European Journal of Medicinal Chemistry2022ReviewNon-viral Gene Delivery
Mingyuan Li, Yuan Li, Shiqin Li, Lin Jia, Haomeng Wang, Meng Li, Jie Deng, Ali Zhu, Liqiao Ma, Weihong Li, Peng Yu, And Tao Zhu
The COVID-19 pandemic has greatly accelerated the application of mRNA technology, demonstrating its unique advantages over traditional biopharmaceutical and vaccine technology. However, mRNA instability in human physiological environments and inefficient in vivo delivery remain major barriers. mRNA chemical…
Read the article →Advanced Healthcare Materials2021ReviewNon-viral Gene Delivery
Ho W, Gao M, Li F, Li Z, Zhang X-Q, Xu X.
Nucleic acid vaccines (DNA and mRNA) offer rapid design, adaptability to changing pathogen strains, and stimulation of both humoral and cellular immunity, but their clinical translation is limited by inefficient delivery—nucleic acids are rapidly degraded by endogenous nucleases, have poor cellular uptake due to…
Read the article →International Immunopharmacology2020ReviewNon-viral Gene Delivery
Hashemi V, Farhadi S, Ghasemi Chaleshtari M, Et Al.
Dendritic cell (DC)-based cancer immunotherapy has shown impressive outcomes, including the first FDA-approved anti-cancer vaccine, but clinical application faces challenges such as limited durable responses, antigen selection issues, and immunosuppressive tumour microenvironments. Nanoparticles (NPs) are promising…
Read the article →International Journal of Nanomedicine2020ReviewNon-viral Gene Delivery
Chen, C.-K.; Huang, P.-K.; Law, W.-C.; Chu, C.-H.; Chen, N.-T.; Lo, L.-W
Gene therapy is limited by the fragile nature of therapeutic DNA/RNA and by safety concerns with viral vectors. Non-viral polymeric vectors are attractive, but conventional cationic polymers such as PEI, PDMAEMA, and PLL are often non-degradable, causing accumulation, cytotoxicity, and poor gene unpacking. This…
Read the article →Biochimie2019ReviewDrug Delivery
Aqeel Ahmad, Javed Masood Khan, Shafiul Haque
Endosomal escape remains the rate-limiting step for efficient gene and drug delivery using nanoparticles (NPs). Despite continuous advancements, most NPs internalised via endocytic pathways are degraded by hydrolytic enzymes in lysosomes, severely limiting therapeutic efficacy. There is an unmet need to…
Read the article →Pharmaceutics (MDPI)2019ReviewNon-viral Gene Delivery
Run Ni, Ruoyu Fang, And Ying Chau
While many reviews have systematically covered different types of formulation materials for gene delivery, a parallel comparison of different formulation materials together with an analysis of the correlation between their material properties and nucleic acid delivery functions has not been conducted. Understanding…
Read the article →Journal of Controlled Release2019ReviewNon-viral Gene Delivery
Cordeiro, R. A.; Serra, A.; Coelho, J. F. J.; Faneca, H
Gene therapy requires safe and effective delivery vectors. PBAEs are biodegradable cationic polymers with excellent gene delivery properties, but a comprehensive and critical overview of their use as gene carriers is lacking. This review provides the first comprehensive and critical overview of PBAE-based gene…
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 →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 →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 →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 →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 →Chemical Society Reviews2012ReviewDrug Delivery
Samal, S. K.; Dash, M.; Van Vlierberghe, S.; Kaplan, D. L.; Chiellini, E.; Van Blitterswijk, C.; Moroni, L.; Dubruel, P
Cationic polymers are widely studied as non-viral gene delivery vectors, but their therapeutic potential extends well beyond gene delivery. This review addresses the need for a broader overview of cationic polymers — their synthesis, modification, bioactive properties, architectures, and applications in drug…
Read the article →2011ReviewNon-viral Gene Delivery
Chou Lyt, Ming K, Chan Wcw.
Nanoparticles (NPs) are increasingly used as contrast agents, therapeutics, and delivery vehicles, but their effective delivery into cells and to specific subcellular organelles remains a major challenge. The review addresses fundamental barriers to intracellular NP delivery—plasma membrane, endosomal entrapment…
Read the article →2011ReviewNon-viral Gene Delivery
Kim, T.-I.; Kim, S. W
Bioreducible polymers containing disulfide linkages are attractive gene-delivery carriers because they are stable in the oxidizing extracellular environment but degrade rapidly in the reducing intracellular cytosol via thiol–disulfide exchange, triggered by high glutathione (GSH) levels. This review addresses the…
Read the article →Soft Matter2010ReviewNon-viral Gene Delivery
Parhamifar, L.; Larsen, A. K.; Hunter, A. C.; Andresen, T. L.; Moghimi, S. M
Efficient transfection with low toxicity is essential for nucleic acid therapeutics, but synthetic polycations such as polyethylenimine (PEI) are limited by cytotoxicity. This review critically assesses the safety and efficacy challenges of PEI-based polyplexes, identifies deficiencies in the field, and proposes…
Read the article →European Journal of Pharmaceutical Sciences2010ReviewNon-viral Gene Delivery
Conchita Tros De Ilarduya, Yan Sun, Nejat Düzgüneş
Viral vectors achieve high gene transfer efficiency but can induce immune/inflammatory responses, have limited DNA carrying capacity, and raise recombination and cost concerns. Non-viral vectors such as cationic lipids and polymers are safer alternatives, but their transfection efficiency—especially in vivo—remains…
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