Journal of Controlled Release2011ResearchNon-viral Gene Delivery
Wong Sp, Argyros O, Howe Sj, Harbottle Rp
Nonviral vectors have rarely been tested in neonatal mice because of poor delivery efficiency, yet early gene therapy could prevent irreversible disease, requires lower vector doses due to small body size, and may avoid immune reactions before immune maturation. Viral vectors carry risks such as insertional…
Read the article →2011ReviewDrug Delivery
Torchilin Vp
Lipid-based nanocarriers such as liposomes and micelles can protect drugs, reduce nonspecific toxicity, and improve pharmacokinetics, but conventional formulations are limited by rapid clearance, poor targeting, and inefficient intracellular delivery. Engineering “multifunctional pharmaceutical nanocarriers” that…
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 →International Journal of Pharmaceutics2010ResearchNon-viral Gene Delivery
Zhang Y, Li H, Sun J, Gao J, Liu W, Li B, Guo Y, Chen J
DC-Chol/DOPE cationic liposomes are efficient non-viral vectors, but the effects of DC-Chol/DOPE molar ratio, PEGylation, and serum on pDNA versus siRNA delivery were unclear. The study also aimed to test whether pDNA and siRNA have different transfection mechanisms in these liposomes. Optimal DC-Chol/DOPE molar…
Read the article →Clinical & Experimental Metastasis2010ResearchNon-viral Gene Delivery
Seo Sh, Han Hd, Noh Kh, Kim Tw, Son Sw
Chemo-immunotherapy combinations are limited by systemic immunotoxicity from cancer drugs and rapid clearance of low-molecular-weight drugs after intratumoral injection. A local, biodegradable delivery system was needed to sustain drug/GMCSF exposure at the tumour site, reduce systemic toxicity, and promote tumour…
Read the article →Clinical Cancer Research2010ResearchNon-viral Gene Delivery
Han Hd, Mangala Ls, Lee Jw, Shahzad Mmk, Kim Hs, Shen D, Nam Ej, Mora Em, Stone Rl, Lu C, Lee Sj, Roh Jw, Nick Am, Lopez-Berestein G, Sood Ak
siRNA has therapeutic potential, but in vivo delivery is limited by rapid clearance, nuclease degradation, and nonspecific distribution. A tumour-targeted, biocompatible delivery system was needed to increase intratumoral siRNA accumulation, reduce off-target effects, and enable silencing of growth-promoting genes in…
Read the article →Nature Reviews Drug Discovery2010ReviewDrug Delivery
Robby A. Petros And Joseph M. Desimone
Engineered nanoparticles have shown promise for targeted drug delivery, but first-generation systems (liposomes and polymer–drug conjugates) have not overcome all biological barriers required for effective therapy. Key barriers include opsonisation and RES clearance, inefficient cargo encapsulation and triggered…
Read the article →Journal of Internal Medicine2010ReviewNon-viral Gene Delivery
Schroeder A, Levins Cg, Cortez C, Langer R, Anderson Dg
RNAi has strong therapeutic potential, but clinical translation of siRNA is limited by delivery. siRNA is large, negatively charged, susceptible to nuclease degradation, poorly taken up by cells, and must reach the cytoplasm to engage RISC. Safe and effective lipid-based delivery systems are needed to protect siRNA…
Read the article →Journal of Microencapsulation2009ResearchDrug Delivery
Jaber Emami, Hamed Hamishehkar, Abdolhossien Rouholamini Najafabadi, Kambiz Gilani, Mohsen Minaiyan, Hamid Mahdavi, Hamid Mirzadeh, Amir Fakhari, Ali Nokhodchi
Pulmonary administration offers a route for systemic delivery of therapeutics, especially peptides and proteins, but controlled-release polymer particles are needed. Conventional w/o/w methods for hydrophilic drugs suffer from low encapsulation, protein inactivation, and difficult release control. An oil-in-oil (o/o)…
Read the article →Vaccine2008ResearchNon-viral Gene Delivery
S. Hamdy, O. Molavi, Z. Ma, A. Haddadi, A. Alshamsan, Z. Gobti, S. Elhasi, J. Samuel, A. Lavasanifar
Most PLGA-based cancer vaccine studies used foreign model antigens such as ovalbumin (OVA), which are not subject to central/peripheral tolerance and can overestimate therapeutic efficacy. There is a need to evaluate PLGA vaccines against a realistic, clinically relevant self/tumor antigen (TRP2) and to overcome…
Read the article →Journal of Controlled Release2007ResearchNon-viral Gene Delivery
Ayumi Sato, Sung Won Choi, Miwa Hirai, Asako Yamayoshi, Rui Moriyama, Takeshi Yamano, Motoki Takagi, Arihiro Kano, Akira Shimamoto, Atsushi Maruyama
Systemic siRNA therapeutics are limited by poor cell membrane permeability, rapid nuclease degradation, and renal clearance. A carrier with long circulatory half-life is needed for effective RNAi and potential tumour targeting via the enhanced permeation and retention (EPR) effect. Existing hydrophilic…
Read the article →Molecular Pharmaceutics2007ResearchNon-viral Gene Delivery
C. M. Solbrig, J. K. Saucier-Sawyer, V. Cody, W. M. Saltzman, D. J. Hanlon
Current antitumor vaccines are limited by the small number of defined tumour-associated antigens (TAAs) for most solid tumours and by poor delivery of soluble antigen to dendritic cells (DCs). Autologous whole-tumour lysates contain the full antigenic repertoire, but soluble lysates are unstable and poorly…
Read the article →Journal of Controlled Release2006ResearchNon-viral Gene Delivery
Katas H, Alpar Ho
siRNA has therapeutic potential but is limited by poor cellular uptake, rapid nuclease degradation, and poor blood stability. Chitosan was explored as a non-viral siRNA vector because of its low toxicity, biodegradability, biocompatibility, and cationic nature, but its use for siRNA delivery had not been…
Read the article →Journal of Controlled Release2006ResearchNon-viral Gene Delivery
DNA vaccines are limited by inefficient delivery to antigen-presenting cells (APCs) and lack of adjuvant effect, especially for weakly immunogenic self/tumor antigens. The study addresses this by using cationic PEI-functionalised PLGA microparticles to enhance APC activation and protective anti-tumour immunity…
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 →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 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 →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 →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…
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