Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Ноя. 14, 2024

Abstract In the last decade, messenger ribonucleic acid (mRNA)-based drugs have gained great interest in both immunotherapy and non-immunogenic applications. This surge can be largely attributed to demonstration of distinct advantages offered by various mRNA molecules, alongside rapid advancements nucleic delivery systems. It is noteworthy that immunogenicity presents a double-edged sword. context immunotherapy, extra supplementation adjuvant generally required for induction robust immune responses. Conversely, non-immunotherapeutic scenarios, activation unwanted considering host tolerability high expression demand mRNA-encoded functional proteins. Herein, mainly focused on linear non-replicating mRNA, we overview preclinical clinical progress prospects medicines encompassing vaccines other therapeutics. We also highlight importance focusing host-specific variations, including age, gender, pathological condition, concurrent medication individual patient, maximized efficacy safety upon administration. Furthermore, deliberate potential challenges may encounter realm disease treatment, current endeavors improvement, as well application future advancements. Overall, this review aims present comprehensive understanding mRNA-based therapies while illuminating prospective development drugs.

Язык: Английский

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What is the role of microbial biotechnology and genetic engineering in medicine?

MicrobiologyOpen, Год журнала: 2024, Номер 13(2)

Опубликована: Март 31, 2024

Abstract Microbial products are essential for developing various therapeutic agents, including antibiotics, anticancer drugs, vaccines, and enzymes. Genetic engineering techniques, functional genomics, synthetic biology unlock previously uncharacterized natural products. This review highlights major advances in microbial biotechnology, focusing on gene‐based technologies medical applications.

Язык: Английский

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A Modular Self‐Assembling and Self‐Adjuvanting Multiepitope Peptide Nanoparticle Vaccine Platform to Improve the Efficacy and Immunogenicity of BCG

Small, Год журнала: 2025, Номер unknown

Опубликована: Янв. 5, 2025

Abstract After more than a century since its initial development, Bacille Calmette‐Guérin (BCG) remains the only licensed vaccine against tuberculosis (TB). Subunit boosters are considered viable strategy to enhance BCG efficacy, which often wanes in adolescence. While many studies on booster subunit vaccines have concentrated recombinant proteins, here we developed novel modular peptide‐based platform that is flexible, cold‐chain independent and customizable diverse circumstances populations. Each individual peptide building block consists of linear arrangement comprising 15‐leucine self‐assembly inducer moiety, Mycobacterium (Mtb) target epitope an human leukocyte antigen E (HLA‐E) binding with each moiety separated by triple lysine spacer. The blocks, any combination, able form multiepitope nanoparticle. Six Mtb epitopes were selected produce self‐assembling self‐adjuvating TB nano‐vaccine candidate PNx6. In vivo vaccination‐challenge experiments demonstrated subcutaneous boost parenteral immunization PNx6 significantly enhanced immunogenicity improved protective efficacy murine model 5‐fold. This study presents evidence purely amphiphilic peptides self‐assemble into nanoparticles appropriate size morphology for vaccination great potential multitude other diseases.

Язык: Английский

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Specific immune response to M. tuberculosis and ability to in vitro control mycobacterial replication are not impaired in subjects with immune-mediated inflammatory disease and tuberculosis infection

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 13, 2025

Background Subjects with immune-mediated inflammatory diseases (IMID), such as rheumatoid arthritis, tuberculosis infection (TBI), have a high probability of progressing to disease (TB). We aim characterize the impact IMID on immune response M. (Mtb) in patients TBI and TB disease. Methods enrolled without IMID. Peripheral blood mononuclear cells (PBMCs) were stimulated Mtb-derived epitopes (MTB300). By flow-cytometry, we identified Mtb-specific CD4 + T cytokine-producing or CD25 CD134 cells. Memory activation status assessed by evaluating: CD153, HLA-DR, CD45RA, CD27. Mycobacterial growth inhibition assay (MGIA) was used evaluate ability PBMCs inhibit mycobacteria growth. A long-term stimulation detect memory response. Results The therapy did not affect magnitude Mtb-antigen number responders. TBI-IMID showed cytokine profile like patients. Mtb characterized an effector central phenotype groups. This allowed increased IFN-γ production after 6 days MTB300-stimulation. HLA-DR expression associated TB, whereas CD153 status. Finally, had MGIA Conclusion condition does key aspects Mtb, response, profile, contain replication. immunological characterization fragile population is fundamental understanding correlation between protection

Язык: Английский

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RNA vaccines: The dawn of a new age for tuberculosis?

Human Vaccines & Immunotherapeutics, Год журнала: 2025, Номер 21(1)

Опубликована: Фев. 27, 2025

Since 2019, there has been a growing focus on mRNA vaccines for infectious disease prevention, particularly following the emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). offer advantages such as rapid production and ability to induce robust cellular antibody responses, which are essential combating infections that require cell-mediated immunity, including Tuberculosis (TB). This review explores recent progress in TB addresses several key areas: (1) urgent need new vaccines; (2) current advancements vaccine development, challenges technology; (3) design characteristics (4) immunological mechanisms (5) manufacturing processes (6) safety regulatory considerations. interdisciplinary aims provide insights researchers working address critical questions development.

Язык: Английский

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Mannose-modified erythrocyte membrane-coated Chuanmingshen violaceum polysaccharide PLGA nanoparticles to improve immune responses in mice

International Immunopharmacology, Год журнала: 2025, Номер 152, С. 114450 - 114450

Опубликована: Март 12, 2025

Язык: Английский

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The Plasma Membrane P-Type ATPase CtpA Is Required for Mycobacterium tuberculosis Virulence in Copper-Activated Macrophages in a Mouse Model of Progressive Tuberculosis

Biomedicines, Год журнала: 2025, Номер 13(2), С. 439 - 439

Опубликована: Фев. 11, 2025

Background/Objective: Finding new targets to attenuate Mycobacterium tuberculosis (Mtb) is key in the development of TB vaccines. In this context, plasma membrane P-type ATPases are relevant for mycobacterial homeostasis and virulence. work, we investigate role copper-transporting ATPase CtpA Mtb Methods: The impact deletion on Mtb's capacity overcome redox stress proliferate mouse alveolar macrophages (MH-S) was evaluated, as well its effect immunogenicity. Moreover, influence pathogenicity a (BALB/c) model progressive examined. Results: We found that MH-S cells infected with wild-type (MtbH37Rv) or mutant strain (MtbH37RvΔctpA) showed no difference bacterial load. However, same under copper activation (50 µM CuSO4) impaired replication strain. Furthermore, MtbΔctpA an inability control reactive oxygen species (ROS) induced by PMA addition during infection. These results, together high expression Nox2 mRNA observed Mtb∆ctpA at 3 6 days post-infection, suggest potential overcoming infection conditions. addition, MtbΔctpA-infected BALB/c mice survived longer significantly lower lung loads tissue damage their lungs than MtbH37Rv-infected mice. Conclusions: This suggests involved virulence it may be target attenuation.

Язык: Английский

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Inhaled aerosol viral-vectored vaccines against tuberculosis

Current Opinion in Virology, Год журнала: 2024, Номер 66, С. 101408 - 101408

Опубликована: Апрель 3, 2024

Bacille Calmette-Guérin (BCG) remains the sole licensed vaccine against tuberculosis (TB), despite its variable efficacy in protecting pulmonary TB. The development of effective TB vaccines faces significant challenges, marked by absence validated correlates protection and predictive animal models. Strategic approaches to enhance augment BCG include utilising prime-boost strategies with viral-vectored exploring innovative delivery techniques, such as mucosal administration. Viral vectors offer numerous advantages, including capacity accommodate genes encoding extensive antigenic fragments induction robust immune responses. Aerosol aligns route Mycobacterium infection holds potential protective immunity. Aerosolised overcome anti-vector immunity, facilitating repeated aerosol deliveries.

Язык: Английский

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Historical Examination of Tuberculosis; From Ancient Affliction to Modern Challenges

Journal of Infection and Public Health, Год журнала: 2025, Номер 18(3), С. 102649 - 102649

Опубликована: Янв. 5, 2025

Tuberculosis (TB), white plague, many other definitions is an ancient deadly infection that humans dealt with after creation. The first hypothesis refers to 150 million years ago about the appearance of TB in Jurassic era before human creation, but documents show 9000 for society. In 1882, Robert Koch was able identify and describe best possible agent TB. After discovery TB's [Mycobacterium tuberculosis], progress made diagnosis treatment rapidly, invasive operations such as surgery were replaced drug chemical compounds hired so effective resistance occurrence. this review authors done their tries all aspects [identification, epidemics, diagnostics, development, etc.] history from records present condition give insight into future ending 2030 2050.

Язык: Английский

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Personalized nanovaccines for treating solid cancer metastases

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Ноя. 28, 2024

Cancer vaccines have garnered attention as a potential treatment for cancer metastases. Nevertheless, the clinical response rate to remains < 30%. Nanoparticles stabilize and improve antigen recognition presentation, resulting in high tumor penetration or accumulation, effective co-distribution of drugs secondary lymphatic system, adaptable adjuvant administration. Such vaccine-like nanomedicines ability eradicate primary tumors well prevent eliminate This review examines state-of-the-art nanocarriers developed deliver metastases, including synthetic, semi-biogenic, biogenic nanosystems. Moreover, it highlights physical pharmacological properties that enhance their anti-metastasis efficiency. also addresses combination nanovaccines with immunotherapy target various steps metastatic cascade, drawing insights from preclinical studies. The concludes critical analysis challenges frameworks linked translation nanovaccines.

Язык: Английский

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