Biomaterials2005ResearchDrug Delivery
Norbert Dinauer, Sabine Balthasar, Carolin Weber, Jörg Kreuter, Klaus Langer, Hagen Von Briesen
Antibody-based therapeutics have shown promise in targeting specific cell types, but their efficacy can be enhanced by conjugation to drug carriers. Nanoparticles as drug carriers offer advantages including high drug loading capacity, controlled release, and protection from degradation. However, achieving selective…
Read the article →Biochimica et Biophysica Acta (BBA) - Biomembranes2005ResearchNon-viral Gene Delivery
Mattias Hallbrink, Johannes Oehlke, Gisela Papsdorf, Michael Bienert
Cell-penetrating peptides (CPPs) efficiently translocate across plasma membranes and are promising delivery vectors for therapeutic macromolecules. However, the influence of cell state, density, and peptide-to-cell ratio on CPP uptake and degradation has received little attention. Understanding whether CPP uptake is…
Read the article →Gene Therapy2005ReviewNon-viral Gene Delivery
Dean Da, Strong Dd, Zimmer We.
Nonviral gene delivery is limited by multiple extracellular and intracellular barriers, but the nuclear envelope remains a major unresolved barrier, especially in nondividing cells. Plasmids must enter the nucleus to be transcribed, yet the mechanisms of plasmid nuclear import are much less understood than protein…
Read the article →Expert Opinion on Drug Delivery2005ReviewNon-viral Gene Delivery
Sérgio Simões, Ana Da Silva Filipe, Henrique Faneca, Miguel Mano, Nuno Penacho, Nejat Düzgüneş, Maria C. Pedroso De Lima
Cationic liposome–DNA complexes (lipoplexes) are a potentially viable non-viral alternative to viral vectors for therapeutic gene delivery, but they suffer from limited delivery/gene expression efficiency, toxicity at higher concentrations, adverse interactions with serum and cell surfaces, and poor tissue access…
Read the article →Nature Reviews Drug Discovery2005ReviewNon-viral Gene Delivery
Pack, D. W.; Hoffman, A. S.; Pun, S.; Stayton, P. S
The lack of safe and efficient gene-delivery methods remains a limiting obstacle to human gene therapy. Synthetic vectors are safer than recombinant viruses but generally lack sufficient efficacy, so polymers must be rationally designed to overcome extracellular and intracellular delivery barriers. PEI: Only 15–20%…
Read the article →Advanced Drug Delivery Reviews2005ReviewNon-viral Gene Delivery
Ying Waeckerle-Men And Marcus Groettrup
Dendritic cell (DC)-based vaccines are limited by the short persistence of MHC class I/peptide complexes on the DC surface—often only a few hours—when soluble peptides are loaded exogenously. This short presentation limits CTL activation and vaccine efficacy. The authors investigated biodegradable PLGA microspheres…
Read the article →Synthesis of Poly(β-amino esters) Optimized for Highly Effective Gene Delivery.2003ResearchNon-viral Gene Delivery
Akinc, A., Anderson, D. G., Lynn, D. M., & Langer, R. (2003).
Nonviral polymeric gene delivery vectors need systematic optimisation of nonstructural factors—polymer molecular weight, chain end-group, and polymer/DNA ratio—that strongly influence transfection, cytotoxicity, and DNA complexation. These factors had not been comprehensively studied together for poly(β-amino…
Read the article →Trends in Immunology2002ReviewNon-viral Gene Delivery
James Harris, Dirk Werling, Jayne C. Hope, Geraldine Taylor, Chris J. Howard
Caveolae and caveolin are cholesterol-rich membrane microdomains involved in endocytosis, cholesterol regulation, and signal transduction, but their presence and function in immune cells have been contentious. This review addresses the need to clarify the distribution and roles of caveolae/caveolin in mammalian…
Read the article →Molecular Therapy2001ResearchNon-viral Gene Delivery
Adi Mesika, Irina Grigoreva, Muriel Zohar, Ziv Reich
Transfection efficiency of nonviral gene delivery systems remains unacceptably low, largely due to the inability of plasmid DNA to effectively translocate through the nuclear pore complexes (NPCs). While substantial progress has been made in transcriptionally regulated vectors, control over nuclear targeting is…
Read the article →Journal of Biological Chemistry2001ResearchNon-viral Gene Delivery
Ge Liu, Maria Molas, Gregory A. Grossmann, Murali Pasumarthy, Jose C. Perales, Mark J. Cooper, Richard W. Hanson
Receptor-mediated gene transfer using ligand–poly-L-lysine–DNA complexes requires DNA to be condensed into small particles for efficient cellular uptake and expression. However, the relationship between NaCl concentration, the mode of poly-L-lysine binding to DNA, the resulting condensed DNA structure, and…
Read the article →Gene Therapy2001ResearchNon-viral Gene Delivery
Primary lymphoid cells, especially human peripheral blood mononuclear cells (PBMC), are very difficult to transfect with viral and nonviral vectors. There is a need for efficient nonviral, receptor-mediated gene delivery to PBMC for cell-based therapies and for studying gene function in primary lymphocytes. Naive vs…
Read the article →2001ReviewNon-viral Gene Delivery
Kircheis, R.; Wightman, L.; Wagner, E
PEI is one of the most effective non-viral gene delivery polymers, but its efficacy, toxicity, and in vivo behaviour depend strongly on molecular weight, branching, particle size, surface charge, and modifications. This review addresses how PEI/DNA complexes can be modified with targeting ligands, shielding agents…
Read the article →Gene Therapy1999ResearchNon-viral Gene Delivery
J Vacik, Bs Dean, We Zimmer, Da Dean
Non-viral gene therapy vectors lack efficient cell-specific targeting, with most approaches focusing only on cell surface internalisation rather than nuclear delivery. The nuclear import of plasmid DNA is a critical barrier to gene expression, yet it has been largely overlooked in vector design. A method to achieve…
Read the article →Gene Therapy1999ResearchNon-viral Gene Delivery
Sérgio Simões, Vladimir Slepushkin, Pedro Pires, Rogério Gaspar, Maria C. Pedroso De Lima & Nejat Düzgüneş
Cationic liposome–DNA complexes (lipoplexes) are safer than viral vectors but have limited transfection efficiency, toxicity at high doses, and sensitivity to serum/extracellular negatively charged macromolecules. The study asks whether targeting ligands or pH-sensitive fusogenic peptides can improve…
Read the article →Journal of Controlled Release1999ResearchNon-viral Gene Delivery
Daqing Wang, Deborah R. Robinson, Glen S. Kwon, John Samuel
Naked plasmid DNA vaccination is largely limited to intramuscular, cutaneous, and intradermal routes because naked DNA is ineffective at crossing mucosal barriers and is rapidly degraded by nucleases. Delivery systems that protect plasmid DNA and target it to antigen-presenting cells are needed for mucosal DNA…
Read the article →1999ReviewNon-viral Gene Delivery
Godbey, W. T.; Wu, K. K.; Mikos, A. G
Gene therapy still lacks safe and efficient delivery vectors. PEI has emerged as a promising non-viral polycation because it condenses DNA and mediates endosomal escape, but its transfection mechanism, targeting potential, and toxicity require clearer understanding. This review summarises PEI chemistry, PEI/DNA…
Read the article →Journal of Controlled Release1998ResearchNon-viral Gene Delivery
Young Hun Choi, Feng Liu, Jin-Seok Kim, Young Kweon Choi, Jong Sang Park, Sung Wan Kim
Non-viral gene delivery systems such as poly-L-lysine (PLL) have low immunogenicity compared with viral vectors, but PLL suffers from poor biocompatibility, rapid degradation, and low transfection efficiency. PEGylation was explored to improve solubility, reduce cytotoxicity, and enhance cell permeability for gene…
Read the article →Molecular Membrane Biology1998ReviewNon-viral Gene Delivery
Hope Mj, Mui B, Ansell S, Ahkong Qf
Polymeric nucleic acid drugs—plasmid DNA, antisense oligonucleotides, and ribozymes—require protection from nucleases and efficient intracellular delivery to cytoplasm/nucleus. Viral vectors are efficient but immunogenic and safety-limited; non-viral cationic lipid systems are promising, but the mechanism of…
Read the article →Gene Therapy1997ResearchNon-viral Gene Delivery
S. Li And L. Huang
First-generation cationic liposome–DNA complexes showed insufficient in vivo gene transfer efficiency. A more virus-like, self-assembling non-viral vector was needed that could condense and protect plasmid DNA and produce efficient gene expression after systemic administration. LPD gave consistently higher in vivo…
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 →Journal of Biological Chemistry1987ResearchNon-viral Gene Delivery
Yasuhiro Minami, Lawrence E. Samelson, Richard D. Klausner
The T cell antigen receptor (TCR) plays a critical role in T cell activation, but the dynamics of TCR internalisation and its regulation were poorly understood. It was known that phorbol esters (activators of protein kinase C) lead to loss of surface TCRs, but the mechanisms—whether internalisation was…
Read the article →Cellular Immunology1981ResearchNon-viral Gene Delivery
Hans-Jörg Heiniger, Arnold Sodergren, Jan D. Marshall
While pinocytosis (endocytosis) in lymphocytes had been qualitatively described using electron microscopy, quantitative measurements of endocytic activity and its relationship to immunological function were lacking. Understanding whether endocytosis correlates with T cell differentiation and cytotoxic function is…
Read the article →ResearchNon-viral Gene Delivery
Maria Buñuales, Nejat Düzgüneş, Sara Zalba, María J. Garrido & Conchita Tros De Ilarduya
Nonviral gene delivery vectors are safer than viral vectors but generally suffer from low and nonspecific transfection efficiency. EGFR is overexpressed on many tumour cells, making EGF-mediated targeting an attractive strategy to improve selectivity and gene delivery into cancer cells. EGF-lipoplexes were…
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