Journal of Drug Delivery Science and Technology, Journal Year: 2023, Volume and Issue: 92, P. 105325 - 105325
Published: Dec. 30, 2023
Language: Английский
Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 373, P. 252 - 264
Published: July 18, 2024
In an earlier investigation, our group introduced the TFAMoplex, a transfection agent based on mitochondrial transcription factor A (TFAM) protein, which complexes DNA into nanoparticles. The original TFAMoplex further contained bacterial phospholipase to achieve endosomal escape, and vaccinia-related kinase 1 (VRK1), significantly boosted efficiency of system by unknown mechanism. This study aims at replacing VRK1 within with dynein light chain proteins, specifically RP3, directly tether motor complex for enhanced cytosolic transport. To confirm interaction between resulting fusion we examined binding kinetics TFAM-RP3 intermediate chains 2. Furthermore, established proteomics-based assay compare protein interactions different variants, including RP3-modified version VRK1-containing system. significant shifts interactors were observed, especially nucleolar proteins. Leveraging this knowledge, incorporated one these nuclear leucine-rich repeat-containing 59 (LRRC59), in improvement properties compared comparable levels versus original, version. not only advances comprehension but also offers broader insights potential engineering designing effective gene delivery systems.
Language: Английский
Citations
4
Clinical Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown
Published: April 14, 2025
Small nucleic acid drugs including antisense oligonucleotides, small interfering RNAs, microRNAs, and aptamers, among others, have revolutionized the pharmaceutical industry in 21st century, offering novel therapeutic strategies for a myriad of diseases through precise gene expression regulation or protein synthesis modulation. As December 2024, 19 been approved globally, with applications primarily treating rare hereditary conditions, metabolic diseases, ophthalmological disorders, demonstrating great clinical potential. This review provides an overview classification, mechanism action, technical challenges, addressing drugs, focus on indications market‐available aiming to equip healthcare professionals thorough understanding practical guidance their utilization.
Language: Английский
Citations
0
ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown
Published: April 24, 2025
Lipid nanoparticles (LNPs) effectively protect mRNA and facilitate its entry into target cells for protein synthesis. Despite these successes, cellular alone may not be enough optimal expression, as translation also depends on the availability of essential metabolites, including metabolic energy sources, coenzymes, amino acids. Without adequate less efficient, potentially leading to higher dosing requirements or poorer therapeutic outcomes LNP therapies. To address this, we develop a metabolite co-delivery strategy by encapsulating metabolites within LNPs, hypothesizing that our approach can uniformly improve delivery. Instead adding fifth component organic phase, involves mixing with payload in aqueous while maintaining molar ratio components phase during formulation. We verify vitro vivo, highlighting broad applicability through mechanism efficacy studies across multiple cell lines, physiological conditions, such normoxia (i.e., 21% oxygen), hypoxia 1% mice. Taken collectively, anticipate serve generalizable enhance vivo expression using offering study treatment disease.
Language: Английский
Citations
0
Journal of drug targeting, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 32
Published: Jan. 25, 2025
The cytosolic delivery of therapeutic proteins represents a promising strategy for addressing diseases caused by protein dysfunction. Despite significant advances, efficient remains challenging due to barriers such as cell membrane impermeability, endosomal sequestration, and instability. This review summarizes recent progress in systems, including physical, chemical, biological approaches, with particular focus on strategies that enhance escape targeting specificity. We further discuss the clinical translatability these approaches propose future directions improving efficiency safety, ultimately unlocking potential intracellular proteins.
Language: Английский
Citations
0
Advanced Science, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 25, 2025
Abstract Gene delivery systems must overcome multiple barriers, with endosomal escape representing a prominent obstacle. This work has previously shown that bacterial phospholipase C (PLC) enabled of non‐viral protein‐based DNA system termed TFAMoplex. Building upon this, this introduces calcium‐responsive designed to enhance through non‐covalent capturing PLC the TFAMoplex followed by its release within endosomes and nanobody‐mediated targeting membrane. approach leads improved TFAMoplexes enabling transfection HeLa cells in full serum half maximal effective concentration (EC 50 ) less than 200 ng per mL serum, using only 5 nM PLC. Particularly, modular capture, could potentially be adapted other agents constrained poor escape. These findings present promising strategy achieve efficient escape, offering prospects for macromolecules, particular nucleic acids.
Language: Английский
Citations
0
International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown, P. 125470 - 125470
Published: March 1, 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
Chinese Chemical Letters, Journal Year: 2025, Volume and Issue: unknown, P. 111278 - 111278
Published: May 1, 2025
Language: Английский
Citations
0
Drug Delivery and Translational Research, Journal Year: 2024, Volume and Issue: 14(8), P. 2242 - 2261
Published: March 25, 2024
In the development of non-viral gene delivery vectors, it is essential to reliably localize and quantify transfected DNA inside cell. To track DNA, fluorescence microscopy methods are commonly applied. These mostly rely on fluorescently labeled binding proteins fused a fluorescent protein, or in situ hybridization (FISH). addition, co-stainings often used determine colocalization specific cellular compartments, such as endolysosomes nucleus. We provide an overview these tracking methods, advice how they should be combined, indicate which additional required draw precise conclusions from experiment. Some emphasis given localization exogenous nucleus, last step delivery. argue that suitable tools allow for nuclear detection faint signals still missing, hampering rational more efficient transfection systems.
Language: Английский
Citations
3
Microbiological Research, Journal Year: 2024, Volume and Issue: 290, P. 127963 - 127963
Published: Nov. 5, 2024
Language: Английский
Citations
2