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 →2014ResearchDrug Delivery
Lopes Rm, Gaspar Mm, Pereira J, Eleuterio Cv, Carvalho M, Almeida Aj, Cruz Mem
Current leishmaniasis chemotherapy lacks options that combine high activity, low toxicity, and affordable cost. Oryzalin (ORZ), a dinitroaniline with in vitro antileishmanial activity, is limited by poor water solubility and low accumulation in diseased organs. Lipid-based nanocarriers may overcome these limitations…
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 →Biochimica et Biophysica Acta (BBA) - Biomembranes2013ResearchNon-viral Gene Delivery
Fatemeh Madani, Rania Abdo, Staffan Lindberg, Hisaaki Hirose, Shiroh Futaki, Ulo Langel, Astrid Gräslund
Cell-penetrating peptides (CPPs) can internalise cells with biologically active cargo, but endosomal entrapment is a major limitation for cytoplasmic delivery, as cargo molecules must escape the endosome before degradation and acidification. While CPPs are known to enter cells via endocytosis, the background…
Read the article →The Journal of Immunology2013ResearchNon-viral Gene Delivery
Ying-Chun Lo, Michael A. Edidin, Jonathan D. Powell
Soluble anti-CD3 antibodies are potent T cell mitogens but activate all T cells regardless of TCR specificity, limiting their therapeutic utility for boosting antigen-specific responses. TCRs cluster into microclusters on the surface of antigen-experienced T cells but remain dispersed on naive T cells. This…
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…
Read the article →Advanced Healthcare Materials2013ResearchNon-viral Gene Delivery
Stephany Y. Tzeng, Jordan J. Green
Non-viral polymeric gene delivery to human brain cancer cells is often limited by low efficacy and poor understanding of how polymer structure should be tuned for different nucleic acid cargos. Glioblastoma has a poor prognosis, and improved delivery of DNA and siRNA could enable new therapies. DNA delivery: Leading…
Read the article →J. Phys. Chem. B2013ResearchNon-viral Gene Delivery
Tiia-Maaria Ketola, Martina Hanzlíková, Linda Leppänen, Manuela Raviña, Corey J. Bishop, Jordan J. Green, Arto O. Urtti, Helge J. Lemmetyinen, Marjo L. Yliperttula, Elina Vuorimaa
The structure–activity relationships governing polyplex formation by PEI and PLL are not well understood, especially whether DNA binding is independent or cooperative and how pH affects the mechanism. This limits rational design of nonviral gene delivery vectors. Polyplex core formation was complete at approximately…
Read the article →European Journal of Pharmaceutics and Biopharmaceutics2013ResearchNon-viral Gene Delivery
A.L. Silva, R.A. Rosalia, A. Sazak, M.G. Carstens, F. Ossendorp, J. Oostendorp, W. Jiskoot
Overlapping synthetic long peptides (SLPs) are promising for therapeutic cancer vaccination, but Montanide-based formulations have limitations including non-biodegradability, local side effects, poorly controlled release, and limited scalability. PLGA nanoparticles (NPs) offer a biodegradable alternative, but…
Read the article →2013ResearchNon-viral Gene Delivery
Tzeng, S. Y., Higgins, L. J., Pomper, M. G., & Green, J. J. (2013).
Liver cancer has limited curative options, and transarterial chemoembolization (TACE) provides local access for gene therapy. However, prior nonviral delivery strategies suffered from low in vitro efficacy and high toxicity to healthy liver cells. There is a need for a delivery platform that efficiently transfects…
Read the article →PNAS2012ResearchNon-viral Gene Delivery
David N. Nguyen, Kerry P. Mahon, Ghania Chikh, Phillip Kim, Hattie Chung, Alain P. Vicari, Kevin T. Love, Michael Goldberg, Steve Chen, Arthur M. Krieg, Jianzhu Chen, Robert Langer, Daniel G. Anderson
TLR7/8 agonists are promising vaccine adjuvants and antivirals, but RNA agonists are unstable and small-molecule agonists cause systemic toxicity. A delivery system specifically designed to deliver immunostimulatory RNA (isRNA) to TLR-expressing cells could enable safer and more localised innate immune activation. 14…
Read the article →Journal of Controlled Release2012ResearchNon-viral Gene Delivery
Hughes Ad, King Mr
Metastasis is the leading cause of cancer mortality, and circulating tumour cells (CTCs) are key to metastatic spread. Doxorubicin (DXR) is effective but systemically toxic and nonspecific. A targeted delivery system was needed to capture and kill CTCs under physiologically relevant flow while reducing off-target…
Read the article →Small2012ResearchNon-viral Gene Delivery
Nupura S. Bhise, Ron B. Shmueli, Jose Gonzalez, Jordan J. Green
Non-viral polymeric nanoparticles are promising for gene therapy and stem cell reprogramming, but the number of plasmids complexed per particle affects transfection efficiency and co-delivery of multiple plasmids. Existing methods for quantifying plasmids per particle have significant drawbacks, and few studies have…
Read the article →Journal of Controlled Release2012ResearchNon-viral Gene Delivery
Nianxi Zhao, Jianjun Qi, Zihua Zeng, Parag Parekh, Chung-Che Chang, Ching-Hsuan Tung, Youli Zu
Suspension lymphoma/leukemia cells are notoriously hard to transfect with non-viral vectors. Existing methods such as Lipofectamine give poor plasmid DNA delivery in these cells, and viral methods raise safety concerns. A simple, efficient, biodegradable cationic polymer nanocomplex is needed for gene delivery to…
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