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 →Journal of Controlled Release2018ResearchNon-viral Gene Delivery
Brynn R. Olden, Yilong Cheng, Jonathan L. Yu, Suzie H. Pun
CAR T cell immunotherapy requires efficient ex vivo gene delivery to primary human T cells, but viral vectors have limitations including cost, cargo size, insertional mutagenesis risk, and manufacturing complexity. Non-viral cationic polymers are attractive alternatives but historically show low gene transfer…
Read the article →International Journal of Pharmaceutics2018ResearchNon-viral Gene Delivery
Haimanti Mandal, Sameer S. Katiyar, Rajan Swami, Varun Kushwah, Parmeshwar B. Katare, Anand Kumar Meka, Sanjay K. Banerjee, Amirali Popat, Sanyog Jain
Non-viral gene delivery vectors are safer than viral vectors but often suffer from lower transfection efficiency and cytotoxicity. ε-Poly-L-lysine (ε-PLL) is a naturally occurring, FDA GRAS cationic polymer with low molecular weight and potential for low toxicity, but its use as a pDNA nanocarrier for efficient in…
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 →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 →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 →Nature Nanotechnology2017ResearchNon-viral Gene Delivery
Tyrel T. Smith, Sirkka B. Stephan, Howell F. Moffett, Laura E. Mcknight, Weihang Ji, Diana Reiman, Emmy Bonagofski, Martin E. Wohlfahrt, Smitha P. S. Pillai, Matthias T. Stephan
Adoptive T cell therapy with CAR-engineered T cells has shown impressive clinical results, but the ex vivo manufacturing process is complex, expensive, and requires specialised facilities, limiting widespread application. A method to programme circulating T cells directly in vivo with tumour-recognising capabilities…
Read the article →Theranostics2017ResearchNon-viral Gene Delivery
Xi Zhu, Wei Tao, Danny Liu, Jun Wu, Zilei Guo, Xiaoyuan Ji, Zameer Bharwani, Lili Zhao, Xiaoping Zhao, Omid C. Farokhzad, Jinjun Shi
Surface PEGylation of nanoparticles (NPs) improves circulation time and tumour accumulation but also hinders intracellular delivery, creating the "PEG dilemma" for siRNA therapeutics. While stimuli-responsive de-PEGylation strategies exist, they add complexity to NP design and synthesis. A tunable, serum…
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 →Materials Science and Engineering C2016ResearchNon-viral Gene Delivery
Maryam Hashemi, Seyed Meghdad Tabatabai, Hamideh Parhiz, Soroush Milanizadeh, Sara Amel Farzad, Khalil Abnous, Mohammad Ramezani
PAMAM and PPI dendrimers are widely investigated for gene delivery but suffer from limitations including cytotoxicity and inefficient endosomal escape. While both employ the proton sponge mechanism for endosomal release, higher generations that improve transfection also increase cytotoxicity. A systematic comparison…
Read the article →Journal of Biomedical Nanotechnology2016ResearchNon-viral Gene Delivery
Stephen L. Hayward, David M. Francis, Parviz Kholmatov, Srivatsan Kidambi
miRNA-based therapeutics are limited by instability, poor cellular uptake, lack of targeting, and potential immune activation. No nonviral miRNA delivery strategy had been explored as a standalone treatment for HER2-positive metastatic breast cancer. HA-LNP uptake was significantly higher than naked FITC-dextran and…
Read the article →Nanomedicine: Nanotechnology, Biology, and Medicine2016ResearchNon-viral Gene Delivery
Sara Palchetti, Daniela Pozzi, Cristina Marchini, Augusto Amici, Cristina Andreani, Caterina Bartolacci, Luca Digiacomo, Valentina Gambini, Francesco Cardarelli, Carmine Di Rienzo, Giovanna Peruzzi, Heinz Amenitsch, Rocco Palermo, Isabella Scrapanti, Giulio Caracciolo
Nonviral DNA delivery remains inefficient, and the barriers limiting transfection are incompletely understood. The study investigates multicomponent cationic liposome/DNA lipoplexes to identify an additional transfection barrier and improve delivery, especially in hard-to-transfect cells. MC cationic liposomes: 78.8…
Read the article →Journal of Controlled Release2016ResearchNon-viral Gene Delivery
Matthias Van Woensel, Nathalie Wauthoz, Rémi Rosière, Véronique Mathieu, Róbert Kiss, Florence Lefranc, Brecht Steelant, Ellen Dilissen, Stefaan W. Van Gool, Thomas Mathivet, Holger Gerhardt, Karim Amighi, Steven De Vleeschouwer
Galectin-1 (Gal-1) is overexpressed in glioblastoma multiforme (GBM), promotes tumour progression, angiogenesis, chemoresistance, and immune suppression. A non-invasive delivery strategy is needed to reach CNS tumours with siRNA while limiting systemic effects. The intranasal route was explored as an underexplored…
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 →Cell Chemical Biology (Chemistry & Biology)2015ResearchNon-viral Gene Delivery
Skye Zeller, Chang Seon Choi, Pradeep D. Uchil, Hong-Seok Ban, Alyssa Siefert, Tarek M. Fahmy, Walther Mothes, Sang-Kyung Lee, Priti Kumar
Arginine-rich cell-penetrating peptides (CPPs) such as nona-arginine (9R) can effectively translocate covalently attached biomolecules into cells, but poorly deliver electrostatically complexed siRNA, with most CPP:siRNA complexes trapped in endosomes. The mechanism by which ligand attachment to 9R overcomes this…
Read the article →International Journal of Nanomedicine2015ResearchNon-viral Gene Delivery
Zhenyu Shao, Jingyu Shao, Bingxu Tan, Shanghai Guan, Zhulong Liu, Zengjun Zhao, Fangfang He, Jian Zhao
Lung cancer chemotherapy is limited by multidrug resistance, severe adverse effects, and poor tumour targeting. A nanocarrier that actively targets lung cancer cells and co-delivers a cytotoxic drug plus therapeutic DNA could improve efficacy and reduce off-target toxicity. Tf₅ₖ-PTX-DNA-NLC: ~133 nm, zeta +19 mV…
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 →Cancer Biology & Therapy2014ResearchNon-viral Gene Delivery
Paulina Wyrozumska, Justyna Meissner, Monika Toporkiewicz, Marta Szarawarska, Kazimierz Kuliczkowski, Maciej Ugorski, Marta A. Walasek & Aleksander F. Sikorski
Most cancer gene therapy research has focused on solid tumours, while blood cancers such as leukaemia and lymphoma have received less attention. There is a need for a lipid carrier that protects antisense oligonucleotides or plasmid DNA from enzymatic degradation, is stable in serum, has low toxicity, and can…
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 →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…
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