Chemistry and Physics of Lipids2019ReviewNon-viral Gene Delivery
Scheideler M, Vidakovic I, Prassl R
miRNAs can regulate about 60% of protein-coding genes and enable targeting of previously “undruggable” proteins and diseases, but their clinical use is limited by nuclease degradation, poor tissue targeting, inefficient cellular uptake, and inadequate cytosolic release. Lipid nanocarriers are a versatile…
Read the article →Human Gene Therapy* (as indicated by article context and references)2018ReviewNon-viral Gene Delivery
Yao Xiao, Kun Shi, Ying Qu, Bingyang Chu, Zhiyong Qian
In the past 10 years, many clinical nano-gene therapy trials have been discontinued due to poor efficacy and serious side effects. There is a critical need to design suitable gene delivery systems that can protect nucleic acids, enhance transfection efficiency, penetrate deep into tumours, and remain stable and safe…
Read the article →Proceedings of the National Academy of Sciences (PNAS)2018ResearchNon-viral Gene Delivery
Ole A. W. Haabeth, Timothy R. Blake, Colin J. Mckinlay, Robert M. Waymouth, Paul A. Wender, Ronald Levy
mRNA-based cancer vaccination is a promising approach for personalised immunotherapy, but safe and effective mRNA delivery remains a major challenge due to mRNA's instability and poor cell membrane permeability. While lipid nanoparticles (LNPs) are the primary delivery strategy, they have limitations with respect to…
Read the article →PNAS2018ResearchNon-viral Gene Delivery
Colin J. Mckinlay, Nancy L. Benner, Ole A. Haabeth, Robert M. Waymouth, Paul A. Wender
Efficient mRNA delivery to lymphocytes remains a major unmet need for immunotherapy and vaccinology. Current methods rely largely on physical transfection such as electroporation, which is ex vivo, costly, and inefficient; chemical vectors generally achieve low lymphocyte mRNA transfection, especially in vivo. Lead…
Read the article →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 →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 →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 →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 →2017ReviewNon-viral Gene Delivery
Liposomes are attractive pharmaceutical carriers because they encapsulate hydrophilic and hydrophobic drugs and are biocompatible and biodegradable. However, conventional liposomes suffer from aggregation/fusion, premature payload release, rapid clearance by the mononuclear phagocyte system (MPS), low entrapment…
Read the article →International Journal of Pharmaceutics.2017ReviewNon-viral Gene Delivery
RNA interference (RNAi) therapeutics have shown potential for treating genetic, viral, and cancerous diseases, but the main bottleneck remains delivery of functional RNA molecules into the cell cytoplasm. The review focuses on liposomes and other lipid carriers, and on exosomes/extracellular vesicles (EVs), as…
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 →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 →Journal of Biomedical Nanotechnology2016ResearchNon-viral Gene Delivery
Stephen L. Hayward, David M. Francis, Parviz Kholmatov, Srivatsan Kidambi
miRNA-based therapeutics are limited by instability, poor cellular uptake, lack of targeting, and potential immune activation. No nonviral miRNA delivery strategy had been explored as a standalone treatment for HER2-positive metastatic breast cancer. HA-LNP uptake was significantly higher than naked FITC-dextran and…
Read the article →Drug Delivery2016ResearchDrug Delivery
Jie Qu, Liangqiao Zhang, Zhihua Chen, Guohua Mao, Ziyun Gao, Xianliang Lai, Xingen Zhu, Jianming Zhu
Glioblastoma multiforme (GBM) has a poor prognosis due to limited drug delivery across the blood–brain barrier (BBB), therapeutic resistance, and recurrence. Nanocarriers may improve temozolomide (TMZ) delivery, but it is unclear which nanocarrier type—polymeric nanoparticles (PNPs), solid lipid nanoparticles (SLNs)…
Read the article →Advanced Drug Delivery Reviews2016ReviewDrug Delivery
Niu Z, Conejos-Sánchez I, Griffin Bt, O’driscoll Cm, Alonso Mj
Peptide and protein therapeutics are highly potent but mostly require parenteral administration because they are degraded in the gastrointestinal tract, poorly permeate the intestinal epithelium, and have low oral bioavailability. Lipid-based nanocarriers are a promising strategy to enable oral peptide delivery by…
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 →Advanced Drug Delivery Reviews.2016ReviewNon-viral Gene Delivery
Cheng X, Lee Rj
Oligonucleotide (ON) therapeutics—antisense ONs, siRNA, miRNA mimics/inhibitors, antimiRs—are limited by poor membrane permeability, rapid renal/RES clearance, and nuclease degradation. LNPs can protect ONs and improve delivery, but the role of helper lipids in LNP stability, circulation, endosomal escape, and in…
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 →Journal of Controlled Release 200 (2015ResearchNon-viral Gene Delivery
H. Akita Et Al.
Cationic gene carriers can mediate cellular uptake but often show poor post-nuclear transcription/translation, toxicity, and aggregation in blood. The study aimed to develop a systemically applicable, tumour-targeting gene carrier that is neutral in blood/cytosol but becomes cationic in endosomes for endosomal…
Read the article →2015ReviewNon-viral Gene Delivery
Xue Hy, Guo P, Wen W-C, Wong Hl
RNAi therapeutics such as siRNA and miRNA can potently and specifically silence almost any gene, but systemic delivery is limited by poor cell permeation, rapid nuclease degradation, immunogenicity, and lack of target specificity. Lipid-based nanocarriers are among the most biocompatible and clinically advanced…
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…
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