Annual Review of Chemical and Biomolecular Engineering2018ReviewNon-viral Gene Delivery
Karlsson, J.; Vaughan, H. J.; Green, J. J
Biodegradable polymeric nanoparticles have great potential to improve cancer therapy by enabling targeted delivery, triggered release, and reduced off-target toxicity. This review addresses how such nanocarriers can be engineered to overcome systemic, organ-level, and cellular barriers and to target cancer cells…
Read the article →Current Opinion in Biomedical Engineering2018ReviewNon-viral Gene Delivery
Tzeng Sy, Green Jj
Nucleic acids can be used to engineer the immune system, but their clinical use requires better specificity and intracellular delivery efficiency. Viral vectors have manufacturing, cargo-capacity, safety, and immunological drawbacks; therefore, polymers are being developed as non-viral delivery vehicles whose…
Read the article →Frontiers in Pharmacology2018ReviewDrug Delivery
Sima Rezvantalab, Natascha Ingrid Drude, Mostafa Keshavarz Moraveji, Nihan Güvener, Emily Kate Koons, Yang Shi, Twan Lammers, Fabian Kiessling
PLGA-based nanoparticles are widely investigated for cancer therapy, but their clinical translation remains limited. A consolidated overview was needed of how PLGA NP physicochemical properties, biological behaviour, targeting strategies, and combination therapies interact—and why promising preclinical results have…
Read the article →Theranostics2017ReviewNon-viral Gene Delivery
Chao Wang, Wujin Sun, Yanqi Ye, Hunter N. Bomba, Zhen Gu
Immune cell/organ therapies based on manipulation, infusion, and implantation of autologous or allogeneic cells/organs are costly, time-consuming, and sometimes limited in clinical effectiveness. Biomimetic materials and strategies offer an alternative by enabling artificial immune cells and lymphoid organs that are…
Read the article →Chemical Society Reviews2017ReviewNon-viral Gene Delivery
Shahed Behzadi, Vahid Serpooshan, Wei Tao, Majd A. Hamaly, Mahmoud Y. Alkawareek, Erik C. Dreaden, Dennis Brown, Alaaldin M. Alkilany, Omid C. Farokhzad, Morteza Mahmoudi
Nanoparticles (NPs) are increasingly used in consumer goods, electronics, and pharmaceuticals, but their beneficial and/or deleterious effects ultimately arise from interactions at the cellular and subcellular level. While many NPs require safe entry into cells for therapeutic efficacy, efficient and controlled…
Read the article →Bioscience Reports2017ReviewNon-viral Gene Delivery
Haiqing Bai, Gillian M. Schiralli Lester, Laura C. Petishnok, David A. Dean
Productive gene transfer requires plasmid DNA to not only enter cells but also traffic through the cytoplasm and cross the nuclear envelope. Most transfection strategies focus on membrane entry and promoter choice, but cytoplasmic trafficking and nuclear import are critical, rate-limiting barriers—especially because…
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 →Nature Communications2017ResearchNon-viral Gene Delivery
Daniela Schmid, Chun Gwon Park, Christina A. Hartl, Nikita Subedi, Adam N. Cartwright, Regina Bou Puerto, Yiran Zheng, James Maiarana, Gordon J. Freeman, Kai W. Wucherpfennig, Darrell J. Irvine, Michael S. Goldberg
Systemic immune stimulation for cancer immunotherapy is associated with autoimmune-type pathologies, as the doses required to break immune tolerance can invoke undesired host-vs.-host effects. Targeting endogenous immune cell subsets in the circulation—which actively migrate into tumours—could concentrate…
Read the article →2017ResearchNon-viral Gene Delivery
Petra Furedi, Zsofia Edit Papay, Kristof Kovacs, Borbala Dalmadi Kiss, Krisztina Ludanyi, Istvan Antal, Imre Klebovich
Topical fungal infections, including ocular mycoses, are increasing, and voriconazole (VCZ) is an effective antifungal but has poor water solubility, limiting liquid ophthalmic formulations. Lipid-based nanoparticles (LNPs/SLNs) may improve VCZ solubility, loading, and topical delivery. Optimised formulation (SLN2)…
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 →Biomaterials2017ResearchNon-viral Gene Delivery
Yoshizaki Y, Yuba E, Sakaguchi N, Koiwai K, Harada A, Kono K
Efficient cancer vaccine carriers need both antigen delivery to dendritic cells (DCs) and DC activation. Previous pH-sensitive polymer-modified liposomes delivered antigen to DC cytosol but had limited adjuvant potency, and combining cationic lipid TRX with MPLA reduced antitumor effects, suggesting a need for…
Read the article →International Journal of Pharmaceutics2017ResearchNon-viral Gene Delivery
Genada Sinani, Melike Sessevmez, M. Koray Gök, Saadet Özgümüş, Alper Okyar, H. Oya Alpar, Erdal Cevher
Mucosal vaccination can stimulate both mucosal and systemic immunity, but free protein antigens generally induce poor systemic immune responses and require adjuvants. There is a need for a safe, effective nasal vaccine carrier that improves antigen stability, uptake, and immunogenicity, especially for poorly…
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 →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 →2017ReviewNon-viral Gene Delivery
Jiménez Blanco Jl, Benito Jm, Ortiz Mellet C, García Fernández Jm.
Nonviral gene delivery lacks molecularly well-defined carriers suitable for rigorous structure–activity relationship (SAR) studies. Viral vectors raise immunogenicity, cost, and cargo-size concerns, while polymers, dendrimers, and cationic lipids are often polydisperse or supramolecularly ill-defined. The review…
Read the article →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 →Frontiers in Immunology.2017ReviewDrug Delivery
Mizrahy S, Hazan-Halevy I, Landesman-Milo D, Ng Bd, Peer D
Current cancer immunotherapy shows promise but fails across many tumour types, likely because single-pathway treatments cannot overcome the complex immunosuppressive tumour microenvironment (TME). Lipid-based nanoparticles (LNPs) may allow simultaneous, temporally coordinated delivery of multiple immune modulators to…
Read the article →Journal of Controlled Release.2017ReviewNon-viral Gene Delivery
Tapeinos C, Battaglini M, Ciofani G
Delivery of therapeutics to the CNS is severely limited by the blood–brain barrier (BBB). Polymeric and inorganic nanoparticles have shown utility but face toxicity, scalability, and organic-solvent concerns. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are biocompatible lipid-based…
Read the article →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…
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