Nature Reviews Materials2017ReviewNon-viral Gene Delivery
Khalid A. Hajj And Kathryn A. Whitehead
mRNA therapeutics have enormous potential for vaccines, cancer immunotherapy, protein replacement, and gene editing, but widespread clinical application is limited by the lack of safe and effective delivery vehicles. Naked mRNA is large (~10⁵–10⁶ Da), densely negatively charged, and rapidly degraded by nucleases; its…
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 →Molecular Therapy — Methods & Clinical Development2016ReviewNon-viral Gene Delivery
Chen J, Guo Z, Tian H, Chen X.
Gene therapy is a promising strategy for treating gene-associated diseases, but clinical application is limited by inefficient delivery. Naked nucleic acids suffer from nuclease degradation, rapid renal clearance, phagocyte uptake, poor target-cell uptake, and immune-related toxicity. Nanoparticles are considered 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 →Macromolecular Bioscience2015ReviewNon-viral Gene Delivery
He, D.; Wagner, E
Polymeric gene delivery carriers such as PEI and poly(L-lysine) are heterogeneous and polydisperse, making site-specific multifunctional modification, structure–activity relationship studies, and reproducible clinical manufacturing difficult. This review argues that precisely defined polymeric materials — dendrimers…
Read the article →Journal of Controlled Release2015ReviewNon-viral Gene Delivery
Bishop, C. J.; Kozielski, K. L.; Green, J. J
Viral vectors raise safety concerns, and non-viral polymeric vectors still require optimisation for clinical translation. This review addresses how polymer structural features govern intracellular nucleic acid delivery — including cargo protection, cellular uptake, endosomal escape, unpacking, and nuclear delivery —…
Read the article →2015ReviewNon-viral Gene Delivery
Li, L.; Wei, Y.; Gong, C
Viral vectors are efficient but carry risks of immunogenicity, inflammatory reactions, recombination, limited DNA cargo capacity, and manufacturing difficulties. Non-viral polymeric vectors are safer and easier to produce, but their transfection efficiency remains much lower than viral vectors because of multiple…
Read the article →Journal of drug targeting2015ReviewNon-viral Gene Delivery
Kim J, Wilson Dr, Zamboni Cg, Green Jj
Cancer gene therapy requires safe and efficient delivery of nucleic acids, but viral vectors carry risks of immunogenicity and insertional tumorigenicity, while non-viral polymeric vectors are safer but less efficient. The review addresses the need for targeted polymeric nanoparticles that achieve tumour-specific…
Read the article →Chemical Reviews2015ReviewNon-viral Gene Delivery
Ulrich Lächelt And Ernst Wagner
Therapeutic nucleic acids—including plasmid DNA, mRNA, siRNA, miRNA, antisense oligonucleotides, and aptamers—have broad therapeutic potential, but their delivery to the correct intracellular site of action remains the dominant bottleneck. Polyplexes, formed by electrostatic complexation of nucleic acids with…
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…
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 →Nature Reviews Genetics2014ReviewNon-viral Gene Delivery
Yin H, Kanasty Rl, Eltoukhy Aa, Vegas Aj, Dorkin Jr, Anderson Dg.
Gene-based therapy has potential to treat a wide range of diseases, but clinical success is limited by delivery barriers. Viral vectors, while efficient, carry risks of carcinogenesis, immunogenicity, broad tropism, limited packaging capacity, and manufacturing difficulties. Non-viral vectors offer improved safety…
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 →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 →Journal of Drug Targeting (J Drug Target)2013ReviewNon-viral Gene Delivery
Jing Yao, Ying Fan, Yuanke Li, And Leaf Huang
Non-viral gene delivery systems are safer than viral vectors but are highly inefficient at nuclear delivery. Only ~10–20% of applied plasmid DNA enters targeted cells, and only ~1–5% of the applied dose reaches the nucleus. The nuclear envelope is a major barrier to transgene delivery, and there is a need for “smart”…
Read the article →Molecular Therapy.2013ReviewNon-viral Gene Delivery
El-Sayed A, Harashima H
Nonviral gene delivery vectors remain less efficient than viral vectors, and their intracellular fate is strongly influenced by the endocytic route they enter. The cell membrane is now understood to contain lipid raft and non-raft domains, and the initial binding domain can determine the primary endocytic vesicle…
Read the article →Journal of Controlled Release2013ReviewNon-viral Gene Delivery
Ragelle, H.; Vandermeulen, G.; Préat, V
Chitosan is attractive for siRNA delivery because it is cationic, biocompatible, biodegradable, mucoadhesive, and permeation-enhancing. However, native chitosan suffers from low solubility at physiological pH, poor buffering capacity, instability in biological fluids, and insufficient endosomal escape, limiting…
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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