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 →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 →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 →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 →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…
Read the article →Advanced Healthcare Materials (Adv. Healthcare Mater.)2018ResearchNon-viral Gene Delivery
Sungjin Min, Yoonhee Jin, Chen Yuan Hou, Jayoung Kim, Jordan J. Green, Taek Jin Kang, Seung-Woo Cho
Current cancer treatments (chemotherapy, radiotherapy) suffer from a lack of selectivity for tumour cells, causing severe side effects and therapeutic resistance. While gene therapy is a promising alternative, viral vectors pose safety risks (immunogenicity, tumorigenicity), and nonviral vectors often suffer from low…
Read the article →Biomacromolecules2018ResearchDrug Delivery
Jayoung Kim, James G. Shamul, Sagar R Shah, Alyssa Shin, Ben J Lee, Alfredo Quiñones‐hinojosa, Jordan J. Green
Many anticancer small molecules have poor aqueous solubility, and verteporfin (VP) has mainly been used as a photodynamic therapy agent, which carries photosensitivity and delivery limitations. PBAE-based materials have been developed extensively for nucleic acid delivery but are less explored for non-genetic…
Read the article →Nature Communications2017ResearchNon-viral Gene Delivery
H.F. Moffett, M.E. Coon, S. Radtke, S.B. Stephan, L. Mcknight, A. Lambert, B.L. Stoddard, H.P. Kiem, M.T. Stephan
Therapies based on genetically engineered immune cells (CAR T cells, HSCs) are transforming medicine, but the viral and electroporation methods used to create these cytoreagents are complex, expensive, and time-consuming. There is a growing need for transient "hit-and-run" genetic programming (transcription factors…
Read the article →International Journal of Pharmaceutics2017ResearchNon-viral Gene Delivery
Genada Sinani, Melike Sessevmez, M. Koray Gök, Saadet Özgümüş, Alper Okyar, H. Oya Alpar, Erdal Cevher
Mucosal vaccination can stimulate both mucosal and systemic immunity, but free protein antigens generally induce poor systemic immune responses and require adjuvants. There is a need for a safe, effective nasal vaccine carrier that improves antigen stability, uptake, and immunogenicity, especially for poorly…
Read the article →Journal of Controlled Release2017ResearchNon-viral Gene Delivery
Camila G. Zamboni, Kristen L. Kozielski, Hannah J. Vaughan, Maisa M. Nakata, Jayoung Kim, Luke J. Higgins, Martin G. Pomper, Jordan J. Green
Hepatocellular carcinoma (HCC) has poor survival and standard therapies are limited by off-target toxicity to healthy hepatocytes and drug resistance. Gene therapy is promising, but non-viral vectors often suffer from poor intracellular delivery and lack of cancer specificity. A biodegradable polymeric nanoparticle…
Read the article →Journal of Biomedical Materials Research Part A2017ResearchNon-viral Gene Delivery
Wilson, D. R., Et Al. (2017).
Clinical translation of biomaterial-based gene delivery nanoparticles is limited by efficacy, safety, batch-to-batch consistency, scalable manufacturing, and long-term storage stability. Continuous microfluidic fabrication may overcome manufacturing and scale-up challenges for biodegradable PBAE/DNA polyplexes. DNA…
Read the article →Journal of Controlled Release2016ResearchDrug Delivery
Cong Zhang, Tong An, Dan Wang, Guoyun Wan, Mingming Zhang, Hemei Wang, Sipei Zhang, Rongshan Li, Xiaoying Yang, Yinsong Wang
Hepatocellular carcinoma (HCC) has poor prognosis and limited effective systemic therapy. Combination antiangiogenesis and chemotherapy with paclitaxel (PTX) and combretastatin A4 (CA4) is synergistic, but both drugs have poor solubility, lack tumour targeting, and cause systemic toxicity. A tumour…
Read the article →Acta Biomaterialia2016ResearchNon-viral Gene Delivery
Kim, J., Kang, Y., Tzeng, S. Y., & Green, J. J. (2016).
Small cell lung cancer (SCLC) has high recurrence and mortality, and new therapies are needed. PBAE/DNA polyplexes are effective nonviral vectors but aggregate in physiological and acidic buffers, limiting therapeutic utility. PEGylation can improve stability but often reduces cellular uptake and transfection—the…
Read the article →ACS Nano2015ResearchNon-viral Gene Delivery
Antonella Mangraviti, Stephany Yi Tzeng, Kristen Lynn Kozielski, Yuan Wang, Yike Jin, David Gullotti, Mariangela Pedone, Nitsa Buaron, Ann Liu, David R. Wilson, Sarah K. Hansen, Fausto J. Rodriguez, Guo-Dong Gao, Francesco Dimeco, Henry Brem, Alessandro Olivi, Betty Tyler, Jordan J. Green
Glioblastoma remains highly lethal with poor prognosis despite surgery, radiation, and chemotherapy. Gene therapy is a promising alternative, but viral vectors carry safety risks. Non-viral polymeric nanoparticles are safer but have historically shown poor in vivo efficacy. A biodegradable poly(beta-amino ester)…
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 →ACS Applied Materials & Interfaces (Just Accepted Manuscript)2013ResearchNon-viral Gene Delivery
Cuicui Li, Stephany Y. Tzeng, Liane E. Tellier, Jordan J. Green
DNA-based therapeutics require an intracellular delivery system to be effective. For diseases like brain cancer—where local access to residual tumour is often available following surgical resection—an implantable device that enables both controlled release and intracellular delivery of DNA could open new…
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