing advancements design. Additionally, it discusses delivery approach, such as EPR effects, pH response, ultrasonic magnetic response. The combination therapy effects photothermal therapy, radiotherapy, or checkpoint inhibitors are also discussed. Overall, hold great promise for changing landscape advancing personalized medicine, paving way more effective therapeutic strategies tailored individual patient needs.
Language: Английский
Citations
0
International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown, P. 125374 - 125374
Published: Feb. 1, 2025
Previous studies showed that intradermal delivery of naked plasmid DNA using the needle-free pyro-drive jet injector, Actranza™, significantly enhanced gene expression compared to needle-syringe injections in animals. Here, we targeted intra-articular (IA) tissues, including cartilage rat knee joint. In order accurately deliver solution joint cavity, Actranza prototype attaching a 30G needle as guide was used (30G-Acranza). The injection powers are controllable adjusting amounts ignition powder (IP) and smokeless (SP). Preliminary tests determined an optimal site (5 mm depth from skin surface into anterior cavity with flexed) volume (30 µL). Initial trials 30G-Actranza-25/40 (IP/SP = 25 mg/40 mg) luciferase (pLuc) levels (relative luminescence units, RLU) were approximately 40 times higher than manual syringe 24 h after administration. Additional Green Fluorescent Protein (pGFP) experiments detected fluorescence chondrocytes cruciate ligament fibroblasts. higher-powered 30G-Actranza-35/40 further increased pLuc injections. remained detectable 10 days post-injection, though reduced day one. Speed-controlled indicated speed, reaching saturation at 693 µL/s 30G-Actranza-35/40. Reference data transdermal favored proximal tissues over IA sites. conclusion, needle-equipped effectively transfects like cartilage, synovium, ligaments, tendons potential applications for encapsulated such tumors, broadening prospects therapy, editing, regenerative medicine.
Language: Английский
Citations
0
The Cancer Journal, Journal Year: 2025, Volume and Issue: 31(2)
Published: March 1, 2025
mRNA vaccines consist of antigen-encoding mRNA, which produces the antigenic protein upon translation. Coupling antigen production with innate immune activation can generate a potent, antigen-specific T-cell response. Clinical reports have demonstrated ability to elicit an anticancer response against various tumor types. Here, we discuss strategies enhance potency vaccines. We provide overview existing knowledge regarding and trafficking mechanisms share optimization boost mRNA-mediated production. In addition, address methods target dendritic cells lymph nodes, key initiators Finally, review for enhancing using adjuvants compatible offer unique advantages that be utilized oncology applications. However, significant work is needed understand their underlying develop technologies improve effectiveness.
Language: Английский
Citations
0
Applied Sciences, Journal Year: 2025, Volume and Issue: 15(8), P. 4428 - 4428
Published: April 17, 2025
Messenger RNA (mRNA) vaccines have exhibited promising potential for infectious disease prevention. Although various delivery methods been explored, the use of electroporation (EP) naked mRNA has received relatively less attention. In this study, we used mouse models to investigate whether vaccine via intramuscular EP (IM-EP) elicits a protective immune response against lethal viral infection. To achieve this, injected C57BL/6 mice with encoding SARS-CoV-2 IM-EP and evaluated resulting responses. IM-EP-mediated induced robust humoral cellular responses, characterized by elevated receptor-binding domain (RBD)-specific IgG antibodies, enhanced IFN-γ production CD8+ T cells, upregulated cytokine expression in muscle lymph nodes. Using K18-hACE2 model, revealed that effectively protected from Overall, our findings suggest can be an effective strategy preventing diseases.
Language: Английский
Citations
0