Advanced Materials2009ResearchNon-viral Gene Delivery
Joel Sunshine, Jordan J. Green, Kerry P. Mahon, Fan Yang, Ahmed A. Eltoukhy, David N. Nguyen, Robert Langer, Daniel G. Anderson
Viral vectors are efficient but face safety, manufacturing, and cargo-capacity limitations. Cationic polymers such as poly(β-amino ester)s (PBAEs) are promising non-viral alternatives, but their gene delivery efficacy varies across cell types. The study asked whether small-molecule end groups on a linear PBAE could…
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 →International Journal of Pharmaceutics2008ResearchNon-viral Gene Delivery
Yongxin Yang, Zhenghong Xu, Shangwei Chen, Yu Gao, Wangwen Gu, Lingli Chen, Yuanying Pei, Yaping Li
Cationic polymers are widely studied non-viral gene vectors but generally show lower transfection efficiency than viral vectors. Endosomal escape is a major bottleneck. Histidine/imidazole-containing polymers can enhance gene expression via a “proton sponge” effect without increasing toxicity. Polyphosphazenes are…
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 →Bioorganic & Medicinal Chemistry (inferred from journal style; exact journal not stated in supplied excerpt)2007ResearchNon-viral Gene Delivery
Masato Yamagata, Takahito Kawano, Kouhei Shiba, Takeshi Mori, Yoshiki Katayama, Takuro Niidome
Gene carriers are often studied individually under different assay conditions, making direct structure–function comparisons difficult. The study compared dendritic poly(L-lysine) (KG6) and linear poly(L-lysine) (PLL) within the same experimental system to identify how carrier architecture affects DNA complex…
Read the article →Journal of Controlled Release2007ResearchNon-viral Gene Delivery
Xianfeng Zhou, Bin Liu, Xianghui Yu, Xiao Zha, Xizhen Zhang, Yu Chen, Xueyun Wang, Yinghua Jin, Yongge Wu, Yue Chen, Yaming Shan, Yan Chen, Junqiu Liu, Wei Kong, Jiacong Shen
DNA vaccines can induce antibody and CTL responses, but clinical translation is limited by weak potency and the need for high or repeated doses. The study addresses this by targeting DNA to antigen-presenting cells (APCs) and improving endosomal/lysosomal release, using mannose-bearing chitosan microspheres loaded…
Read the article →Bioconjugate Chemistry2006ResearchNon-viral Gene Delivery
Jordan J. Green, Julie Shi, Eugene Chiu, Elizaveta S. Leshchiner, Robert Langer, Daniel G. Anderson
Effective and safe gene delivery to primary endothelial cells in the presence of serum proteins is particularly challenging. Endothelial cells are important targets for cardiovascular disease and cancer, but existing nonviral vectors have low efficacy and/or cytotoxicity under serum-containing conditions. C32…
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 →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 →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 →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 →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 →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 →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 →