International Journal of Nanomedicine2023ResearchNon-viral Gene Delivery
Hannah J Vaughan, Camila G Zamboni, Kathryn M Luly, Ling Li, Kathleen L Gabrielson, Laboni F Hassan, Nicholas P Radant, Pranshu Bhardwaj, Florin M Selaru, Martin G Pomper, Jordan J Green
Hepatocellular carcinoma (HCC) has limited treatment options, with modest survival after systemic chemotherapy or transarterial chemoembolization (TACE). Gene therapies hold promise for treating HCC, but delivery remains a critical hurdle. While poly(beta-amino ester) (PBAE) nanoparticles have shown efficacy in…
Read the article →Science2022ResearchNon-viral Gene Delivery
Joel G. Rurik, István Tombácz, Amir Yadegari, Pedro O. Méndez Fernández, Swapnil V. Shewale, Li Li, Toru Kimura, Ousamah Younoss Soliman, Tyler E. Papp, Ying K. Tam, Barbara L. Mui, Steven M. Albelda, Ellen Puré, Carl H. June, Haig Aghajanian, Drew Weissman, Hamideh Parhiz, Jonathan A. Epstein
Fibrosis affects millions of people with cardiac disease and contributes to heart failure. While adoptive transfer of CAR T cells targeting fibroblast activation protein (FAP) has shown promise in reducing cardiac fibrosis, conventional CAR T cells persist for months to years and could cause chronic off-target…
Read the article →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 →Frontiers in Pharmacology2022ResearchNon-viral Gene Delivery
Sajid Iqbal, Alessandro Francisco Martins, Muhammad Sohail, Jingjing Zhao, Qi Deng, Muhan Li, Zhongxi Zhao
Polymeric gene delivery vectors require detailed physicochemical characterisation to ensure reproducible formulation and efficient transfection. PBAE-447 is a promising biodegradable cationic polymer, but its simple nanoparticles can degrade or aggregate in aqueous/physiological conditions. This study characterises…
Read the article →Advanced Science (Weinh.)2021ResearchNon-viral Gene Delivery
Johan Karlsson, Stephanie Y. Tzeng, Shayan Hemmati, Kathryn M. Luly, Olivia Choi, Yuan Rui, David R. Wilson, Kristen L. Kozielski, Alfredo Quiñones-Hinojosa, Jordan J. Green
Systemic delivery of RNA therapeutics with polymer-based nanocarriers is limited by poor colloidal stability in blood and inefficient intracellular delivery of siRNA to the cytosol. There is a need for nanoparticles that remain stable extracellularly but rapidly release RNA intracellularly. Crosslinking: Molecular…
Read the article →International Journal of Polymeric Materials and Polymeric Biomaterials2021ResearchNon-viral Gene Delivery
Liu T, Lin M, Wu F, Lin A, Luo D, Zhang Z
siRNA therapeutics are limited by poor cellular uptake, serum nuclease degradation, and inefficient endosomal/lysosomal escape. Chitosan is biocompatible and biodegradable but has low transfection efficiency, largely due to poor buffering capacity and weak endosomal escape. Histidine grafting was explored to add…
Read the article →Materials Science and Engineering: C2021ResearchDrug Delivery
Jiayu Zhou, Yishu Zhai, Jumei Xu, Tian Zhou, Lian Cen
PLGA microspheres are widely used for controlled drug release, but they often exhibit pronounced initial or mid-term burst release. A strategy is needed to finely tune drug release kinetics and suppress burst release, especially for water-soluble drugs. MSNs: Average size 119 nm; specific surface area 902.53 m²/g…
Read the article →Nature Communications2021ResearchNon-viral Gene Delivery
Julia Koerner, Dennis Horvath, Valerie L. Herrmann, Anna Mackeracher, Bruno Gander, Hideo Yagita, Jacques Rohayem, Marcus Groettrup
Cancer immunotherapy needs potent, pharmaceutically defined, GMP-compatible adjuvants for clinical translation. Poly(I:C) is a widely used TLR3 agonist but has ill-defined structure, heterogeneity, pyrogen contamination, and toxicity concerns. Riboxxim is a well-defined 100-bp double-stranded RNA with a…
Read the article →Bioengineering2021ResearchNon-viral Gene Delivery
Rodgers, T., Muzzio, N., Watson, C., & Romero, G. (2021).
Gene-editing tools are large plasmid constructs that cannot spontaneously enter mammalian cells, and viral vectors are limited by cargo size, immunogenicity, and manufacturing challenges. PBAE nanoparticles are promising nonviral carriers, but unmodified PEG-PDHA nanoparticles release encapsulated plasmid DNA too…
Read the article →2020ResearchNon-viral Gene Delivery
Vitor Francisco, Catarina Rebelo, Artur Filipe Rodrigues, Josephine Blersch, Hugo Fernandes, Lino Ferreira
Non-viral vectors such as nanoparticles (NPs) show promise for RNA-based therapies, but suffer from limited cell targeting, poor cellular internalisation, and inadequate endolysosomal escape capacity. The field lacks a systematic, high-throughput approach to identify effective polymeric nanocarriers that can deliver…
Read the article →Acta Biomaterialia (Published by Elsevier Ltd on behalf of Acta Materialia Inc.)2020ResearchNon-viral Gene Delivery
Kelly R. Rhodes, Randall A. Meyer, Justin Wang, Stephany Y. Tzeng, Jordan J. Green
Regulatory T cell (Treg)-based therapeutics show promise for treating autoimmune diseases and preventing transplant rejection, but adoptive Treg transfer is expensive, complex, and difficult to implement. "Off-the-shelf" non-cellular alternatives that can induce endogenous Tregs in vivo are needed. Existing…
Read the article →ACS Applied Materials & Interfaces2020ResearchNon-viral Gene Delivery
Kwang-Soo Kim, Jun-Hyeok Han, Seung Hee Choi, Hae-Yun Jung, Joo Dong Park, Hee-Jung An, Seong-Eun Kim, Dong-Hyun Kim, Junsang Doh, Dong Keun Han, Ik-Hwan Kim, Wooram Park, Kyung-Soon Park
Natural killer (NK) cells are promising for cancer immunotherapy due to their lower risk of cytokine storm and graft-versus-host disease compared to T cell therapies. However, existing NK cell activation strategies—genetic engineering and cytokine treatment—are inefficient, expensive, and involve complex processing…
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 →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 →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 →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)…
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)…
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