Recent Advances and Prospects in RNA Drug Development

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(22), С. 12284 - 12284

Опубликована: Ноя. 15, 2024

RNA therapeutics have undergone remarkable evolution since their inception in the late 1970s, revolutionizing medicine by offering new possibilities for treating previously intractable diseases. The field encompasses various modalities, including antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), microRNAs (miRNAs), and messenger (mRNAs), each with unique mechanisms applications. foundation was laid 1978 discovery that synthetic could inhibit viral replication, followed pivotal developments such as interference's 1998. COVID-19 pandemic marked a crucial turning point, demonstrating potential of mRNA vaccines accelerating interest RNA-based approaches. However, significant challenges remain, stability issues, delivery to target tissues, off-target effects, immunogenicity concerns. Recent advancements chemical modifications, systems, integration AI technologies are addressing these challenges. has seen notable successes, approved treatments spinal muscular atrophy hereditary transthyretin-mediated amyloidosis. Looking ahead, show promise personalized approaches, particularly genetic disorders cancer. continued this field, driven technological innovations deeper understanding biology, suggests transformative impact on future medical treatments. purpose review is provide comprehensive overview evolution, current state, prospects therapeutics.

Язык: Английский

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Nebulization of RNA-Loaded Micelle-Embedded Polyplexes as a Potential Treatment of Idiopathic Pulmonary Fibrosis

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown

Опубликована: Фев. 12, 2025

Biodegradable poly(β-amino) esters (PBAEs) have been a focus of interest for delivering therapeutic siRNA several years. While no approved therapies are on the market yet, our study aims to advance PBAE-based treatments currently "undruggable" diseases. The PBAEs used in this based recently reported step-growth copolymerization, which results polymers with unique balance lipophilicity and positive charge, thereby showcasing diverse properties. Upon incubation siRNA, these form structure topology, we classify as subtype classical polyplex, termed "micelle-embedded polyplexes" (mPolyplexes). impact different nebulizers physicochemical performance nanoparticles was investigated, it found that various mPolyplexes can be nebulized using vibrating-mesh without loss gene silencing activity nor change properties, setting them apart from other such marketed LNPs. Finally, their application tested ex vivo human precision-cut lung slices patients fibrosis. mediated 52% matrix metalloprotease 7 (MMP7) downstream effect collagen I (Col I) 33% downregulation determined via qPCR.

Язык: Английский

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Chitosan-based self-healing thermosensitive hydrogel loaded with siHMGB1 for treatment of rheumatoid arthritis via macrophage repolarization

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 282, С. 137102 - 137102

Опубликована: Окт. 31, 2024

Язык: Английский

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The Interplay of Endosomal Escape and RNA Release from Polymeric Nanoparticles

Langmuir, Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

Ribonucleic acid (RNA) nanocarriers, specifically lipid nanoparticles and polymeric nanoparticles, enable RNA transfection both in vitro vivo; however, only a small percentage of endocytosed by cell is delivered to the cytosolic machinery, minimizing its effect. nanocarriers face two major obstacles after endocytosis: endosomal escape release. Overcoming simultaneously challenging because usually achieved using high positive charge disrupt membrane. However, this typically also inhibits release anionic strongly bound nanocarrier electrostatic interactions. Many address one over other despite growing body evidence demonstrating that are crucial for transfection. In review, we survey various strategies have been employed accomplish with focus on nanomaterials. We first consider requirements must achieve delivery including protection from degradation, cellular internalization, escape, then discuss current polymers used examine achieving Finally, review stimuli-responsive While continues be challenge efficient transfection, many new innovations materials elucidated promising strategies.

Язык: Английский

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Novel Baeyer–Villiger Oxidation of Nucleosides Applied to the Large-Scale Synthesis of MeMOP: A Key Amidite in the GalXC Platform

Organic Process Research & Development, Год журнала: 2025, Номер unknown

Опубликована: Март 27, 2025

Язык: Английский

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The next frontier in drug discovery: Unveiling the pharmacological potential of proximity inducers

Elsevier eBooks, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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ncRNAs as Key Regulators in Gastric Cancer: From Molecular Subtyping to Therapeutic Targets

Annals of Surgical Oncology, Год журнала: 2025, Номер unknown

Опубликована: Май 13, 2025

Язык: Английский

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Hepatocyte targeting via the asialoglycoprotein receptor

RSC Medicinal Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Дек. 2, 2024

The asialoglycoprotein receptor (ASGPR) plays a crucial role in delivering therapeutics to hepatocytes. From nucleic acids LYTACs and drugs, we explore the current state-of-the-art strategies for hepatocyte targeting via ASGPR.

Язык: Английский

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Amphiphilic Dynamic Covalent Polymer Vectors of siRNA

Chemical Science, Год журнала: 2024, Номер unknown

Опубликована: Дек. 30, 2024

Hydrophobization of peptide-based dynamic covalent polymer vectors boosts their siRNA delivery performances.

Язык: Английский

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Oligonucleotide Therapies for Facioscapulohumeral Muscular Dystrophy: Current Preclinical Landscape

Опубликована: Июль 22, 2024

Facioscapulohumeral muscular dystrophy (FSHD) is an inherited myopathy, characterized by progressive and asymmetric muscle atrophy, primarily affecting muscles of the face, shoulder girdle, upper arms before lower extremities with age greater disease severity. FSHD a disabling condition, patients may also present various extramuscular symptoms. caused aberrant expression double homeobox 4 (DUX4) in adult skeletal muscle, arising from compromised epigenetic repression D4Z4 array. DUX4 encodes protein, transcription factor that activates myotoxic gene programs to produce pathology. Therefore, sequence-specific oligonucleotides aimed at reducing levels compelling therapeutic approach, one has received considerable research interest over last decade. This review aims describe current preclinical landscape oligonucleotide therapies for FSHD. includes outlining mechanism action each therapy summarizing results obtained regarding their efficacy cellular and/or murine models. The scope this limited oligonucleotide-based inhibit gene, mRNA, or protein way does not involve editing.

Язык: Английский

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