Molecular Therapy, Год журнала: 2024, Номер unknown
Опубликована: Сен. 1, 2024
Язык: Английский
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(13), С. 7333 - 7333
Опубликована: Июль 4, 2024
Clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology has revolutionized the field of gene therapy as it enabled precise genome editing with unprecedented accuracy and efficiency, paving way for clinical applications to treat otherwise incurable genetic disorders. Typically, requires delivery multiple components target cells that, depending on platform used, may include messenger RNA (mRNA), complexes, DNA fragments. For purposes, these have be efficiently delivered into transplantable cells, such primary T lymphocytes or hematopoietic stem progenitor that are typically sensitive exogenous substances. This challenge limited broad applicability those strategies which efficient methods available. Electroporation-based methodologies been generally applied applications, but procedure-associated toxicity represented a major burden. With advent novel less disruptive deliver cargo is now possible safely editing, thus expanding strategies. In this review, we describe different systems available components, including viral non-viral systems, highlighting their advantages, limitations, recent applications. Recent improvements achieve cell specificity represent critical development enable in vivo targeting future will certainly play pivotal role field.
Язык: Английский
Процитировано
20
Frontiers in Medicine, Год журнала: 2025, Номер 11
Опубликована: Янв. 13, 2025
Gene therapy has long been a cornerstone in the treatment of rare diseases and genetic disorders, offering targeted solutions to conditions once considered untreatable. As field advances, its transformative potential is now expanding into oncology, where personalized therapies address immune-related complexities cancer. This review highlights innovative therapeutic strategies, including gene replacement, silencing, oncolytic virotherapy, CAR-T cell therapy, CRISPR-Cas9 editing, with focus on their application both hematologic malignancies solid tumors. CRISPR-Cas9, revolutionary tool precision medicine, enables precise editing cancer-driving mutations, enhancing immune responses disrupting tumor growth mechanisms. Additionally, emerging approaches target ferroptosis—a regulated, iron-dependent form death—offering new possibilities for selectively inducing death resistant cancers. Despite significant breakthroughs, challenges such as heterogeneity, evasion, immunosuppressive microenvironment (TME) remain. To overcome these barriers, novel like dual-targeting, armored cells, combination checkpoint inhibitors ferroptosis inducers are being explored. rise allogeneic “off-the-shelf” offers scalable more accessible options. The regulatory landscape evolving accommodate advancements, frameworks RMAT (Regenerative Medicine Advanced Therapy) U.S. ATMP (Advanced Therapy Medicinal Products) Europe fast-tracking approval therapies. However, ethical considerations surrounding CRISPR-based editing—such off-target effects, germline ensuring equitable access—remain at forefront, requiring ongoing oversight. Advances non-viral delivery systems, lipid nanoparticles (LNPs) exosomes, improving safety efficacy By integrating innovations addressing concerns, poised revolutionize cancer treatment, providing durable, effective,
Язык: Английский
Процитировано
3
International Journal of Nanomedicine, Год журнала: 2025, Номер Volume 20, С. 25 - 52
Опубликована: Янв. 1, 2025
Abstract: The effective clinical translation of messenger RNA (mRNA), small interfering (siRNA), and microRNA (miRNA) for therapeutic purposes hinges on the development efficient delivery systems. Key challenges include their susceptibility to degradation, limited cellular uptake, inefficient intracellular release. Polymeric drug conjugates (PDCs) offer a promising solution, combining benefits polymeric carriers agents targeted treatment. This comprehensive review explores nucleic acid therapeutics, focusing conjugates. It investigates how these address obstacles, enhance systemic circulation, reduce immunogenicity, provide controlled release, improving safety profiles. delves into conjugation strategies, preparation methods, various classes PDCs, as well strategic design, highlighting role in delivery. Applications PDCs treating diseases such cancer, immune disorders, fibrosis are also discussed. Despite significant advancements, adoption persist. concludes with insights future directions this transformative technology, underscoring potential advance acid-based therapies combat infectious significantly. Keywords: polymer conjugates,
Язык: Английский
Процитировано
1
Circulation Research, Год журнала: 2025, Номер unknown
Опубликована: Март 17, 2025
BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy type 5 (ARVC5) is the most aggressive of ARVC, caused by a fully penetrant missense mutation (p.S358L) in TMEM43 (transmembrane protein 43). Pathologically, disease characterized dilation cardiac chambers and fibrofatty replacement myocardium, which results heart failure sudden death. Current therapeutic options are limited, no specific therapies targeting primary cause have been proposed. METHODS: We investigated whether overexpression wild-type (WT) could overcome detrimental effects mutant form. used transgenic mouse models overexpressing either WT or (S358L) to generate double line both forms protein. In addition, we explored if systemic delivery codon-optimized self-complementary adeno-associated virus bearing WT-TMEM43 improve progression assessed ECG echocardiography. RESULTS: Double mice showed delayed ARVC5 onset, improved contraction, reduced abnormalities compared with expressing S358L-TMEM43. cardiomyocyte death myocardial fibrosis were reduced, an overall increase survival. Finally, demonstrated that single administration carrying prevents dysfunction induced CONCLUSIONS: Overexpression improves pathological phenotype model ARVC5. Adeno-associated virus-mediated offers promising therapy for patients suffering from this highly lethal disease. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT05885412, NCT06109181, NCT06228924.
Язык: Английский
Процитировано
1
The Journal of Microbiology, Год журнала: 2024, Номер 62(7), С. 491 - 509
Опубликована: Июль 1, 2024
Язык: Английский
Процитировано
7
Viruses, Год журнала: 2024, Номер 16(7), С. 1094 - 1094
Опубликована: Июль 8, 2024
Adenoviruses are non-enveloped DNA viruses that cause a wide range of symptoms, from mild infections to life-threatening diseases in broad hosts. Due the unique characteristics these viruses, they have also become vehicle for gene-transfer and cancer therapeutic instruments. Adenovirus vectors can be used gene therapy by modifying wild-type render them replication-defective. This makes it possible swap out particular viral genes segments carry employ resultant vector as means delivering specified tissues. In this review, we outline progressive development adenovirus vectors, exploring their characteristics, genetic modifications, uses clinical preclinical settings. A significant emphasis is placed on crucial role advancing therapy, immunotherapy, latest breakthroughs vaccine various diseases.
Язык: Английский
Процитировано
6
Laboratory Animal Research, Год журнала: 2024, Номер 40(1)
Опубликована: Апрель 22, 2024
Abstract Scientific progress heavily relies on rigorous research, adherence to scientific standards, and transparent reporting. Animal models play a crucial role in advancing biomedical especially the field of gene therapy. are vital tools preclinical allowing scientists predict outcomes understand complex biological processes. The selection appropriate animal is critical, considering factors such as physiological pathophysiological similarities, availability, ethical considerations. continue be indispensable therapy research. Advancements genetic engineering model have improved fidelity relevance these models. As research progresses, careful consideration reporting will contribute development effective therapies for various disorders diseases. This comprehensive review explores use studies approved products up September 2023. study encompasses 47 products, with focus trials. analysis serves valuable reference researchers field, aiding suitable their investigations.
Язык: Английский
Процитировано
5
Biological Procedures Online, Год журнала: 2024, Номер 26(1)
Опубликована: Май 27, 2024
Abstract Exosomes are increasingly recognized as important mediators of intercellular communication in cancer biology. can be derived from cells well cellular components tumor microenvironment. After secretion, the exosomes carrying a wide range bioactive cargos ingested by local or distant recipient cells. The released act through variety mechanisms to elicit multiple biological effects and impact most if not all hallmarks cancer. Moreover, owing their excellent biocompatibility capability being easily engineered modified, currently exploited promising platform for targeted therapy. In this review, we first summarize current knowledge roles risk etiology, initiation progression cancer, underlying molecular mechanisms. aptamer-modified exosome therapy is then briefly introduced. We also discuss future directions emerging biology perspective
Язык: Английский
Процитировано
5
Advanced Materials Technologies, Год журнала: 2025, Номер unknown
Опубликована: Март 3, 2025
Abstract Genetic modification ought to be regarded as a complementary technology that effectively enhances the efficacy of bone rehealing and substitution. Recently, molecular regeneration paths have been uncovered rapid advancement in gene therapy has led heightened interest genetic engineering. Biomaterial scaffold‐mediated offers template for tissue development cell infiltration. Gene‐activated platforms offer an efficient approach precisely delivering genes promote safe effective manner. Moreover, these pathways ability temporarily regulate excessive expression therapeutic genes, resulting localized synthesis regulatory factors at levels are biologically significant. Therefore, application various nucleic acid‐based scaffolds including long noncoding RNAs, short interfering microRNAs, coding mRNAs, plasmids, viral vectors, aptamers, editing tools comprehensively discussed repair regeneration. The bibliography reveals collagen, calcium/phosphate‐based composites, chitosan common scaffolds. Recombinant viruses, miRNAs, siRNAs most prevalent engineering methods. Research findings suggest integration elements biomaterials will revolutionize Tremendous innovations bring such engineered from benches clinics, very soon.
Язык: Английский
Процитировано
0
Journal of Chromatography A, Год журнала: 2024, Номер 1732, С. 465226 - 465226
Опубликована: Авг. 2, 2024
Язык: Английский
Процитировано
4