Small Methods.2018ReviewNon-viral Gene Delivery
Evers Mjw, Kulkarni Ja, Van Der Meel R, Cullis Pr, Vader P, Schiffelers Rm
Free siRNA, mRNA, pDNA, and CRISPR/Cas9 components are rapidly degraded and cleared, so delivery systems are required. LNPs are the most clinically advanced non-viral siRNA carriers; Patisiran reached Phase III and market application in late 2017. The field needed a clearer understanding of LNP design parameters and…
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 →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 →WIREs Nanomedicine and Nanobiotechnology2017ReviewNon-viral Gene Delivery
Selby, L. I.; Cortez-Jugo, C. M.; Such, G. K.; Johnston, A. P. R
Endosomal escape is widely considered the rate-limiting bottleneck for cytoplasmic delivery of nucleic acids, proteins, and other therapeutics using polymeric and lipid nanoparticles. The field lacks robust methods to quantify escape efficiency and understand its mechanisms, limiting rational design of improved…
Read the article →Advanced Drug Delivery Reviews2016ReviewNon-viral Gene Delivery
Jayoung Kim, Adam C. Mirando, Aleksander S. Popel, Jordan J. Green
Angiogenesis is normally balanced by pro- and anti-angiogenic factors, but imbalance leads to aberrant angiogenesis in ischaemia, tissue regeneration, cancer, and neovascular age-related macular degeneration (wet AMD). Gene therapy is a promising strategy to introduce exogenous nucleic acids that express or silence…
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 →Advanced Drug Delivery Reviews2015ReviewNon-viral Gene Delivery
Yunching Chen, Dong-Yu Gao, Leaf Huang
miRNAs can simultaneously regulate multiple cancer-related genes, making them attractive therapeutic agents or targets. However, efficient, specific, and safe systemic delivery of therapeutic miRNAs in vivo remains a major challenge due to rapid degradation, poor tumour penetration, immunotoxicity, endosomal…
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 →BioMed Research International.2014ReviewNon-viral Gene Delivery
Torrecilla J, Rodríguez-Gascón A, Solinís Má, Del Pozo-Rodríguez A
Naked RNAi molecules are rapidly degraded by serum nucleases and cannot readily cross cell membranes because of their negative charge. Effective delivery systems are therefore required to exploit RNAi for antiviral therapy. Lipid nanoparticles (LNPs) are attractive because they are relatively safe, simple to produce…
Read the article →Pharmazie.2011ReviewNon-viral Gene Delivery
Cationic liposomes (CLs) are attractive non-viral gene-delivery carriers because they are safer, less immunogenic, and easier to prepare than viral vectors, but their transfection efficiency (TE) remains low and the relationship between lipoplex physicochemical properties, lipoplex–cell interaction, and TE is poorly…
Read the article →British Journal of Pharmacology2009ReviewNon-viral Gene Delivery
Midoux P, Pichon C, Yaouanc J-J, Jaffrès P-A
Non-viral nucleic acid delivery systems—lipoplexes, polyplexes, and lipopolyplexes—are limited mainly by poor endosomal escape. The review examines whether histidine- and imidazole-containing carriers can exploit the acidic endosomal environment to destabilize membranes and improve cytosolic delivery of DNA, mRNA…
Read the article →1989ReviewNon-viral Gene Delivery
Felgner Pl, Ringold Gm
Existing polynucleotide delivery methods—calcium phosphate, DEAE-dextran, electroporation, retroviral vectors—had limitations in convenience, reproducibility, efficiency, and applicability across cell types. A simple, broadly effective cationic liposome reagent was needed for DNA and RNA transfection of mammalian…
Read the article →ReviewNon-viral Gene Delivery
The transferrin receptor (TfR) is overexpressed on many cancer cells and is efficiently internalised, making it a useful target for delivering small-molecule drugs and nucleic acid therapeutics while reducing non-target effects. The review summarises TfR biology, Tf-lipoplex development, and therapeutic applications…
Read the article →