Nano Today, Год журнала: 2024, Номер 59, С. 102517 - 102517
Опубликована: Окт. 10, 2024
Язык: Английский
Vaccines, Год журнала: 2024, Номер 12(7), С. 727 - 727
Опубликована: Июнь 29, 2024
With its unique properties and potential applications, nanoparticle-based delivery platforms for messenger RNA (mRNA) vaccines have gained significant attention in recent years. Nanoparticles the advantages of enhancing immunogenicity, targeting delivery, improving stability, providing a new solution drug vaccine delivery. In some clinical studies, variety nanoparticle been gradually applied to wide range applications. Current research priorities are exploring various types nanoparticles as systems enhance stability immunogenicity. Lipid (LNPs) shown promising preclinical studies on efficient antigens immune cells. Moreover, lipid other nucleic acids, especially mRNA systems, vast development. this review, we present with an emphasis vehicles. We describe several novel vaccines, such lipid-, polymer-, protein-based nanoparticles. addition, provide overview anti-tumor immunity nanovaccines against different tumors cancer immunotherapy. Finally, outline future perspectives remaining challenges technology vaccines.
Язык: Английский
Процитировано
14
Nano Letters, Год журнала: 2024, Номер 24(30), С. 9368 - 9376
Опубликована: Июль 16, 2024
Development of mRNA therapeutics necessitates targeted delivery technology, while the clinically advanced lipid nanoparticles face difficulty for extrahepatic delivery. Herein, we design highly branched poly(β-amino ester)s (HPAEs) efficacious organ-selective through tailoring their chemical compositions and topological structures. Using an "A2+B3+C2" Michael addition platform, a combinatorial library 219 HPAEs with varied backbone structures, terminal groups, branching degrees are synthesized. The structures provide enhanced serum resistance significantly higher expression in vivo. amine determine organ-selectivity following systemic administration: morpholine facilitates liver targeting, ethylenediamine favors spleen delivery, methylpentane enables to liver, spleen, lungs simultaneously. This study represents comprehensive exploration structure–activity relationship governing both efficiency by HPAEs, suggesting promising candidates treating various organ-related diseases.
Язык: Английский
Процитировано
10
Advanced Materials, Год журнала: 2025, Номер unknown
Опубликована: Янв. 2, 2025
Abstract Cancer immunotherapy, specifically Chimeric Antigen Receptor (CAR)‐T cell therapy, represents a significant breakthrough in treating cancers. Despite its success hematological cancers, CAR‐T exhibits limited efficacy solid tumors, which account for more than 90% of all Solid tumors commonly present unique challenges, including antigen heterogeneity and complex tumor microenvironment (TME). To address these, efforts are being made through improvements CAR design the development advanced validation platforms. While is limited, some types, such as neuroblastoma gastrointestinal have shown responsiveness to therapy recent clinical trials. In this review, it first examined both experimental computational strategies, protein engineering coupled with machine learning, developed enhance T specificity. The challenges methods associated delivery vivo reprogramming discussed. It also explored advancements engineered organoid systems, emerging high‐fidelity vitro models that closely mimic human TME serve platform discovery. Collectively, these innovative strategies offer potential revolutionize next generation ultimately paving way effective treatments tumors.
Язык: Английский
Процитировано
1
Nature Reviews Methods Primers, Год журнала: 2024, Номер 4(1)
Опубликована: Окт. 10, 2024
Язык: Английский
Процитировано
4
BMC Genomics, Год журнала: 2025, Номер 26(1)
Опубликована: Фев. 4, 2025
The 5′ UTR is critical for mRNA stability and translation efficiency in therapeutics. We developed UTR-Insight, a model integrating pretrained language with CNN-Transformer architecture, explaining 89.1% of the mean ribosome load (MRL) variation random UTRs 82.8% endogenous UTRs, surpassing existing models. Using we performed high-throughput silico screening hundreds thousands from primates, mice, viruses. screened sequences increased protein expression by up to 319% compared human α-globin UTR, UTR-Insight-designed achieved even greater levels than high-performing UTRs.
Язык: Английский
Процитировано
0
Immunological Investigations, Год журнала: 2025, Номер unknown, С. 1 - 19
Опубликована: Фев. 21, 2025
IL-7 is a cytokine that plays critical role in the development and proliferation of many different immune cells. notably important for proper activity T cells B Additionally, function natural killer dendritic Because this innate biological activity, has gained traction as potential immunotherapy multiple applications. We conducted comprehensive literature review to explore physiological current applications harnessing biology therapeutic. also investigated ways which being engineered enhance its therapeutic potential. Notably, demonstrated efficacy adoptive cell therapy models vaccine adjuvant. The been used treatment sepsis other chronic infections. To further efficacy, by fusing antibody fragments or bioactive targeting molecules. These therapeutics seek improve cytokine's pharmacokinetic immunological properties reduce off-target effects. immunotherapies largely remain at preclinical stage, but there growing interest IL-7's increasing opportunities engineer molecule future clinical translation.
Язык: Английский
Процитировано
0
Scientific Reports, Год журнала: 2025, Номер 15(1)
Опубликована: Апрель 18, 2025
This study evaluated the ability of ELISpot to identify potential immuno-modulatory drug therapies in sepsis. was performed ex vivo on whole blood from septic patients and healthy controls. Innate adaptive immunity were by production TNF-α IFN-γ, respectively. Drug efficacy determined their effects modulate both number cytokine-producing cells amount cytokine produced per cell. The corticosteroid dexamethasone for its down IFN-γ production. TLR7/8 agonist resiquimod (R848) T cell stimulants IL-7 anti-PD-1 mAb tested enhance immunity. LPS increased total 1,549% 1,829%, Conversely, diminished responses or 75% 61%, IL-7, but not markedly subjects (121%) (82%). Dexamethasone also reduced anti-CD3/CD28 stimulated 69%; while ameliorated dexamethasone-induced suppression. significantly enhanced lymphocyte function over 90% patients. can reveal host immune response patterns drugs selectively down- up-regulate patient Furthermore, detect effect specific independently regulate innate could enable precision-based
Язык: Английский
Процитировано
0
Advanced Materials, Год журнала: 2025, Номер unknown
Опубликована: Апрель 26, 2025
Abstract The clinical progress of tumor nucleotide vaccines is limited due to insufficient recognition and killing cells with low antigen expression by cytotoxic T lymphocytes (CTL). Here, natural cholesterol analogs are screened assemble self‐adjuvant lipid nanoparticles (LNPs) for antigens tagging dendritic (DC) activation. First, a library ginsenosides collected, then according their anti‐tumor immunity. Then, ginsenoside‐Rg3 based‐LNPs loaded (Rg3‐LNPs) identified as the optimal formulation investigating physicochemical biological properties. Finally, Rg3‐LNPs granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) co‐loaded into macroporous hydrogel long‐term immune response. could accumulate both tumors LNs. targeted high glucose transporter‐1 via targeting ligand Rg3, anchored on cell surface, thus promoting CTL cells; can LNs promote DC activation presentation, stimulating Besides, an adjuvant, cooperated GM‐CSF remodel microenvironment, cells. Collectively, this work highlights importance in vaccine has great value immune‐escaping tumors.
Язык: Английский
Процитировано
0
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Авг. 5, 2024
Abstract Messenger RNA (mRNA)-based transient expression of CAR shows optimal safety profiles and provides promising opportunities to address existing challenges viral vector-based CAR-T therapies meet emerging medical needs in noncancerous indications. However, linear mRNAs are intrinsically unstable thus just achieve compromised efficacy. Here, we engineered a permuted intron exon (PIE) platform synthesize scarless circular mRNA (cmRNA) for potent long-lasting cmRNA significantly increased amount duration anti-CD19 on human T cells. cmRNA-based cells elicit superior anti-tumor efficacy over counterparts, demonstrated by parallel lines evidence including vitro specific cell-killing, cytokine release, transcriptomics patterns, vivo tumor elimination survival benefit. We found that efficiently eliminated target provide antitumor These results suggested could be unleashing full potential technologies cell therapies.
Язык: Английский
Процитировано
3
Journal of Biomedical Science, Год журнала: 2024, Номер 31(1)
Опубликована: Сен. 10, 2024
Abstract Realizing the immense clinical potential of mRNA-based drugs will require continued development methods to safely deliver bioactive agents with high efficiency and without triggering side effects. In this regard, lipid nanoparticles have been successfully utilized improve mRNA delivery protect cargo from extracellular degradation. Encapsulation in was an essential factor successful application vaccines, which conclusively demonstrated technology's yield approved medicines. review, we begin by describing current advances modifications, design novel lipids nanoparticle components for drugs. Then, summarize key points pertaining preclinical therapeutics. Finally, cover topics related targeted systems, including endosomal escape targeting immune cells, tumors organs use vaccines new treatment modalities human diseases.
Язык: Английский
Процитировано
3