A water-soluble polyphosphonium polymer was synthesized and directly compared with its ammonium analog in terms of siRNA delivery. The triethylphosphonium polymer shows transfection efficiency up to 65% with 100% cell viability, whereas the best result obtained for the ammonium analog reaches only 25% transfection with 85% cell viability. Moreover, the nature of the alkyl substituents on the phosphonium cations is shown to have an important influence on the transfection efficiency and toxicity of the polyplexes. The present results show that the use of positively charged phosphonium groups is a worthy choice to achieve a good balance between toxicity and transfection efficiency in gene delivery systems.
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http://dx.doi.org/10.1021/ja207366k | DOI Listing |
Extracellular vesicles (EVs) are gaining recognition as promising therapeutic carriers for immune modulation. We investigated the potential of EVs derived from HEK293FT cells to stabilize and deliver interleukin-10 (IL-10), a key anti-inflammatory cytokine. Using minicircle (MC) DNA vectors, we achieved IL-10 overexpression and efficient incorporation into EVs, yielding superior stability compared to free, recombinant IL-10 protein.
View Article and Find Full Text PDFMol Ther
January 2025
Perinatal Institute, Division of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA. Electronic address:
Exemplified by successful use in COVID-19 vaccination, delivery of modified mRNA encapsulated in lipid nanoparticles provides a framework for treating various genetic and acquired disorders. However, lipid nanoparticles that can deliver mRNA into specific lung cell types have not yet been established. Here, we sought whether poly(®-amino ester)s (PBAE) or PEGylated PBAE (PBAE-PEG) in combination with 4A3-SC8/DOPE/cholesterol/DOTAP lipid nanoparticles (LNP) could deliver mRNA into different types of lung cells in vivo.
View Article and Find Full Text PDFBiotechnol J
January 2025
Department of Biological Sciences, KAIST, Daejeon, Republic of Korea.
Increasing demand for adeno-associated virus (AAV) used in gene therapy highlights the need to enhance AAV production. When intracellular AAV2 and extracellular AAV9 were produced in HEK293T cells using the triple transfection method, apoptosis occurred during the AAV production. To mitigate apoptosis induced by AAV production, the pro-apoptotic BAX/BAK1 genes were knocked out in HEK293T cells.
View Article and Find Full Text PDFViruses
December 2024
School of Veterinary Medicine, Xinjiang Agricultural University, Urumqi 830052, China.
Canids act as a crucial intermediary in the transmission of rabies and , serving as co-infection hosts and pathogen carriers for both rabies and hydatid disease (HD) transmitted from animals to humans. Therefore, an effective and efficient bivalent oral vaccine for preventing HD and rabies is urgently required to reduce economic losses in husbandry resulting from rabies and HD. In this study, a full-length plasmid (pcDNA4-NPM+G+EgM123+eGFP+L) carrying the gene and fluorescence reporter genes of eGFP and four auxiliary transfection plasmids of rabies virus SRV (pcDNA4-N, pcDNA4-P, pcDNA4-G, pcDNA-L) were established by reverse genetics approaches and co-transfected to BSR cells by electrotransfection.
View Article and Find Full Text PDFPharmaceutics
January 2025
School of Pharmacy, Changzhou University, Changzhou 213164, China.
Non-viral vectors have gained recognition for their ability to enhance the safety of gene delivery processes. Among these, polyethyleneimine (PEI) stands out as the most widely utilized cationic polymer due to its accessibility. Traditional methods of modifying PEI, such as ligand conjugation, chemical derivatization, and cross-linking, are associated with intricate preparation procedures, limited transfection efficiency, and suboptimal biocompatibility.
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