Interdisciplinary cancer research, Journal Year: 2024, Volume and Issue: unknown
Published: Jan. 1, 2024
Language: Английский
Bioanalysis, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 16
Published: Feb. 3, 2025
Undruggable targets account for roughly 85% of human disease-related and represent a category therapeutic that are difficult to tackle with traditional methods, but their considerable clinical importance. These generally defined by planar functional interfaces the absence efficient ligand-binding pockets, making them unattainable conventional pharmaceutical strategies. The advent oligonucleotide-based proteolysis-targeting chimeras (PROTACs) has instilled renewed optimism in addressing these challenges. PROTACs facilitate targeted degradation undruggable entities, including transcription factors (TFs) RNA-binding proteins (RBPs), via proteasome-dependent mechanisms, thereby presenting novel approaches diseases linked targets. This review offers an in-depth examination recent progress integration PROTAC technology oligonucleotides target traditionally proteins, emphasizing design principles mechanisms action innovative PROTACs.
Language: Английский
Citations
1
Published: Jan. 1, 2025
Language: Английский
Citations
0
Toxics, Journal Year: 2025, Volume and Issue: 13(3), P. 178 - 178
Published: Feb. 28, 2025
Billions of people are exposed to fine particulate matter (PM2.5) levels above the USEPA’s annual standard 9 μg/m3. Common emission sources anthropogenic, producing complex aerosolized toxins. Ultrafine (UFPM) and industrial nanoparticles (NPs) have major detrimental effects on brain, but USA does not measure UFPM a routine basis. This review focuses development progression common neurodegenerative diseases, as diagnosed through neuropathology, among young residents in Metropolitan Mexico City (MMC). MMC is one most polluted megacities world, with population 22 million residents, many whom unaware brain caused by their atmosphere. Fatal diseases (such Alzheimer’s Parkinson’s) that begin childhood populations living air environments preventable. We conclude UFPM/NPs capable disrupting neural homeostasis give rise relentless processes throughout entire life highly MMC. The paradigm reaching old age neurodegeneration no longer supported. Neurodegenerative changes start early pediatric ages irreversible. It time invest preventive medicine.
Language: Английский
Citations
0
Physical Sciences Reviews, Journal Year: 2025, Volume and Issue: unknown
Published: March 4, 2025
Abstract This chapter highlights challenges and advancements in the production of lipid-based nanoparticles (LNPs) their application nucleic acid-based therapies. Recently, mRNA-based vaccines for COVID-19 immunization revealed that use acids is a promising strategy to develop treatments at high therapeutic efficiency reduced side effects. In this context, LNPs emerged as favourable vehicles delivery (like mRNA DNA), due biocompatibility, bioavailability, versatility. The four main components employed produce loaded with are: cationic or ionizable lipids, helper cholesterol, PEGylated lipids. Several conventional techniques have been proposed over years kind nanoparticles. However, they show many drawbacks hinder direct vesicles characterized by nanometric size, encapsulation active pharmaceutical ingredient, prolonged stability. Processes assisted supercritical fluids (in particular, CO 2 ) can represent sustainable interesting alternative without using post-processing steps solvent removal size reduction are time-consuming procedures, lead large loss acids, negatively influence general productivity process.
Language: Английский
Citations
0
Coordination Chemistry Reviews, Journal Year: 2025, Volume and Issue: 538, P. 216718 - 216718
Published: April 22, 2025
Language: Английский
Citations
0
Journal of Controlled Release, Journal Year: 2025, Volume and Issue: unknown, P. 113774 - 113774
Published: April 1, 2025
Language: Английский
Citations
0
Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)
Published: May 2, 2025
Abstract The quality and fidelity of DNA vectors used in genetic medicine gene therapy either as starting material for manufacturing or therapeutic ingredients play a critical role determining ultimate clinical success. Ministring (msDNA), is novel minivector that linear covalently-closed (LCC) double-stranded molecule devoid immunogenic bacterial sequences (e.g., origin replication, antibiotic resistant cassette). Similar to traditional plasmids, msDNA manufactured vivo E. coli therefore benefits from the scalability -based systems ~ 1000-fold enhanced conferred by mismatch repair (MMR) mechanism. In this paper, we address improved stability msDNA. We show due torsion-free structure, more stable chemical mechanical stress than conventional plasmid DNA. Moreover, demonstrate lyophilization can further improve long-term msDNA, reducing need cold chain storage. Therefore, propose be new paradigm offering with lower immunogenicity, reduced risk insertional mutagenesis, higher stability.
Language: Английский
Citations
0
Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown
Published: May 7, 2025
Ionizable lipid serves as the key functional component in nanoparticles (LNPs) for efficient mRNA delivery. This study aims to systematically evaluate clinically approved ionizable DLin-MC3-DMA and SM102-based LNPs ocular delivery, with a comprehensive assessment of their physicochemical characteristics, delivery efficiency, biodistribution patterns within microenvironment. Enhanced green fluorescence protein or Luc encoding mRNA-loaded were formulated using microfluidic mixing technology characterized by dynamic light scattering, ζ-potential measurements, cryogenic transmission electron microscopy imaging. The two LNP systems different cationic lipids demonstrated distinct capabilities vitro transfection intraocular following intravitreal administration. Notably, SM102-LNPs exhibited superior performance compared MC3-LNPs, significantly higher efficiency retinal cells vitro, more expression minimal systemic distribution vivo. Safety that administration maintained excellent long-term biocompatibility throughout five-month period. establishes promising platform therapeutics.
Language: Английский
Citations
0
Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: unknown, P. 115460 - 115460
Published: Oct. 1, 2024
Language: Английский
Citations
0
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13540 - 13540
Published: Dec. 18, 2024
Gene transfection is a fundamental technique in the fields of biological research and therapeutic innovation. Due to their biocompatibility membrane-mimetic properties, lipid vectors serve as essential tools transfection. The successful delivery genetic material into cytoplasm contingent upon fusion vector cellular membranes, which enables hydrophilic polynucleic acids traverse hydrophobic barriers two intervening membranes. This review examines critical role membrane lipofection efficiency, with particular focus on molecular mechanisms that govern lipoplex–membrane interactions. analysis will examine key challenges inherent process, from achieving initial proximity facilitating final content release through remodeling. In contrast viral vectors, utilize specialized proteins, necessitate strategic formulation environmental optimization enhance fusogenicity. discusses recent advances design fusion-promoting strategies, emphasizing potential improve gene yield. It highlights importance understanding for developing next-generation systems emphasizes need continued advance lipid-mediated technology.
Language: Английский
Citations
0