Biomaterials2017ResearchNon-viral Gene Delivery
Shi Gn, Zhang Cn, Xu R, Niu Jf, Song Hj, Zhang Xy, Wang Ww, Wang Ym, Li C, Wei Xq, Kong Dl
Whole tumour cell lysates (TCL) are a broad source of tumour antigens for cancer vaccines, but soluble TCL is unstable, poorly taken up by dendritic cells (DCs), and inefficient at inducing cytotoxic T lymphocyte (CTL) responses. A delivery system was needed to protect TCL antigens, target DCs, and enhance antigen…
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 →Drug Delivery2016ResearchDrug Delivery
Jie Qu, Liangqiao Zhang, Zhihua Chen, Guohua Mao, Ziyun Gao, Xianliang Lai, Xingen Zhu, Jianming Zhu
Glioblastoma multiforme (GBM) has a poor prognosis due to limited drug delivery across the blood–brain barrier (BBB), therapeutic resistance, and recurrence. Nanocarriers may improve temozolomide (TMZ) delivery, but it is unclear which nanocarrier type—polymeric nanoparticles (PNPs), solid lipid nanoparticles (SLNs)…
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 →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 →Proceedings of the National Academy of Sciences (PNAS)2015ResearchNon-viral Gene Delivery
Tim Willinger, Matthew Staron, Shawn M. Ferguson, Pietro De Camilli, Richard A. Flavell
Prolonged T-cell receptor (TCR) signalling is required for T lymphocyte proliferation, yet TCR ligation paradoxically causes internalisation and down-modulation of the TCR from the cell surface. It is unknown how TCR signalling is sustained for many hours despite lower surface expression. Understanding whether TCR…
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 →Biomaterials2014ResearchNon-viral Gene Delivery
Luis J. Cruz, Rodney A. Rosalia, Jan Willem Kleinovink, Felix Rueda, Clemens W.G.M. Löwik, Ferry Ossendorp
Dendritic cell (DC)-based therapies have shown clinical benefits but are hampered by labour-intensive, GMP-regulated vaccine preparations requiring multiple steps and donor variability. In vivo targeting of antigens to DC surface receptors using nanoparticle delivery systems could circumvent these drawbacks. However…
Read the article →Nature Nanotechnology2014ResearchNon-viral Gene Delivery
Tarek R. Fadel, Fiona A. Sharp, Nalini Vudattu, Ragy Ragheb, Justin Garyu, Dongin Kim, Enping Hong, Nan Li, Gary L. Haller, Lisa D. Pfefferle, Sune Justesen, Kevan C. Herold, Tarek M. Fahmy
Adoptive cell transfer of tumour-specific T cells is a promising cancer immunotherapy, but efficient and economical ex vivo expansion of T cells remains a bottleneck. Artificial antigen-presenting cells (aAPCs) with high surface area and modular design could overcome cost and scalability limits of dendritic…
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 →BMC Immunology2014ResearchNon-viral Gene Delivery
Kyung Hee Noh, Yeong Min Park, Hyuk Soon Kim, Tae Heung Kang, Kwon‐ho Song, Young‐ho Lee, Yeongseon Byeon, Hat Nim Jeon, In Duk Jung, Byung Cheol Shin, Kyung‐mi Lee, Seung‐yong Seong, Hee Dong Han, Tae Woo Kim
Conventional adjuvants such as Complete Freund’s Adjuvant (CFA) and Incomplete Freund’s Adjuvant (IFA) are potent but toxic, limiting clinical use. A safer, biodegradable adjuvant system was needed to enhance antigen-specific humoral and cellular immunity without severe local or systemic side effects. Safety: CH-HG…
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…
Read the article →Pharmaceutical Development and Technology (Informa Healthcare)2014ResearchNon-viral Gene Delivery
Jaber Emami, Aida Pourmashhadi, Hojat Sadeghi, Jaleh Varshosaz, Hamed Hamishehkar
COX-2 is overexpressed in non-small cell lung cancer (NSCLC) and is associated with poor prognosis. Celecoxib (Cxb), a COX-2 inhibitor, has antiproliferative and proapoptotic effects, but systemic administration carries cardiovascular risks. Pulmonary inhalation delivery of Cxb encapsulated in biodegradable PLGA…
Read the article →Cellular Immunology (Elsevier)2014ResearchNon-viral Gene Delivery
Mingshui Chen, Haichao Ouyang, Shangyong Zhou, Jieyu Li, Yunbin Ye
Agonistic anti-OX40 monoclonal antibody (mAb) can enhance anti-tumour immunity in preclinical models, but as monotherapy it showed only marginal activity and no objective clinical responses in a phase I trial. A delivery system that improves T cell access, multivalent OX40 engagement, and sustained release of…
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 →PLOS ONE2013ResearchNon-viral Gene Delivery
Lais Chayabam, Aline Laino Sodre, Bruno A. Curzio, Martin H. Bonamino
Genetic modification of T lymphocytes is essential for both basic research and immunotherapy (e.g., CAR-T cell generation), but existing methods rely on expensive commercial electroporation kits (Lonza Nucleofector® kits) or time-consuming viral vector production. The high cost and dependence on proprietary reagents…
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…
Read the article →Biotechnology and Bioengineering, Vol. 110, No. 3, March2013ResearchNon-viral Gene Delivery
Branching architecture is a tunable parameter for polymeric gene carriers, but how the degree of branching (DB) of bioreducible poly(amido amine)s (PAAs) affects pDNA binding, cellular uptake, endocytosis pathways, and transfection efficiency was not well defined. pDNA condensation: HBPAA completely retarded pDNA at…
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