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 →Biotechnology and Bioengineering (accepted manuscript)2021ResearchNon-viral Gene Delivery
Emily Harris, Devon Zimmerman, Eric Warga, Anil Bamezai, Jacob Elmer
Retroviral gene delivery for T cell therapies is expensive, semi-randomly integrating, and variable between patients. Non-viral alternatives are needed, but T cells are notoriously hard to transfect, especially primary T cells. Lipofectamine LTX was the best vehicle in Jurkat cells; optimised conditions in X-VIVO…
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 →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 →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 →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 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 →International Journal of Molecular Sciences2018ResearchNon-viral Gene Delivery
Simon A. B. Riedl, Alexander Raup, Patrick Kaiser, Christopher V. Synatschke, Valerie Jérôme, Ruth Freitag
Genetic modification of human T lymphocytes is critical for both basic research and emerging therapies (e.g., CAR-T cells), but established non-viral methods are highly inefficient. Linear polyethylenimine (l-PEI), the "gold standard" for non-viral transfection of mammalian cells, achieves only single-digit…
Read the article →Molecular Pharmaceutics (Just Accepted Manuscript)2018ResearchNon-viral Gene Delivery
David P. Walsh, Robert D. Murphy, Angela Panarella, Rosanne M. Raftery, Brenton Cavanagh, Jeremy C. Simpson, Fergal J. O’brien, Andreas Heise, Sally-Ann Cryan
Tissue engineering needs efficient, biocompatible non-viral gene delivery to mesenchymal stem cells (MSCs), which are inherently refractory to transfection. Existing vectors have limitations: PEI is cytotoxic and linear poly(L-lysine) (L-PLL) has poor transfection efficiency. Transfection efficiency (pGFP, day 7)…
Read the article →PLOS ONE2017ResearchNon-viral Gene Delivery
Susanne Przybylski, Michaela Gasch, Anne Marschner, Marcus Ebert, Alexander Ewe, Gisa Helmig, Nadja Hilger, Stephan Fricke, Susanne Rudzok, Achim Aigner, Jana Burkhardt
Nanoparticle-based gene delivery methods are promising for transfecting immune cells, but their impact on basic immune functions such as proliferation—a cornerstone of cellular immunity—has not been systematically investigated. Understanding whether transfection reagents non-specifically influence immune cell…
Read the article →Colloids and Surfaces B: Biointerfaces2017ResearchNon-viral Gene Delivery
Pinnapireddy Sr, Duse L, Strehlow B, Schäfer J, Bakowsky U
Polyethylenimine (PEI)-based gene delivery is limited by cytotoxicity, rapid degradation, and low cellular uptake. A safer, more stable non-viral system was needed for both gene delivery and gene knockdown. Physicochemical properties: DDC liposomes ~198.7 nm, ζ = −30.9 mV; IPEI polyplexes ~166.2 nm, ζ = +19.1 mV…
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 →Biomacromolecules2016ResearchNon-viral Gene Delivery
Yongsheng Gao, Jian-Yuan Huang, Jonathan O’keeffe Ahern, Lara Cutlar, Dezhong Zhou, Feng‐huei Lin, Wenxin Wang
Nonviral gene delivery vectors suffer from an “efficacy–toxicity paradox”: high transfection efficiency usually comes with high cytotoxicity, while low-toxicity vectors often transfect poorly. For cationic polymers such as PEI, PAMAM, and PDMAEMA, increasing molecular weight typically improves transfection but also…
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 →International Journal of Nanomedicine2015ResearchNon-viral Gene Delivery
Jing Luo, Caixia Li, Jianlin Chen, Gang Wang, Rong Gao, Zhongwei Gu
Nonviral gene carriers (cationic polymers and lipids) are promising alternatives to viral vectors, but their transfection efficiencies are much lower. While extensive efforts have focused on chemical modification of gene delivery materials, simple optimisation of the transfection procedure itself—beyond standard…
Read the article →ACS Nano (Just Accepted Manuscript)2015ResearchNon-viral Gene Delivery
Jian Xiang, Ligeng Xu, Hua Gong, Wenwen Zhu, Chao Wang, Jun Xu, Liangzhu Feng, Liang Cheng, Rui Peng, Zhuang Liu
Dendritic cell (DC)-based immunotherapy requires efficient antigen delivery into DCs, DC maturation, and migration to draining lymph nodes, but real-time tracking of DC migration remains challenging with traditional methods (e.g., FITC painting). While upconversion nanoparticles (UCNPs) offer advantages for sensitive…
Read the article →Polymers for Advanced Technologies (Polym. Adv. Technol.)2014ResearchNon-viral Gene Delivery
Hongsuk Park, Joseph W. Nichols, Han Chang Kang, You Han Bae
Bioreducible polymers are attractive as gene carriers because they can reduce cytotoxicity compared with non-degradable cationic polymers such as polyethyleneimine (PEI). However, the safety and transfection efficiency of spermine-based bioreducible polyspermines had not been directly compared with linear PEI (lPEI)…
Read the article →Acta Biomaterialia2014ResearchNon-viral Gene Delivery
Corey J. Bishop, Stephany Y. Tzeng, Jordan J. Green
There is a need for improved nanobiotechnologies that enable intracellular delivery of difficult-to-deliver biologics such as nucleic acids. Ideally, a delivery material should deliver both large molecules such as DNA and small molecules such as siRNA—enabling both positive and negative regulation of genes—while…
Read the article →Journal of Controlled Release2014ResearchNon-viral Gene Delivery
Héloïse Ragelle, Raphaël Riva, Gaëlle Vandermeulen, Broes Naeye, Vincent Pourcelle, Cécile S. Le Duff, Cécile D’haese, Bernard Nysten, Kevin Braeckmans, Stefaan C. De Smedt, Christine Jérôme, Véronique Préat
Naked siRNA is unstable and inefficient, and chitosan-based carriers are limited by poor solubility at physiological pH and weak endosomal disruption. The study aimed to optimise chitosan nanoparticle formulations for intravenous siRNA delivery that achieve high gene silencing without cytotoxicity and remain stable…
Read the article →Bioconjugate Chemistry2014ResearchNon-viral Gene Delivery
Hauptmann N, Pion M, Wehner R, Muñoz-Fernández M-A, Schmitz M, Voit B, Appelhans D
Dendritic cell (DC)-based immunotherapy requires efficient delivery of antigens to immature DCs (iDCs) and maintenance of their immunostimulatory and migratory functions. Cationic PEI carriers are limited by dose-dependent toxicity and aggregation at endosomal pH, so a biocompatible, pH-responsive carrier is needed…
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