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 →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 →Signal Transduction and Targeted Therapy2022ReviewNon-viral Gene Delivery
Qin S, Tang X, Chen Y, Et Al.
mRNA therapeutics have fuelled hope to combat incurable diseases, but insufficient understanding of mRNA instability, immunogenicity, and delivery has impeded progress. The review argues that mRNA-based drugs—especially after the COVID-19 vaccine success—can become powerful, versatile tools, and that mRNA…
Read the article →2022ReviewNon-viral Gene Delivery
Chuang St, Conklin B, Stein Jb, Pan G, Lee K-B.
Immunotherapy has improved outcomes in cancer and infectious disease, but off-target effects, systemic toxicities, and variable efficacy remain limiting. Nanoscale engineering offers ways to manipulate immune cell functions—enhancing immunity against cancers and pathogens, controlling the site of immune response, and…
Read the article →Materials Today Advances2022ReviewNon-viral Gene Delivery
Randall A. Meyer, Sarah Y. Neshat, Jordan J. Green, Jose Luis Santos, And Anthony D. Tuesca
mRNA gene therapy has broad therapeutic potential (protein replacement, vaccines, regenerative medicine, oncology), but clinical translation is limited by inadequate understanding of how to target specific organs or cell types for protein expression. Reports on material properties and administration routes are…
Read the article →Poly (beta-amino ester) as an in vivo nanocarrier for therapeutic nucleic acids.2022ReviewNon-viral Gene Delivery
Sadeqi Nezhad, M
Therapeutic nucleic acids require safe and effective in vivo delivery vectors. Most gene and cell therapies rely on ex vivo gene delivery, which is laborious, time-consuming, and costly. PBAE is a promising biodegradable synthetic cationic polymer for in vivo gene delivery due to its transfection efficiency…
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 →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 →Seminars in Immunology2021ReviewNon-viral Gene Delivery
Est-Witte Se, Livingston Nk, Omotoso Mo, Green Jj, Schneck Jp.
T cell therapies (TIL, TCR, CAR T) show clinical efficacy but are limited by high cost, lengthy ex vivo manufacturing, patient variability, and poor persistence. Nanoparticles offer a modular, universal platform to improve T cell therapy at every stage—from antigen presentation and T cell activation to T cell…
Read the article →Advanced Drug Delivery Reviews2021ReviewNon-viral Gene Delivery
Kim J, Eygeris Y, Gupta M, Sahay G.
mRNA vaccines are promising but naked mRNA is fragile, susceptible to enzymatic degradation, poorly taken up by cells due to electrostatic repulsion, and can trigger innate immune responses. Self-assembly offers a versatile approach to prepare delivery vehicles with customisable properties. The review discusses…
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 →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 →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 →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 →Expert Opinion on Drug Delivery2020ReviewNon-viral Gene Delivery
Karlsson, J.; Rhodes, K. R.; Green, J. J.; Tzeng, S. Y
Non-viral gene delivery needs safe and efficient carriers. PBAEs are biodegradable cationic polymers with promising transfection activity, but they face challenges such as instability in physiological fluids, positive-charge toxicity, and limited systemic delivery. This review summarises PBAE properties, advantages…
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 →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 →International Journal of Pharmaceutics (inferred; the supplied PDF is marked “2019ResearchNon-viral Gene Delivery
Yingqi Xu, Dingxin Liu, Jie Hu, Peirong Ding, Meiwan Chen
Triple-negative breast cancer (TNBC) lacks effective targeted therapy. Nonviral co-delivery of an anticancer drug and a therapeutic gene may improve treatment, but efficient tumour-targeted co-delivery remains challenging. TRAIL has shown limited clinical benefit alone, and embelin (EMB) can inhibit XIAP to promote…
Read the article →Bioconjugate Chemistry (likely; based on formatting and page range)2019ReviewNon-viral Gene Delivery
Samuel A. Smith, Laura I. Selby, Angus P. R. Johnston, And Georgina K. Such
Many emerging therapies require delivery of biological cargo into the cytosol, but nanoparticle delivery systems are hindered by entrapment and degradation in the endo/lysosomal pathway. Endosomal escape remains a rate-determining step for non-viral delivery. The review highlights the need for greater understanding…
Read the article →Molecules2019ReviewNon-viral Gene Delivery
Thomas, T. J.; Tajmir-Riahi, H.-A.; Pillai, C. K. S
Gene therapy requires efficient delivery of genetic material, but viral vectors carry risks of immunogenicity, toxicity, and cancer formation. Cationic polymers such as polyethyleneimine (PEI) can condense DNA and facilitate delivery, but their lack of biodegradation causes significant toxicity due to polymer…
Read the article →Journal of Controlled Release2019ReviewNon-viral Gene Delivery
Cordeiro, R. A.; Serra, A.; Coelho, J. F. J.; Faneca, H
Gene therapy requires safe and effective delivery vectors. PBAEs are biodegradable cationic polymers with excellent gene delivery properties, but a comprehensive and critical overview of their use as gene carriers is lacking. This review provides the first comprehensive and critical overview of PBAE-based gene…
Read the article →Journal of Visualized Experiments (JoVE)2018ResearchNon-viral Gene Delivery
Elana Ben-Akiva, Kelly R. Rhodes, Randall A. Meyer, Jordan J. Green
Artificial antigen-presenting cells (aAPCs) are promising for immune modulation, and anisotropic (ellipsoidal) particles have shown improved T-cell stimulation over spherical particles. However, widely used methods for generating anisotropic particles, such as thin-film stretching, can be difficult to implement…
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