Science Advances2022ResearchNon-viral Gene Delivery
Rasheid Smith, Emad I. Wafa, Sean M. Geary, Kareem Ebeid, Suhaila O. Alhaj-Suliman, Aliasger K. Salem
Cancer vaccines as monotherapies have displayed limited clinical success due to the immunosuppressive tumour microenvironment (TME). Nanoscale formulations can enhance vaccine efficacy by combating TME immunosuppression, but there is a need for novel adjuvant formulations that can be combined with therapeutic cancer…
Read the article →Nature Communications2020ResearchNon-viral Gene Delivery
John C. Charpentier, Di Chen, Philip E. Lapinski, Jackson Turner, Irina Grigorova, Joel A. Swanson, Philip D. King
Macropinocytosis has been shown to regulate the growth of Ras-transformed tumour cells under amino acid (AA)-limiting conditions by providing extracellular proteins that are degraded into AA to fuel cell growth and activate mTORC1. However, whether macropinocytosis regulates the growth of non-transformed mammalian…
Read the article →Nanomedicine2020ResearchNon-viral Gene Delivery
John Choi, Yuan Rui, Jayoung Kim, Noah Gorelick, David R. Wilson, Kristen Kozielski, Antonella Mangraviti, Eric Sankey, Henry Brem, Betty Tyler, Jordan J. Green, Eric M. Jackson
Medulloblastoma (MB) and atypical teratoid/rhabdoid tumour (AT/RT) are common paediatric brain malignancies. Radiation carries high risks of developmental sequelae in young children, and current treatments remain inadequate. Viral gene therapy has safety concerns in paediatric patients, so a safe, effective nonviral…
Read the article →Nature Communications2018ResearchNon-viral Gene Delivery
Ewoud B. Compeer, Felix Kraus, Manuela Ecker, Gregory Redpath, Mayan Amiezer, Nils Rother, Philip R. Nicovich, Natasha Kapoor-Kaushik, Qiji Deng, Guerric P.B. Samson, Zhengmin Yang, Jieqiong Lou, Michael Carnell, Haig Vartoukan, Katharina Gaus, Jérémie Rossy
Polarized endocytic recycling of the T cell receptor (TCR) to the immunological synapse is essential for T cell activation, yet the cellular mechanisms that coordinate internalisation of surface receptors with sustained delivery back to the plasma membrane remain incompletely understood. The role of flotillins in…
Read the article →Drug Delivery2018ResearchDrug Delivery
Juan Chen, Xiaobing Yang, Liuqing Huang, Huixian Lai, Chuanhai Gan, Xuetao Luo
Lung cancer has the highest mortality among cancers, and single-agent chemotherapy is often unsuccessful due to drug resistance, insufficient intracellular uptake, nonspecific targeting, and severe systemic toxicity. Combination chemotherapy can suppress drug resistance and achieve synergistic anticancer efficacy…
Read the article →Nanoscale2016ResearchNon-viral Gene Delivery
Joshua J. Glass, Daniel Yuen, James Rae, Angus P. R. Johnston, Robert G. Parton, Stephen J. Kent, Robert De Rose
Investigations of nanoparticle targeting to immune cells are conventionally restricted to monocultured cell line models that lack the complexity of primary human blood cell populations, including non-specific association with, and competition from, diverse cell types. A more physiologically relevant system using…
Read the article →International Journal of Nanomedicine2015ResearchNon-viral Gene Delivery
Jing Luo, Caixia Li, Jianlin Chen, Gang Wang, Rong Gao, Zhongwei Gu
Nonviral gene carriers (cationic polymers and lipids) are promising alternatives to viral vectors, but their transfection efficiencies are much lower. While extensive efforts have focused on chemical modification of gene delivery materials, simple optimisation of the transfection procedure itself—beyond standard…
Read the article →Proceedings of the National Academy of Sciences (PNAS)2015ResearchNon-viral Gene Delivery
Tim Willinger, Matthew Staron, Shawn M. Ferguson, Pietro De Camilli, Richard A. Flavell
Prolonged T-cell receptor (TCR) signalling is required for T lymphocyte proliferation, yet TCR ligation paradoxically causes internalisation and down-modulation of the TCR from the cell surface. It is unknown how TCR signalling is sustained for many hours despite lower surface expression. Understanding whether TCR…
Read the article →International Journal of Nanomedicine2015ResearchNon-viral Gene Delivery
Zhenyu Shao, Jingyu Shao, Bingxu Tan, Shanghai Guan, Zhulong Liu, Zengjun Zhao, Fangfang He, Jian Zhao
Lung cancer chemotherapy is limited by multidrug resistance, severe adverse effects, and poor tumour targeting. A nanocarrier that actively targets lung cancer cells and co-delivers a cytotoxic drug plus therapeutic DNA could improve efficacy and reduce off-target toxicity. Tf₅ₖ-PTX-DNA-NLC: ~133 nm, zeta +19 mV…
Read the article →Bioconjugate Chemistry2014ResearchNon-viral Gene Delivery
Kim, J., Sunshine, J. C., & Green, J. J. (2014).
Nonviral gene delivery must overcome cellular uptake, endosomal escape, and nuclear transport, but the cellular uptake mechanism of poly(β-amino ester) (PBAE) polyplexes was unknown. Triple-negative breast cancer (TNBC) also lacks effective targeted therapies, making improved nonviral gene delivery strategies…
Read the article →Biochimica et Biophysica Acta (BBA) - Biomembranes2013ResearchNon-viral Gene Delivery
Fatemeh Madani, Rania Abdo, Staffan Lindberg, Hisaaki Hirose, Shiroh Futaki, Ulo Langel, Astrid Gräslund
Cell-penetrating peptides (CPPs) can internalise cells with biologically active cargo, but endosomal entrapment is a major limitation for cytoplasmic delivery, as cargo molecules must escape the endosome before degradation and acidification. While CPPs are known to enter cells via endocytosis, the background…
Read the article →Biotechnology and Bioengineering, Vol. 110, No. 3, March2013ResearchNon-viral Gene Delivery
Branching architecture is a tunable parameter for polymeric gene carriers, but how the degree of branching (DB) of bioreducible poly(amido amine)s (PAAs) affects pDNA binding, cellular uptake, endocytosis pathways, and transfection efficiency was not well defined. pDNA condensation: HBPAA completely retarded pDNA at…
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 →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 →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 →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 →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 →ResearchNon-viral Gene Delivery
Maria Buñuales, Nejat Düzgüneş, Sara Zalba, María J. Garrido & Conchita Tros De Ilarduya
Nonviral gene delivery vectors are safer than viral vectors but generally suffer from low and nonspecific transfection efficiency. EGFR is overexpressed on many tumour cells, making EGF-mediated targeting an attractive strategy to improve selectivity and gene delivery into cancer cells. EGF-lipoplexes were…
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