Current Understanding and Translational Prospects of Tetrahedral Framework Nucleic Acids

JACS Au, Год журнала: 2025, Номер 5(2), С. 486 - 520

Опубликована: Фев. 10, 2025

Tetrahedral framework nucleic acids (tFNAs) represent a promising advancement in acid nanotechnology due to their unique structural properties, high biocompatibility, and multifaceted biomedical applications. Constructed through one-pot annealing method, four single-stranded DNAs self-assemble into stable, three-dimensional tetrahedral nanostructures with enhanced mechanical robustness physiological stability, resisting enzymatic degradation. Their ability permeate mammalian cells without transfection agents, coupled modifiable surfaces, positions tFNAs as versatile carriers for drug gene delivery systems. The tFNA-based platforms exhibit superior therapeutic efficacy, including antioxidative anti-inflammatory effects, alongside efficient cellular uptake tissue penetration. These features underpin role precision medicine, enabling targeted of diverse agents such synthetic compounds, peptides, acids. Additionally, demonstrate significant potential regenerative immune modulation, antibacterial strategies, oncology. By addressing challenges translational integration, stand poised accelerate the development research clinical applications, fostering novel therapies enhancing outcomes across wide spectrum diseases. This Perspective thoroughly details attributes applications critically evaluates tFNAs' potential, outlining inherent implementation exploring solutions these obstacles.

Язык: Английский

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Natural, modified and conjugated carbohydrates in nucleic acids

Chemical Society Reviews, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

The deep interconnection between nucleic acids and carbohydrates has prompted numerous synthetic campaigns to understand acid etiology, develop orthogonal genetic systems, improve the properties of therapeutic oligonucleotides.

Язык: Английский

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A platform method for simultaneous quantification of lipid and nucleic acid components in lipid nanoparticles

Journal of Chromatography A, Год журнала: 2025, Номер 1746, С. 465788 - 465788

Опубликована: Фев. 17, 2025

Язык: Английский

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Metabolic Stability and Targeted Delivery of Oligonucleotides: Advancing RNA Therapeutics Beyond The Liver

Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 8, 2025

Oligonucleotides have emerged as a formidable new class of nucleic acid therapeutics. Fully modified oligonucleotides exhibit enhanced metabolic stability and display successful clinical applicability for targets formerly considered "undruggable". Accumulating studies show that conjugation to targeting modalities stabilized oligonucleotides, especially small interfering RNAs (siRNAs), has enabled robust delivery intended cells/tissues. However, the major challenge in field been targeted (siRNAs antisense (ASOs)) extrahepatic tissues. In this Perspective, we review chemistry innovations emerging approaches revolutionized oligonucleotide drug discovery development. We explore findings from both academia industry highlight potential indications involving different organs─including skeletal muscles, brain, lungs, skin, heart, adipose tissue, eyes. all, continued advances coupled with conjugation-based or novel administration routes will further advance

Язык: Английский

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What are biopharmaceuticals?

Опубликована: Янв. 10, 2025

Throughout history, biopharmaceuticals have been essential in addressing health crises and enhancing human well-being. With advancements genetic engineering, biotechnology, bioinformatics, the development approval rates of new surged, placing them at forefront pharmaceutical field. Modern manufacturing processes streamlined regulatory pathways further expedited timelines, providing hope for previously untreatable conditions significantly improving patients’ quality life worldwide. However, despite these advancements, ambiguity persists regarding definition due to use varied terms a lack standardized definitions. This article addresses this confusion by proposing clear comprehensive biopharmaceuticals. Additionally, we present reclassification into seven distinct verticals based on their functions. We assert that not only offer superior therapeutic benefits but also contribute environmental sustainability, promoting healthier planet. Thus, aims clarify scope advocate broader adoption pursuit global integrity.

Язык: Английский

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Advances in Duchenne Muscular Dystrophy: Diagnostic Techniques and Dystrophin Domain Insights

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(8), С. 3579 - 3579

Опубликована: Апрель 10, 2025

Abnormalities in X chromosomes, either numerical or structural, cause X-linked disorders, such as Duchenne muscular dystrophy (DMD). Recent molecular and cytogenetic techniques can help identify DMD gene mutations. The accurate diagnosis of is crucial, directly impacting patient treatment management, genetics, the establishment effective prevention strategies. This review provides an overview chromosomal disorders affecting discusses how mutations Dystrophin domains impact detection accuracy. Firstly, efficiency use for genetic disease have, thus, become increasingly important. Secondly, artificial intelligence (AI) will be instrumental developing future therapies by enabling aggregation synthesis extensive heterogeneous datasets, thereby elucidating underlying mechanisms. However, despite advances diagnostic technology, understanding role remains a challenge. Therefore, this aims to synthesize complex information significantly advance it could affect care.

Язык: Английский

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Selective suppression of influenza A/H5N1 virus replication <i>in vitro</i> using nanocomplexes consisting of siRNA and aminopropylsilanol nanoparticles

Journal of microbiology epidemiology immunobiology, Год журнала: 2025, Номер 101(6), С. 794 - 802

Опубликована: Янв. 14, 2025

Relevance. Studies on model systems have confirmed the effectiveness of antisense oligonucleotides, including those that contain photoactive groups, for modification nucleic acids. However, this strategy has not yet found wide application due to lack successful methods intracellular delivery. The development effective preparations capable acting target acids in cells is an urgent task. aim study create nanocomplexes consisting aminopropylsilanol nanoparticles and short interfering RNA (siRNA) their effect by example inhibition influenza A virus replication vitro. Materials methods. MDCK cells, A/chicken/Kurgan/05/2005 (A/H5N1), nanoparticles, native modified siRNA molecules. Results discussion. We prepared unique Si~NH2/siRNA nanocomplexes, which consist molecules, enable cell penetration selective interaction with acids, respectively. antiviral activity proposed been studied infected A/H5N1 virus. It shown double-stranded molecules act interference mechanism, are more efficient inhibiting than corresponding single-stranded fragments. most nanocomplex contained targeted at chosen region mRNA segment 5 viral genome reduced culture a factor 630. non-agglomerated water-soluble low-toxic, delivering into protecting from hydrolysis cellular nucleases. Conclusion. biological created demonstrated highly suppression system.

Язык: Английский

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Opportunities for More Tailored Approaches to Genotoxicity Testing and Carcinogenicity Strategy for Oligonucleotide Therapeutics: Outcome of an Industry Survey

Nucleic Acid Therapeutics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 23, 2025

The Oligonucleotide Nonclinical Working Group (WG) of the European Federation Pharmaceutical Industries and Associations conducted an industry survey to understand current practices regulatory expectations for genotoxicity carcinogenicity assessment oligonucleotide therapeutics (ONTs), along with historical testing results. survey, involving 29 pharmaceutical biotechnology companies, revealed a consistent absence across diverse range classes chemistries, previous observations. Despite lack genotoxicity, companies continue follow standard guidelines, only limited divergence. data support view that well-established ONT modifications can be considered "precedented," in terms negligible genotoxic risk. As such, further new candidates containing precedented is unwarranted, when defined criteria are met. Further, we propose pathway novel chemical achieve status. results also indicate alternative strategies (e.g., single-species testing) accepted by agencies under certain circumstances. Overall, findings underscore need more tailored approach nonclinical safety ONTs, WG proposes development supplementary questions International Council Harmonisation Technical Requirements Pharmaceuticals Human Use S2(R1) guidance reflect this broad experience.

Язык: Английский

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Novel RNA-Based Therapies in the Management of Dyslipidemias

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 1026 - 1026

Опубликована: Янв. 25, 2025

Pharmaceutical advancements and an improved understanding of pathophysiology have enabled innovative therapies for chronic conditions like dyslipidemia. This condition is marked by abnormalities in lipid homeostasis. Nucleic acid therapeutics, including antisense oligonucleotides small interfering RNAs, are novel management strategies that silence genes targeting mRNA. Antisense modify mRNA to inhibit protein production, whereas RNAs induce degradation via the RNA-induced silencing complex (RISC), thus offering promising treatments dyslipidemia atherosclerotic cardiovascular disease. Chemical modifications improve their stability targeting. RNA-based PCSK9, Lp(a), ApoC-III, ANGPTL3 hold transformative potential treating effectively. article discusses latest data from completed ongoing trials on RNA dyslipidemia, inclisiran, pelacarsen, olpasiran, zerlasiran, lepodisiran, volanesorsen, olezarsen, plozasiran, zodasiran, solbinsiran. Each therapy targets specific molecules while also significantly impacting other parameters. The results these indicate improvements risk reduction, with studies expected further refine role agents effective management.

Язык: Английский

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Bioanalytical Assays for Oligonucleotide Therapeutics: Adding Antibody-Based Immunoassays to the Toolbox as an Orthogonal Approach to LC-MS/MS and Ligand Binding Assays

Nucleic Acid Therapeutics, Год журнала: 2025, Номер 35(1), С. 6 - 15

Опубликована: Фев. 1, 2025

Язык: Английский

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