Angewandte Chemie International Edition2020ReviewNon-viral Gene Delivery
Shuangqian Yan, Zichao Luo, Zhenglin Li, Yu Wang, Jun Tao, Changyang Gong, Xiaogang Liu
Cancer immunotherapy has improved clinical outcomes, but few patients show adequate response rates and long-term responses, and systemic side effects remain common due to the dynamic nature of the immune system. Biomaterial-assisted immunotherapy is a promising approach to improve therapeutic efficacy and reduce side…
Read the article →PNAS* (*Proceedings of the National Academy of Sciences*)2020ReviewNon-viral Gene Delivery
Stephany Y. Tzeng, Kisha K. Patel, David R. Wilson, Randall A. Meyer, Kelly R. Rhodes, Jordan J. Green
Cancer immunotherapy has shown clinical success but remains limited by low response rates, high cost, and the need for ex vivo cell manipulation or prior knowledge of patient-specific tumour antigens. A broadly applicable, antigen-agnostic strategy that genetically reprograms tumour cells in situ—without ex vivo…
Read the article →Applied Materials Today2020ResearchNon-viral Gene Delivery
Jing Zhao, Danping Lu, Sergio Moya, Haoying Yan, Miaojuan Qiu, Junzong Chen, Xincheng Wang, Yang Li, Haobo Pan, Guochuang Chen, Guocheng Wang
Bispecific T-cell engager (BiTE) immunotherapy is a promising cancer treatment, but clinical application is limited by high production costs and short in vivo half-life of BiTE proteins. A gene delivery system that enables sustained in vivo expression of BiTE could overcome these limitations, but existing non-viral…
Read the article →Cancers (MDPI)2020ResearchNon-viral Gene Delivery
Julie J.-J. Tang, Alina P. Sung, Mariel J. Guglielmo, Laura N.-G., Doug Redelman, James Smith-Gagen, Diane Hudig
Monoclonal antibody anti-tumour therapies rely on NK cell-mediated antibody-dependent cell-mediated cytotoxicity (ADCC), but patient responses vary widely. While tumour antigen escape is one cause of treatment failure, the role of inter-individual variation in NK cell serial killing capacity—the ability of a single…
Read the article →Biomaterials Science (accepted manuscript; manuscript ID BM-ART-09-2020ResearchNon-viral Gene Delivery
Rui Zhang, Rakan El-Mayta, Timothy Murdoch, Claude Warzecha, Margaret Billingsley, Sarah Shepherd, Ningqiang Gong, Lili Wang, James Wilson, Daeyeon Lee, Michael J. Mitchell
LNP delivery to liver versus spleen is difficult to predict from formulation parameters, and the role of helper phospholipids in biodistribution and protein adsorption is incompletely understood. This study probed how helper lipid identity (DOPE vs DSPC) affects LNP accumulation in liver/spleen and interactions with…
Read the article →Journal of Controlled Release2020ResearchNon-viral Gene Delivery
Pedro P. Guimaraes, Rui Zhang, Roman Spektor, Mingchee Tan, Amanda Chung, Margaret M. Billingsley, Rakan El-Mayta, Rachel S. Riley, Lili Wang, James M. Wilson, Michael J. Mitchell
LNP libraries are usually screened in vitro, which poorly predicts in vivo mRNA delivery. A high-throughput in vivo platform was needed to screen many LNP formulations simultaneously and identify lead carriers for functional mRNA delivery. b-mRNA could be detected in liver at doses as low as 17 ng; b-mRNA delivery…
Read the article →Journal of Materials Chemistry B2020ResearchNon-viral Gene Delivery
Yana Tarakanchikova, Albert Muslimov, Igor Sergeev, Kirill Lepik, Nikita Yolshin, Alexander Goncharenko, Kirill Vasilyev, Igor Eliseev, Anton Bukatin, Vladislav Sergeev, Sergey Pavlov, Alexey Popov, Igor Meglinski, Boris Afanasyev, Bogdan Parakhonskiy, Gleb Sukhorukov, Dmitry Gorin
DNA- and mRNA-based therapies are transforming biomedicine, but intracellular delivery—especially to hard-to-transfect, clinically relevant cells such as primary human T lymphocytes—remains a major barrier. Existing non-viral methods often suffer from low transfection efficiency, high toxicity, or complex…
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 Biotechnology2020ResearchNon-viral Gene Delivery
David N. Nguyen, Theodore L. Roth, P. Jonathan Li, Peixin Amy Chen, Ryan Apathy, Murad R. Mamedov, Linda T. Vo, Victoria R. Tobin, Daniel Goodman, Eric Shifrut, Jeffrey A. Bluestone, Jennifer M. Puck, Francis C. Szoka, Alexander Marson
CRISPR-Cas9 genome editing in clinically relevant primary cells is limited by inefficient homology-directed repair (HDR) and cytotoxicity of exogenous DNA. Improvements are needed to increase editing efficiency, cell viability, and generalizability across cell types for adoptive cell therapies and research. tCTS…
Read the article →Materials Science & Engineering C2020ResearchNon-viral Gene Delivery
Yingxi Lu, Fapu Wu, Weihua Duan, Xueluer Mu, Sha Fang, Nana Lu, Xianfeng Zhou, Wei Kong
DNA vaccines require high doses because naked DNA is poorly delivered to antigen-presenting cells (APCs), and conventional PLGA microsphere encapsulation by W/O/W emulsion can damage DNA, lower supercoiled DNA content, and give low encapsulation efficiency. A controlled-release system is needed that protects DNA…
Read the article →International Journal of Nanomedicine2020ResearchNon-viral Gene Delivery
CAR-T cell therapy is limited by complex manufacturing, viral vector use, high cost, and severe toxicities. A nonviral, transient CAR modification approach using self-assembled nanoparticles could provide a simpler, safer, and potentially broadly applicable alternative for T-cell engineering. Formulation screening…
Read the article →Science Translational Medicine2020ResearchNon-viral Gene Delivery
Xueguang Lu, Lei Miao, Wenting Gao, Ziqi Chen, Kevin J. Mchugh, Yehui Sun, Zachary Tochka, Stephanie Tomasic, Kaitlyn Sadtler, Alain Hyacinthe, Yuxuan Huang, Tyler Graf, Quanyin Hu, Morteza Sarmadi, Robert Langer, Daniel G. Anderson, Ana Jaklenec
STING agonists require frequent intratumoral injections over months to achieve efficacy, leading to poor patient adherence, repeated disruption of the tumour microenvironment, increased metastasis risk, and limited applicability to hard-to-reach tumours. A single-injection delivery system that mimics multiple dosing…
Read the article →ACS Biomaterials Science & Engineering (as indicated in the supplied file header; exact volume/pages and DOI were not in2020ResearchNon-viral Gene Delivery
Denis Routkevitch, Deepti Sudhakar, Marranne Conge, Mahita Varanasi, Stephany Y. Tzeng, David R. Wilson, Jordan J. Green
The mechanism by which cationic polymers with titratable amines mediate endosomal escape and cytosolic delivery of nucleic acids remains poorly understood. Buffering capacity alone has often failed to predict transfection efficacy, so the study examines whether the effective pKa of poly(beta-amino ester)s (PBAEs)…
Read the article →ACS Biomaterials Science & Engineering (as indicated in the file header; exact volume/pages and DOI were not included in2020ResearchNon-viral Gene Delivery
Denis Routkevitch, Deepti Sudhakar, Marranne Conge, Mahita Varanasi, Stephany Y. Tzeng, David R. Wilson, Jordan J. Green
The mechanism by which cationic polymers with titratable amines mediate endosomal escape and cytosolic delivery of nucleic acids remains poorly understood. Buffering capacity alone has often failed to predict transfection efficacy, so this study examines whether the effective pKa of poly(beta-amino ester)s (PBAEs)…
Read the article →Molecular Therapy: Nucleic Acids2020ResearchNon-viral Gene Delivery
Rui Yan Yuan, Mahita Varanasi, Shanelle Mendes, Hannah M. Yamagata, David R. Wilson, Jordan J. Green
CRISPR-Cas9 gene editing requires efficient intracellular delivery of large cargo. Viral vectors have packaging and production limitations, and nonviral CRISPR plasmid delivery had mainly been studied for single-site knockout, not for gene deletion requiring two cleavage events. The transfection requirements for…
Read the article →Bioconjugate Chemistry2020ReviewNon-viral Gene Delivery
Francia V, Schiffelers Rm, Cullis Pr, Witzigmann D
LNPs are clinically advanced vectors for siRNA, mRNA, and DNA delivery, but their in vivo behaviour is strongly influenced by the biological environment. Upon administration, biomolecules adsorb to the LNP surface and form a “biomolecular corona,” which defines the particle’s biological identity, affects stability…
Read the article →2020ReviewNon-viral Gene Delivery
Liu C, Zhang L, Dong N, Zhang W, Chen X, Gao R, Sun H.
Cationic liposomes (CLs) are promising non-viral gene-delivery vectors, but their clinical use in cancer gene therapy is limited by extracellular barriers (opsonisation, RES clearance, poor tumour penetration) and intracellular barriers (endosomal/lysosomal entrapment, restricted cytoplasmic/nuclear transport). The…
Read the article →International Journal of Nanomedicine2020ReviewNon-viral Gene Delivery
Chen, C.-K.; Huang, P.-K.; Law, W.-C.; Chu, C.-H.; Chen, N.-T.; Lo, L.-W
Gene therapy is limited by the fragile nature of therapeutic DNA/RNA and by safety concerns with viral vectors. Non-viral polymeric vectors are attractive, but conventional cationic polymers such as PEI, PDMAEMA, and PLL are often non-degradable, causing accumulation, cytotoxicity, and poor gene unpacking. This…
Read the article →Pharmaceutics2020ReviewNon-viral Gene Delivery
Wahane A, Waghmode A, Kapphahn A, Dhur K, Gupta A, Bahal R
Nucleic acid analogs and genome-editing proteins have broad therapeutic potential, but clinical translation is limited by poor cell- and organ-specific delivery, endosomal entrapment, enzymatic degradation, and short bioavailability. The review examines lipid- and polymer-based non-viral vectors as strategies to…
Read the article →Nature Reviews Immunology2019ReviewNon-viral Gene Delivery
Søren R. Paludan, Line S. Reinert, Veit Hornung
DNA in abnormal cellular compartments (cytosol, endosomes, micronuclei) is a potent danger signal for the innate immune system, primarily known for inducing type I interferons and IL-1β. More recently, it has become clear that cytosolic DNA also triggers various forms of programmed cell death (PCD), but the pathways…
Read the article →Biomaterials Science2019ResearchNon-viral Gene Delivery
Brynn R. Olden, Emmeline Cheng, Yilong Cheng, Suzie H. Pun
T cells are an important target for ex vivo gene delivery and editing, but most commercial reagents cannot transfect them and cationic polymers show only moderate success. The specific intracellular barriers limiting non-viral gene delivery to human T cells are poorly understood, hindering rational polymer design…
Read the article →American Journal of Translational Research (Am J Transl Res)2019ResearchNon-viral Gene Delivery
CAR-T cell therapy relies mainly on retroviral/lentiviral vectors, which carry risks of carcinogenicity and complex manufacturing. PiggyBac transposon systems offer a safer, simpler non-viral alternative for stable transgene expression, but primary T lymphocytes are difficult to transfect efficiently. A polymeric…
Read the article →Molecular Pharmaceutics2019ResearchNon-viral Gene Delivery
Wilson, D. R., Rui, Y., Siddiq, K., Routkevitch, D., & Green, J. J. (2019).
Nonviral gene delivery remains limited by low transfection efficacy, especially under physiological serum conditions and at low nanoparticle doses. Although linear poly(β-amino ester)s (PBAEs) are effective, branching structure had not been systematically evaluated in well-defined PBAE-like poly(ester amine) systems…
Read the article →2019ReviewNon-viral Gene Delivery
Majumder J, Et Al.
Conventional systemic drug administration suffers from low site-specific bioavailability, unfavourable biodistribution, poor target accumulation, and adverse side effects. There is a need for carrier-based systems that enable localised and targeted delivery, improve therapeutic efficacy, and reduce toxicity…
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