PNAS2012ResearchNon-viral Gene Delivery
David N. Nguyen, Kerry P. Mahon, Ghania Chikh, Phillip Kim, Hattie Chung, Alain P. Vicari, Kevin T. Love, Michael Goldberg, Steve Chen, Arthur M. Krieg, Jianzhu Chen, Robert Langer, Daniel G. Anderson
TLR7/8 agonists are promising vaccine adjuvants and antivirals, but RNA agonists are unstable and small-molecule agonists cause systemic toxicity. A delivery system specifically designed to deliver immunostimulatory RNA (isRNA) to TLR-expressing cells could enable safer and more localised innate immune activation. 14…
Read the article →Journal of Controlled Release2012ResearchNon-viral Gene Delivery
Hughes Ad, King Mr
Metastasis is the leading cause of cancer mortality, and circulating tumour cells (CTCs) are key to metastatic spread. Doxorubicin (DXR) is effective but systemically toxic and nonspecific. A targeted delivery system was needed to capture and kill CTCs under physiologically relevant flow while reducing off-target…
Read the article →Journal of Controlled Release2012ResearchNon-viral Gene Delivery
Nianxi Zhao, Jianjun Qi, Zihua Zeng, Parag Parekh, Chung-Che Chang, Ching-Hsuan Tung, Youli Zu
Suspension lymphoma/leukemia cells are notoriously hard to transfect with non-viral vectors. Existing methods such as Lipofectamine give poor plasmid DNA delivery in these cells, and viral methods raise safety concerns. A simple, efficient, biodegradable cationic polymer nanocomplex is needed for gene delivery to…
Read the article →Current Opinion in Lipidology2012ReviewNon-viral Gene Delivery
Vickers Kc, Remaley At
Extracellular miRNAs are unusually stable in plasma and their circulating levels change with disease, making them promising biomarkers. They are associated with lipid-based carriers—exosomes, microvesicles, apoptotic bodies, and lipoproteins—as well as lipid-free proteins. Whether these carriers mediate functional…
Read the article →2012ReviewNon-viral Gene Delivery
Zhang X-X, Mcintosh Tj, Grinstaff Mw
Cationic lipids are the most common non-viral gene-delivery vectors, but they generally suffer from low transfection efficiency. Functional or stimulus-responsive lipids—especially pH-, redox-, and charge-reversal-sensitive lipids—may improve nucleic acid delivery by enabling triggered cargo release, endosomal…
Read the article →Chemical Society Reviews2012ReviewDrug Delivery
Samal, S. K.; Dash, M.; Van Vlierberghe, S.; Kaplan, D. L.; Chiellini, E.; Van Blitterswijk, C.; Moroni, L.; Dubruel, P
Cationic polymers are widely studied as non-viral gene delivery vectors, but their therapeutic potential extends well beyond gene delivery. This review addresses the need for a broader overview of cationic polymers — their synthesis, modification, bioactive properties, architectures, and applications in drug…
Read the article →African Journal of Biotechnology2011ResearchNon-viral Gene Delivery
Wang B, Zhou J, Cui S, Yang B, Zhao Y, Zhao B, Duan Y, Zhang S
Although cationic liposomes are widely used non-viral gene vectors, the structure–activity relationships governing their transfection efficiency remain poorly understood, and optimisation is still largely trial-and-error. A systematic in vitro study was needed to correlate lipoplex physicochemical properties and…
Read the article →Journal of Controlled Release2011ResearchNon-viral Gene Delivery
Tae-Il Kim, Thomas Rothmund, Thomas Kissel, Sung Wan Kim
Endosomal escape remains a major barrier for polymeric gene delivery. Arginine-grafted bioreducible polymers (ABPs) show high transfection via cell-penetrating arginine, but the effect of adding endosome-buffering moieties on their biophysical and transfection properties was not well defined. Buffering capacity…
Read the article →Biomacromolecules2011ResearchNon-viral Gene Delivery
Joel C. Sunshine, Marib I. Akanda, David Li, Kristen L. Kozielski, Jordan J. Green
Non-viral gene delivery needs safer and more effective polymeric vectors. Poly(β-amino ester)s (PBAEs) are promising, but previous studies had not systematically modified all three structural elements—backbone, side chain, and end group—within one library to analyse how small structural changes affect transfection…
Read the article →Proceedings of the National Academy of Sciences of the United States of America (PNAS)2011ResearchDrug Delivery
Che-Ming J. Hu, Li Zhang, Santosh Aryal, Connie Cheung, Ronnie H. Fang, Liangfang Zhang
Long-circulating nanoparticles are needed for sustained systemic drug delivery, but PEGylation—the current stealth gold standard—can face anti-PEG immune responses. A top-down biomimetic approach using natural erythrocyte membranes could better mimic red blood cells (RBCs), nature’s long-circulating carriers, while…
Read the article →Nanomedicine: Nanotechnology, Biology, and Medicine2011ResearchNon-viral Gene Delivery
Shashi Prasad, Virginia Cody, Jennifer K. Saucier-Sawyer, W. Mark Saltzman, Clarence T. Sasaki, Richard L. Edelson, Martin A. Birchall, Douglas J. Hanlon
Efficient antigen delivery remains a major challenge for dendritic cell (DC)-based immunotherapy of solid-organ malignancies. Soluble tumour lysates suffer from instability, poor DC internalisation, and inefficient cross-presentation to cytotoxic T lymphocytes. PLGA nanoparticles may protect antigens, improve…
Read the article →Biomaterials2011ResearchNon-viral Gene Delivery
Dai J, Zou S, Pei Y, Cheng D, Ai H, Shuai X
PEI is an effective gene carrier but high-molecular-weight PEI is nonbiodegradable and cytotoxic; PLL is biodegradable but lacks proton-buffering capacity, has low transfection efficiency, and is also cytotoxic. A vector combining the complementary strengths of PEI and PLL is needed. Cytotoxicity: At 100 µg/mL, PPL…
Read the article →Journal of Controlled Release2011ResearchNon-viral Gene Delivery
Yanan Yue, Fan Jin, Rui Deng, Jinge Cai, Zhuojun Dai, Marie C.M. Lin, Hsiang‐fu Kung, Maria Ahlm Mattebjerg, Thomas Lars Andresen, Chi Chung Wu
PEI is one of the best nonviral gene delivery vectors, but why it works so well remains unclear. In particular, the role of free, uncomplexed PEI chains and their length in transfection, cellular uptake, and endosomal escape has not been quantitatively resolved, and the “proton sponge” mechanism is increasingly…
Read the article →Biomaterials2011ResearchNon-viral Gene Delivery
Stephany Y. Tzeng, Hugo Guerrero‐cazares, Elliott E. Martinez, Joel C. Sunshine, Alfredo Quiñones‐hinojosa, Jordan J. Green
Glioblastoma (GB) has poor survival and current therapies are insufficient. Viral gene therapy carries safety risks, while nonviral vectors often lack efficiency and practical storage stability. PBAEs had shown high transfection and low toxicity in other cell types but had not been tested in primary brain tumour…
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 →Journal of Drug Delivery2011ReviewNon-viral Gene Delivery
Daniel A. Balazs, W.T. Godbey
Liposomes are versatile, biocompatible vesicular carriers that can encapsulate and deliver DNA or RNA, but the relationship between lipid charge, lipid packing, and gene-delivery efficiency remains complex. This review discusses physical packing parameters and specific lipids used for gene delivery, classified by…
Read the article →2011ReviewNon-viral Gene Delivery
Kim, T.-I.; Kim, S. W
Bioreducible polymers containing disulfide linkages are attractive gene-delivery carriers because they are stable in the oxidizing extracellular environment but degrade rapidly in the reducing intracellular cytosol via thiol–disulfide exchange, triggered by high glutathione (GSH) levels. This review addresses the…
Read the article →Acta Pharmacologica Sinica2010ResearchNon-viral Gene Delivery
Jian Li, Ying-Zi He, Wen Li, Yun-Zhen Shen, Yu-Ru Li, Yun-Feng Wang
Non-viral gene delivery systems offer advantages in safety and ease of preparation over viral vectors, but suffer from limited transfection efficiency. While polymer-lipid hybrid nanoparticles (PLN) have shown promise as non-viral vectors, the incorporation of PEGylated lipids to enhance circulation time and…
Read the article →2010ResearchNon-viral Gene Delivery
Kai K. Ewert, Alexandra Zidovska, Ayesha Ahmad, Nathan F. Bouxsein, Heather M. Evans, Christopher S. Mcallister, Charles E. Samuel, Cyrus R. Safinya
Cationic lipid–nucleic acid (CL-NA) complexes are promising non-viral vectors for gene delivery and siRNA-mediated silencing, but their transfection and silencing efficiencies remain low compared with viral vectors. A major gap is poor mechanistic understanding of how complex structure, membrane charge density, and…
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 →Proceedings of the National Academy of Sciences of the United States of America (PNAS)2010ResearchNon-viral Gene Delivery
Fan Yang, Seung-Woo Cho, Sun Mi Son, Said R. Bogatyrev, Deepika Singh, Jordan J. Green, Ying Mei, Sohyun Park, Suk Ho Bhang, Byung-Soo Kim, Robert Langer, Daniel G. Anderson
Stem cell therapy for angiogenesis is limited by insufficient expression of angiogenic factors and poor cell viability after transplantation. Viral gene delivery raises safety concerns, while non-viral methods often suffer from low transfection efficiency and toxicity. A safe, efficient, biodegradable polymeric…
Read the article →Biomaterials2010ResearchNon-viral Gene Delivery
Nupura S. Bhise, Ryan S. Gray, Joel C. Sunshine, Soe Htet, Andrew J. Ewald, Jordan J. Green
Non-viral gene delivery vectors are safer alternatives to viral vectors but often suffer from low transfection efficiency, especially in hard-to-transfect primary cells and 3-D tissue models. There is a need to understand how small changes in polymer structure—specifically terminal functionalisation and molecular…
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…
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