Advanced Healthcare Materials2013ResearchNon-viral Gene Delivery
Stephany Y. Tzeng, Jordan J. Green
Non-viral polymeric gene delivery to human brain cancer cells is often limited by low efficacy and poor understanding of how polymer structure should be tuned for different nucleic acid cargos. Glioblastoma has a poor prognosis, and improved delivery of DNA and siRNA could enable new therapies. DNA delivery: Leading…
Read the article →J. Phys. Chem. B2013ResearchNon-viral Gene Delivery
Tiia-Maaria Ketola, Martina Hanzlíková, Linda Leppänen, Manuela Raviña, Corey J. Bishop, Jordan J. Green, Arto O. Urtti, Helge J. Lemmetyinen, Marjo L. Yliperttula, Elina Vuorimaa
The structure–activity relationships governing polyplex formation by PEI and PLL are not well understood, especially whether DNA binding is independent or cooperative and how pH affects the mechanism. This limits rational design of nonviral gene delivery vectors. Polyplex core formation was complete at approximately…
Read the article →European Journal of Pharmaceutics and Biopharmaceutics2013ResearchNon-viral Gene Delivery
A.L. Silva, R.A. Rosalia, A. Sazak, M.G. Carstens, F. Ossendorp, J. Oostendorp, W. Jiskoot
Overlapping synthetic long peptides (SLPs) are promising for therapeutic cancer vaccination, but Montanide-based formulations have limitations including non-biodegradability, local side effects, poorly controlled release, and limited scalability. PLGA nanoparticles (NPs) offer a biodegradable alternative, but…
Read the article →2013ResearchNon-viral Gene Delivery
Tzeng, S. Y., Higgins, L. J., Pomper, M. G., & Green, J. J. (2013).
Liver cancer has limited curative options, and transarterial chemoembolization (TACE) provides local access for gene therapy. However, prior nonviral delivery strategies suffered from low in vitro efficacy and high toxicity to healthy liver cells. There is a need for a delivery platform that efficiently transfects…
Read the article →Small2012ResearchNon-viral Gene Delivery
Nupura S. Bhise, Ron B. Shmueli, Jose Gonzalez, Jordan J. Green
Non-viral polymeric nanoparticles are promising for gene therapy and stem cell reprogramming, but the number of plasmids complexed per particle affects transfection efficiency and co-delivery of multiple plasmids. Existing methods for quantifying plasmids per particle have significant drawbacks, and few studies have…
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 →Molecular Pharmaceutics (inferred from known publication record; journal name not explicitly stated in supplied file)2012ResearchNon-viral Gene Delivery
Joel C. Sunshine, Daniel Y. Peng, Jordan J. Green
Non-viral gene delivery requires a better understanding of which polymer properties enable nanoparticles to overcome intracellular barriers. Poly(beta-amino ester)s (PBAEs) are promising, but the mechanisms behind their effectiveness—especially the roles of buffering capacity, degradation rate, and end-group…
Read the article →PLoS ONE2012ResearchNon-viral Gene Delivery
Sunshine, J. C., Sunshine, S. B., Bhutto, I., Handa, J. T., & Green, J. J. (2012).
Retinal pigment epithelial (RPE) cells are difficult to transfect, and existing nonviral reagents achieve only low efficiency in vitro. Improved nonviral gene delivery to RPE could benefit both laboratory studies and ocular gene therapy. Lead in vitro efficacy: B5-S5-E7 at 60 w/w transfected 44 ± 5% of ARPE-19 cells…
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 →International Journal of Nanomedicine (Dove Press open-access article; exact citation details not fully provided in the 2011ResearchNon-viral Gene Delivery
Stephany Y. Tzeng, Peter H. Yang, Warren L. Grayson, Jordan J. Green
Human umbilical vein endothelial cells (HUVECs) are relevant to tissue engineering, cancer therapy, and angiogenesis-related diseases. Non-viral vectors are safer than viruses but often less efficient. Biodegradable poly(ester amine) (PEA) and poly(amido amine) (PAA) nanoparticles were developed and screened for…
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 →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 →Pharmaceutical Research2011ResearchNon-viral Gene Delivery
Samar Hamdy, Azita Haddadi, Anooshirvan Shayeqanpour, John Samuel, Afsaneh Lavasanifar
Mannosylation of vaccine formulations is a promising strategy to target antigens to the mannose receptor (MR) on dendritic cells (DCs), potentially improving antigen uptake, processing, and presentation. While PLGA nanoparticles (NPs) are established vaccine delivery vehicles, the effect of chemical conjugation of…
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 →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 →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 →Journal of Controlled Release2010ResearchNon-viral Gene Delivery
Luis J. Cruz, Paul J. Tacken, Remco Fokkink, Ben Joosten, Martien Cohen Stuart, Fernando Albericio, Ruurd Torensma, Carl G. Figdor
Antibody-mediated targeting of vaccine components to dendritic cells (DCs) enhances vaccine efficacy, but linking multiple antigens and immune modulators to a single antibody is limited. Slow-release PLGA particles conjugated to DC-specific antibodies could overcome this by delivering large antigen payloads and…
Read the article →Biomaterials2009ResearchNon-viral Gene Delivery
Chen Guihua, Chen Wenjie, Wu Zhuang, Yuan Renxu, Li Hua, Gao Jinming, Shuai Xintao
Gene therapy could induce immunosuppression with greater durability and less toxicity than conventional agents like cyclosporine A, but T cells are notoriously refractory to non-viral gene delivery. An effective, T-cell-targeted, MRI-trackable non-viral vector is needed for immunosuppression in transplantation and…
Read the article →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…
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