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 →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…
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 →Materials2017ReviewNon-viral Gene Delivery
Sun, X.; Wu, G.; Xu, C.; Ye, Q.; Wang, C
Periodontitis causes irreversible destruction of periodontal tissues, and regeneration requires biomaterials with suitable mechanical, degradation, and biological properties. PLGA is attractive for periodontal regeneration because of its biocompatibility, tunable degradation, and processability, but its…
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 →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 →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 →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 →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 →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…
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 →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 →Nanoscale2014ReviewNon-viral Gene Delivery
Da Ma
siRNA-based gene therapy is a promising biotechnology for treating cancer and other diseases, but safe and efficient delivery is essential. Nanoparticle-mediated delivery must overcome multiple biological barriers, and endosomal escape is a critical rate-limiting barrier: nanoparticles are typically internalised via…
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 →European Journal of Pharmaceutics and Biopharmaceutics.2014ReviewNon-viral Gene Delivery
Slavomíra Doktorovová, Eliana B. Souto, Amélia Maria Silva
Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) were developed as alternative colloidal carriers with better stability and tolerability than polymeric nanoparticles. However, in vitro toxicity data were scattered across many cell lines, assays, exposure times, concentrations, and formulations…
Read the article →Pharmaceutics2013ReviewNon-viral Gene Delivery
Tam Yyc, Chen S, Cullis Pr
siRNA has broad therapeutic potential, but clinical translation is limited by rapid nuclease degradation, poor accumulation in target tissues, and inability to cross cell membranes to reach the cytoplasm. Lipid nanoparticles containing ionisable amino lipids are the leading systemic delivery system for siRNA, with…
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