Molecular Therapy2017ReviewNon-viral Gene Delivery
Cullis Pr, Hope Mj
Genetic drugs such as siRNA, mRNA, and plasmid DNA could treat most diseases by silencing pathological genes, expressing therapeutic proteins, or enabling gene editing. However, naked RNA/DNA is rapidly degraded, does not accumulate in target tissues, and cannot cross cell membranes efficiently. Lipid nanoparticles…
Read the article →Gene Therapy2017ReviewNon-viral Gene Delivery
Zylberberg C, Gaskill K, Pasley S, Matosevic S
Liposome-mediated gene delivery faces systemic barriers, endosomal escape, lysosomal degradation, and nuclear uptake limitations, while interactions between lipid nanoparticles and cells remain poorly understood. Rational design of targeted liposomes is needed to reduce off-target effects and enhance transfection…
Read the article →Journal of Controlled Release2016ReviewNon-viral Gene Delivery
Kevin J. Kauffman, Matthew J. Webber, Daniel G. Anderson
mRNA therapeutics have broad potential for protein replacement therapy, cancer immunotherapy, and genomic engineering, but effective intracellular delivery remains a major challenge. A chemically diverse suite of delivery materials—originally developed for DNA and siRNA transfection—has recently shown promise for…
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 →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 →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 →2016ReviewDrug Delivery
Rizwanullah M, Ahmad J, Amin S
Conventional cancer chemotherapy suffers from poor drug specificity, narrow therapeutic windows, high dose-limiting toxicity, and multidrug resistance (MDR). Nanostructured lipid carriers (NLCs) are biocompatible, biodegradable lipid-based nanoparticles that can improve solubility, stability, targeting, and…
Read the article →Nature2016ReviewNon-viral Gene Delivery
Green, J. J.; Elisseeff, J. H
Biomaterials must increasingly do more than simply avoid rejection; they must actively mimic biological structures and functions to direct cell behaviour, modulate immunity, and repair tissues. This review addresses how biologically inspired polymers can be designed for local tissue engineering, systemic therapeutic…
Read the article →Advanced Drug Delivery Reviews2016ReviewNon-viral Gene Delivery
Suk, J. S.; Xu, Q.; Kim, N.; Hanes, J.; Ensign, L. M
PEGylation is widely used to improve nanoparticle drug and gene delivery by reducing aggregation, opsonisation, and phagocytic clearance, thereby prolonging circulation. However, the field lacks a consolidated understanding of how PEG molecular weight, surface density, conformation, core properties, administration…
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 →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 →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 →Journal of Controlled Release.2015ReviewNon-viral Gene Delivery
De Jesus Mb, Zuhorn Is
Non-viral nucleic acid delivery requires carriers that protect DNA/RNA from nucleases and facilitate intracellular delivery. Solid lipid nanoparticles (SLNs) are promising, but the molecular mechanisms by which they assemble with nucleic acids, transfect cells, and release cargo remain poorly understood compared with…
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 →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 →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 →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…
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