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 →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 →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 →ResearchDrug Delivery
Kevin J. Kauffman, Clement Do, Sadhana Sharma, Matthew D. Gallovic, Eric M. Bachelder, Kristy M. Ainslie
Acetalated dextran (Ac-DEX) is a pH-sensitive, biodegradable polymer useful for drug delivery, but it degrades to methanol, which can be toxic at high concentrations or with repeated dosing. A safer analog that degrades to ethanol instead of methanol is needed for high-volume clinical applications such as multiple…
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