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 →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 →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 →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 →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 →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 →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 →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 →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…
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…
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