Molecular Therapy2016ResearchNon-viral Gene Delivery
Ans De Beuckelaer, Charlotte Pollard, Sandra Van Lint, Kenny Roose, Lien Van Hoecke, Thomas Naessens, Vimal Kumar Udhayakumar, Muriel Smet, Niek Sanders, Stefan Lienenklaus, Xavier Saelens, Siegfried Weiss, Guido Vanham, Johan Grooten & Stefaan De Koker
mRNA vaccines are promising for inducing cytolytic CD8⁺ T cell responses, and lipoplex carriers improve mRNA delivery to dendritic cells. However, the innate factors that regulate T cell induction by mRNA lipoplex vaccines remain unresolved. In particular, type I interferons (IFNs) are induced by mRNA but can either…
Read the article →Journal of Controlled Release2016ResearchNon-viral Gene Delivery
Matthias Van Woensel, Nathalie Wauthoz, Rémi Rosière, Véronique Mathieu, Róbert Kiss, Florence Lefranc, Brecht Steelant, Ellen Dilissen, Stefaan W. Van Gool, Thomas Mathivet, Holger Gerhardt, Karim Amighi, Steven De Vleeschouwer
Galectin-1 (Gal-1) is overexpressed in glioblastoma multiforme (GBM), promotes tumour progression, angiogenesis, chemoresistance, and immune suppression. A non-invasive delivery strategy is needed to reach CNS tumours with siRNA while limiting systemic effects. The intranasal route was explored as an underexplored…
Read the article →Advanced Drug Delivery Reviews2015ReviewNon-viral Gene Delivery
Yunching Chen, Dong-Yu Gao, Leaf Huang
miRNAs can simultaneously regulate multiple cancer-related genes, making them attractive therapeutic agents or targets. However, efficient, specific, and safe systemic delivery of therapeutic miRNAs in vivo remains a major challenge due to rapid degradation, poor tumour penetration, immunotoxicity, endosomal…
Read the article →Cell Chemical Biology (Chemistry & Biology)2015ResearchNon-viral Gene Delivery
Skye Zeller, Chang Seon Choi, Pradeep D. Uchil, Hong-Seok Ban, Alyssa Siefert, Tarek M. Fahmy, Walther Mothes, Sang-Kyung Lee, Priti Kumar
Arginine-rich cell-penetrating peptides (CPPs) such as nona-arginine (9R) can effectively translocate covalently attached biomolecules into cells, but poorly deliver electrostatically complexed siRNA, with most CPP:siRNA complexes trapped in endosomes. The mechanism by which ligand attachment to 9R overcomes this…
Read the article →Proceedings of the National Academy of Sciences (PNAS)2015ResearchNon-viral Gene Delivery
Tim Willinger, Matthew Staron, Shawn M. Ferguson, Pietro De Camilli, Richard A. Flavell
Prolonged T-cell receptor (TCR) signalling is required for T lymphocyte proliferation, yet TCR ligation paradoxically causes internalisation and down-modulation of the TCR from the cell surface. It is unknown how TCR signalling is sustained for many hours despite lower surface expression. Understanding whether TCR…
Read the article →Journal of Controlled Release 200 (2015ResearchNon-viral Gene Delivery
H. Akita Et Al.
Cationic gene carriers can mediate cellular uptake but often show poor post-nuclear transcription/translation, toxicity, and aggregation in blood. The study aimed to develop a systemically applicable, tumour-targeting gene carrier that is neutral in blood/cytosol but becomes cationic in endosomes for endosomal…
Read the article →Chemical Reviews2015ReviewNon-viral Gene Delivery
Ulrich Lächelt And Ernst Wagner
Therapeutic nucleic acids—including plasmid DNA, mRNA, siRNA, miRNA, antisense oligonucleotides, and aptamers—have broad therapeutic potential, but their delivery to the correct intracellular site of action remains the dominant bottleneck. Polyplexes, formed by electrostatic complexation of nucleic acids with…
Read the article →Cancer Biology & Therapy2014ResearchNon-viral Gene Delivery
Paulina Wyrozumska, Justyna Meissner, Monika Toporkiewicz, Marta Szarawarska, Kazimierz Kuliczkowski, Maciej Ugorski, Marta A. Walasek & Aleksander F. Sikorski
Most cancer gene therapy research has focused on solid tumours, while blood cancers such as leukaemia and lymphoma have received less attention. There is a need for a lipid carrier that protects antisense oligonucleotides or plasmid DNA from enzymatic degradation, is stable in serum, has low toxicity, and can…
Read the article →Nature Reviews Genetics2014ReviewNon-viral Gene Delivery
Yin H, Kanasty Rl, Eltoukhy Aa, Vegas Aj, Dorkin Jr, Anderson Dg.
Gene-based therapy has potential to treat a wide range of diseases, but clinical success is limited by delivery barriers. Viral vectors, while efficient, carry risks of carcinogenesis, immunogenicity, broad tropism, limited packaging capacity, and manufacturing difficulties. Non-viral vectors offer improved safety…
Read the article →BioMed Research International.2014ReviewNon-viral Gene Delivery
Torrecilla J, Rodríguez-Gascón A, Solinís Má, Del Pozo-Rodríguez A
Naked RNAi molecules are rapidly degraded by serum nucleases and cannot readily cross cell membranes because of their negative charge. Effective delivery systems are therefore required to exploit RNAi for antiviral therapy. Lipid nanoparticles (LNPs) are attractive because they are relatively safe, simple to produce…
Read the article →PLoS ONE2012ResearchNon-viral Gene Delivery
Sunshine, J. C., Sunshine, S. B., Bhutto, I., Handa, J. T., & Green, J. J. (2012).
Retinal pigment epithelial (RPE) cells are difficult to transfect, and existing nonviral reagents achieve only low efficiency in vitro. Improved nonviral gene delivery to RPE could benefit both laboratory studies and ocular gene therapy. Lead in vitro efficacy: B5-S5-E7 at 60 w/w transfected 44 ± 5% of ARPE-19 cells…
Read the article →Pharmazie.2011ReviewNon-viral Gene Delivery
Cationic liposomes (CLs) are attractive non-viral gene-delivery carriers because they are safer, less immunogenic, and easier to prepare than viral vectors, but their transfection efficiency (TE) remains low and the relationship between lipoplex physicochemical properties, lipoplex–cell interaction, and TE is poorly…
Read the article →Proceedings of the National Academy of Sciences of the United States of America2010ResearchNon-viral Gene Delivery
Kevin T. Love, Kerry P. Mahon, Christopher G. Levins, Kathryn A. Whitehead, William Querbes, J. Robert Dorkin, June Qin, William Cantley, Liu Liang Qin, Timothy Racie, Maria Frank-Kamenetsky, Ka Ning Yip, Rene Alvarez, Dinah W. Y. Sah, Antonin De Fougerolles, Kevin Fitzgerald, Victor Koteliansky, Ak
Existing siRNA delivery systems required high doses (1 mg/kg) for hepatic gene silencing. A more potent, well-tolerated lipid-like delivery material was needed to enable low-dose RNAi therapeutics and multi-gene silencing in vivo. C12-200 enabled Factor VII silencing at doses below 0.01 mg/kg in mice, 100-fold more…
Read the article →Journal of Controlled Release2010ResearchNon-viral Gene Delivery
IL-12 gene therapy is attractive for cancer because local IL-12 expression can prime anti-tumour immunity while reducing systemic toxicity. However, non-viral gene delivery to tumours is inefficient, and simple sonoporation using ultrasound alone does not achieve sufficient cancer gene therapy. The authors tested…
Read the article →British Journal of Pharmacology2009ReviewNon-viral Gene Delivery
Midoux P, Pichon C, Yaouanc J-J, Jaffrès P-A
Non-viral nucleic acid delivery systems—lipoplexes, polyplexes, and lipopolyplexes—are limited mainly by poor endosomal escape. The review examines whether histidine- and imidazole-containing carriers can exploit the acidic endosomal environment to destabilize membranes and improve cytosolic delivery of DNA, mRNA…
Read the article →Proceedings of the National Academy of Sciences1989ResearchNon-viral Gene Delivery
Malone Rw, Felgner Pl, Verma Im
RNA transfection was inefficient and restricted because intact RNA was difficult to obtain and rapidly degraded. In vitro transcription could now supply large amounts of RNA, creating a need for a reliable method to introduce RNA into cells and study translational efficiency and mRNA stability. Transfection of 10 ng…
Read the article →1989ReviewNon-viral Gene Delivery
Felgner Pl, Ringold Gm
Existing polynucleotide delivery methods—calcium phosphate, DEAE-dextran, electroporation, retroviral vectors—had limitations in convenience, reproducibility, efficiency, and applicability across cell types. A simple, broadly effective cationic liposome reagent was needed for DNA and RNA transfection of mammalian…
Read the article →ReviewNon-viral Gene Delivery
The transferrin receptor (TfR) is overexpressed on many cancer cells and is efficiently internalised, making it a useful target for delivering small-molecule drugs and nucleic acid therapeutics while reducing non-target effects. The review summarises TfR biology, Tf-lipoplex development, and therapeutic applications…
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