Molecular Therapy2020ResearchNon-viral Gene Delivery
Xiaojing Shi, Qinqin Cheng, Tianling Hou, Menglu Han, Goar Smbatyan, Julie E. Lang, Alan L. Epstein, Heinz-Josef Lenz, Yong Zhang
Exosomes are nanosized membranous vesicles with unique properties (abundant membrane proteins, high biocompatibility, low immunogenicity) that make them attractive for therapeutic development. While exosomes have been studied as drug delivery vehicles, fewer studies have focused on engineering exosome surface…
Read the article →Nature Communications2020ResearchNon-viral Gene Delivery
N.N. Parayath, S.B. Stephan, A.L. Koehne, P.S. Nelson, M.T. Stephan
CAR T and TCR T cell therapies are powerful but face prohibitive costs and manufacturing complexity due to the need for leukapheresis, ex vivo transduction, expansion, and quality control—all under GMP conditions. An "off-the-shelf" injectable nanocarrier that can transiently reprogram circulating T cells in vivo…
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 →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 →Cancer Immunology Research (AACR)2020ResearchNon-viral Gene Delivery
Dylan J. Drakes, Sarwish Rafiq, Terence J. Purdon, Andrea V. Lopez, Smita S. Chandran, Christopher A. Klebanoff, Renier J. Brentjens
T-cell receptor (TCR)-modified T-cell gene therapy can target a variety of extracellular and intracellular tumour-associated antigens, yet has had little clinical success. A potential explanation for limited antitumor efficacy is a lack of T-cell activation in vivo, particularly when tumour cells downregulate…
Read the article →Proceedings of the National Academy of Sciences (PNAS)2020ResearchNon-viral Gene Delivery
Bradley Vis, Rachel E. Hewitt, Tom P. Monie, Camilla Fairbairn, Suzanne D. Turner, Stephen D. Kinrade, Jonathan J. Powell
Ultrasmall silica nanoparticles (USSN, <10 nm diameter) were recently shown to stimulate T lymphocytes directly at relatively low exposure doses, but the underlying mechanisms and associated cell signalling were unknown. Understanding whether USSN directly engage the T cell receptor (TCR) complex or act through other…
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 →Acta Biomaterialia2020ResearchNon-viral Gene Delivery
Yusuke Sato, Nana Okabe, Yusuke Note, Kazuki Hashiba, Masatoshi Maeki, Manabu Tokeshi, Hideyoshi Harashima
Small-sized lipid nanoparticles (LNPs) are attractive for tissue penetration but often lose potency because lipid components diffuse out and serum proteins adsorb onto poorly packed surfaces. The study asked how the hydrophobic scaffold structure of pH-sensitive cationic lipids affects small-LNP stability, lipid…
Read the article →Angewandte Chemie International Edition2020ResearchNon-viral Gene Delivery
Xuewei Zhao, Jinjin Chen, Min Qiu, Yamin Li, Zachary Glass, Qiaobing Xu
In vivo engineering of T lymphocytes is limited by poor transfection efficiency and reliance on ex vivo electroporation. A non-viral mRNA delivery platform that can target primary T cells in vivo is needed for CAR T-cell therapy, vaccines, and immunotherapy. Rough screening identified imidazole head 93 with O17O…
Read the article →Bioconjugate Chemistry2020ResearchNon-viral Gene Delivery
Margaret M. Billingsley, Nathan Singh, Pranali Ravikumar, Rui Zhang, Carl H. June, Michael J. Mitchell
CAR T cell therapy currently relies on viral vectors or electroporation for T cell engineering. Viral vectors cause permanent CAR expression and carry safety/manufacturing limitations, while electroporation is cytotoxic and requires specialised equipment. A safer, efficient non-viral mRNA delivery platform for human…
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 Controlled Release2020ResearchNon-viral Gene Delivery
Nour Shobaki, Yusuke Sato, Yuichi Suzuki, Nana Okabe, Hideyoshi Harashima
Tumour-associated macrophages (TAMs) are largely M2-like and promote tumour growth, angiogenesis, metastasis, and immune suppression. There is a need for systemic delivery systems that can target TAMs and manipulate their pro-tumour functions with siRNA for cancer immunotherapy. Optimised CL4H6-LNPs had 90% siRNA…
Read the article →Science Advances2020ResearchNon-viral Gene Delivery
Elana Ben-Akiva, Randall A. Meyer, Hongzhe Yu, Jonathan T. Smith, Drew M. Pardoll, Jordan J. Green
Previous red blood cell (RBC) membrane-coated nanoparticles have all been spherical, missing the physical shape component of biomimicry. Particle shape is a critical design parameter affecting biodistribution, macrophage evasion, and targeted interactions. A platform combining physical biomimicry (anisotropic shape)…
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 →Nature Communications2020ResearchNon-viral Gene Delivery
Siddharth Patel, N. Ashwanikumar, Ema Robinson, Yan Xia, Cosmin Mihai, Joseph P. Griffith Iii, Shangguo Hou, Adam A. Esposito, Tatiana Ketova, Kevin Welsher, John L. Joyal, Örn Almarsson, Gaurav Sahay
Endosomal sequestration of lipid-based nanoparticles (LNPs) remains a formidable barrier to delivery, with only <2% of LNPs reaching the cytosol. The role of cholesterol structure in LNP-mediated mRNA delivery and endosomal escape was poorly understood. There is a need to decode the structural characteristics of…
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 →ACS Applied Bio Materials2020ResearchNon-viral Gene Delivery
Coralie M. Backlund, Christopher R. Hango, Lisa M. Minter, Gregory N. Tew
Intracellular protein and antibody delivery is limited by inefficient carriers, high toxicity, and a frequent requirement for serum-free conditions, especially in difficult-to-transfect cells such as immune cells, stem cells, and neurons. A simple noncovalent carrier that works in complete media and across diverse…
Read the article →Polymer Chemistry (Royal Society of Chemistry)2020ResearchDrug Delivery
Lu Sun, Hua Wei, Xiaoshuo Zhang, Chao Meng, Guiying Kang, Wei Ma, Liwei Ma, Baoyan Wang, Cuiyun Yu
Folic acid (FA)-mediated active targeting improves nanocarrier tumour specificity but exposes targeting ligands to the immune system, causing rapid clearance and nonspecific uptake. Existing acid-labile benzoic-imine PEG sheddable systems are insufficiently stable at physiological pH. A more stable, tumour-triggered…
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 →Frontiers in Bioengineering and Biotechnology2020ResearchDrug Delivery
Serkan Yaman, Harish Ramachandramoorthy, Gizem Oter, Daria Zhukova, Tam Nguyen, Manoj K. Sabnani, Jon A. Weidanz, Kytai T. Nguyen
Melanoma is an aggressive skin cancer with limited treatment efficacy due to non-specific drug targeting, severe side effects, and multidrug resistance. Current cell-based immunotherapies are costly, complex, and carry long-term autoimmune risks. There is a need for a targeted, biocompatible drug delivery system that…
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)…
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