The inclusion of poly(ethylene glycol) monolaurate in liposomes formulated with dimyristoyl-sn-glycero-3-phosphocholine and certain cationic gemini surfactants improves their capability of condensing DNA into a psi phase and transfecting it into cells. Both the condensation, observed by circular dichroism, and the transfection efficiency are strongly effected by the protocol of inclusion of the polymer in the formulations. The highest transfection efficiency is observed in correspondence of the highest extent of DNA condensation.
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http://dx.doi.org/10.1021/jm061260f | DOI Listing |
Sci Transl Med
January 2025
College of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang University, Hangzhou 310058, China.
Macrophages play a central role in antitumor immunity, making them an attractive target for gene therapy strategies. However, macrophages are difficult to transfect because of nucleic acid sensors that can trigger the degradation of foreign plasmid DNA. Here, we developed a macrophage-specific editing (MAGE) system by which compact plasmid DNA encoding a CasRx editor can be delivered to macrophages by a poly(β-amino ester) (PBAE) carrier to bypass the DNA sensor and enable RNA editing in vitro and in vivo.
View Article and Find Full Text PDFCurr Gene Ther
January 2025
Research Group Medical Biotechnology & Bioengineering, TH Köln - University of Applied Sciences, Leverkusen, Germany.
Gamma-Retroviral (RVVs) and lentiviral vectors (LVVs) represent indispensable tools in somatic gene therapy, mediating the efficient, stable transfer of therapeutic genes into a variety of human target cells. LVVs, in contrast to RVVs, are capable of stably genetically modifying non-proliferating target cells, making them the superior instrument in cell and gene therapy. To date, the LVV manufacturing process employs human embryonic kidney cells (HEK293) and derivatives thereof transiently transfected with multiple plasmids encoding the required viral vector components.
View Article and Find Full Text PDFMol Ther Nucleic Acids
March 2025
Comprehensive Bone Marrow Failure Center, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Fanconi anemia (FA) is a congenital multisystem disorder characterized by early-onset bone marrow failure (BMF) and cancer susceptibility. While gene addition and repair therapies are being considered as treatment options, depleted hematopoietic stem cell (HSC) pools, poor HSC mobilization, compromised survival during transduction, and increased sensitivity to conventional conditioning strategies limit eligibility for FA patients to receive gene therapies. As an alternative approach, we explored protein replacement by mRNA delivery via lipid nanoparticles (LNPs).
View Article and Find Full Text PDFHeliyon
January 2025
School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Schwann cells, as crucial regenerative cells, possess the ability to facilitate axon growth following peripheral nerve injury. However, the regeneration efficiency dominated by Schwann cells is impaired by factors such as the severity of peripheral nervous injury, aging, and metabolic disease. Cause the limitations of clinical treatments, it is necessary to urgently search for new substances that could reinforce the functionality of Schwann cells and promote nerve regeneration.
View Article and Find Full Text PDFCurr Gene Ther
January 2025
Department of Chemistry and Environmental Sciences, IBILCE, São Paulo State University - UNESP, São José do Rio Preto, São Paulo, Brazil.
Introduction: The clinical translation of chitosan-based formulations for siRNA delivery has been partially limited by their poor stability/solubility at physiological conditions, although they have good biocompatibility and cost-effectiveness.
Method: In this study, the chitosan was O-substituted with diisopropylethylamine (DIPEA) groups, which improved its solubility at pH 7.4 by increasing the degree of ionization and enhanced the ability of chitosan to load siRNA at very low amine/phosphate (N/P) ratios.
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