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 →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 →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 →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 →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 →Polymers for Advanced Technologies (Polym. Adv. Technol.)2014ResearchNon-viral Gene Delivery
Hongsuk Park, Joseph W. Nichols, Han Chang Kang, You Han Bae
Bioreducible polymers are attractive as gene carriers because they can reduce cytotoxicity compared with non-degradable cationic polymers such as polyethyleneimine (PEI). However, the safety and transfection efficiency of spermine-based bioreducible polyspermines had not been directly compared with linear PEI (lPEI)…
Read the article →Biochimica et Biophysica Acta (BBA) - Biomembranes2013ResearchNon-viral Gene Delivery
Fatemeh Madani, Rania Abdo, Staffan Lindberg, Hisaaki Hirose, Shiroh Futaki, Ulo Langel, Astrid Gräslund
Cell-penetrating peptides (CPPs) can internalise cells with biologically active cargo, but endosomal entrapment is a major limitation for cytoplasmic delivery, as cargo molecules must escape the endosome before degradation and acidification. While CPPs are known to enter cells via endocytosis, the background…
Read the article →ACS Applied Materials & Interfaces (Just Accepted Manuscript)2013ResearchNon-viral Gene Delivery
Cuicui Li, Stephany Y. Tzeng, Liane E. Tellier, Jordan J. Green
DNA-based therapeutics require an intracellular delivery system to be effective. For diseases like brain cancer—where local access to residual tumour is often available following surgical resection—an implantable device that enables both controlled release and intracellular delivery of DNA could open new…
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 →2012ReviewNon-viral Gene Delivery
Zhang X-X, Mcintosh Tj, Grinstaff Mw
Cationic lipids are the most common non-viral gene-delivery vectors, but they generally suffer from low transfection efficiency. Functional or stimulus-responsive lipids—especially pH-, redox-, and charge-reversal-sensitive lipids—may improve nucleic acid delivery by enabling triggered cargo release, endosomal…
Read the article →Journal of Controlled Release2011ResearchNon-viral Gene Delivery
Tae-Il Kim, Thomas Rothmund, Thomas Kissel, Sung Wan Kim
Endosomal escape remains a major barrier for polymeric gene delivery. Arginine-grafted bioreducible polymers (ABPs) show high transfection via cell-penetrating arginine, but the effect of adding endosome-buffering moieties on their biophysical and transfection properties was not well defined. Buffering capacity…
Read the article →Biomaterials2011ResearchNon-viral Gene Delivery
Dai J, Zou S, Pei Y, Cheng D, Ai H, Shuai X
PEI is an effective gene carrier but high-molecular-weight PEI is nonbiodegradable and cytotoxic; PLL is biodegradable but lacks proton-buffering capacity, has low transfection efficiency, and is also cytotoxic. A vector combining the complementary strengths of PEI and PLL is needed. Cytotoxicity: At 100 µg/mL, PPL…
Read the article →Journal of Controlled Release2011ResearchNon-viral Gene Delivery
Yanan Yue, Fan Jin, Rui Deng, Jinge Cai, Zhuojun Dai, Marie C.M. Lin, Hsiang‐fu Kung, Maria Ahlm Mattebjerg, Thomas Lars Andresen, Chi Chung Wu
PEI is one of the best nonviral gene delivery vectors, but why it works so well remains unclear. In particular, the role of free, uncomplexed PEI chains and their length in transfection, cellular uptake, and endosomal escape has not been quantitatively resolved, and the “proton sponge” mechanism is increasingly…
Read the article →Biomaterials2011ResearchNon-viral Gene Delivery
Stephany Y. Tzeng, Hugo Guerrero‐cazares, Elliott E. Martinez, Joel C. Sunshine, Alfredo Quiñones‐hinojosa, Jordan J. Green
Glioblastoma (GB) has poor survival and current therapies are insufficient. Viral gene therapy carries safety risks, while nonviral vectors often lack efficiency and practical storage stability. PBAEs had shown high transfection and low toxicity in other cell types but had not been tested in primary brain tumour…
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 →Journal of Drug Delivery2011ReviewNon-viral Gene Delivery
Daniel A. Balazs, W.T. Godbey
Liposomes are versatile, biocompatible vesicular carriers that can encapsulate and deliver DNA or RNA, but the relationship between lipid charge, lipid packing, and gene-delivery efficiency remains complex. This review discusses physical packing parameters and specific lipids used for gene delivery, classified by…
Read the article →2010ResearchNon-viral Gene Delivery
Kai K. Ewert, Alexandra Zidovska, Ayesha Ahmad, Nathan F. Bouxsein, Heather M. Evans, Christopher S. Mcallister, Charles E. Samuel, Cyrus R. Safinya
Cationic lipid–nucleic acid (CL-NA) complexes are promising non-viral vectors for gene delivery and siRNA-mediated silencing, but their transfection and silencing efficiencies remain low compared with viral vectors. A major gap is poor mechanistic understanding of how complex structure, membrane charge density, and…
Read the article →International Journal of Pharmaceutics2010ResearchNon-viral Gene Delivery
Zhang Y, Li H, Sun J, Gao J, Liu W, Li B, Guo Y, Chen J
DC-Chol/DOPE cationic liposomes are efficient non-viral vectors, but the effects of DC-Chol/DOPE molar ratio, PEGylation, and serum on pDNA versus siRNA delivery were unclear. The study also aimed to test whether pDNA and siRNA have different transfection mechanisms in these liposomes. Optimal DC-Chol/DOPE molar…
Read the article →Biomaterials2010ResearchNon-viral Gene Delivery
Nupura S. Bhise, Ryan S. Gray, Joel C. Sunshine, Soe Htet, Andrew J. Ewald, Jordan J. Green
Non-viral gene delivery vectors are safer alternatives to viral vectors but often suffer from low transfection efficiency, especially in hard-to-transfect primary cells and 3-D tissue models. There is a need to understand how small changes in polymer structure—specifically terminal functionalisation and molecular…
Read the article →Journal of Internal Medicine2010ReviewNon-viral Gene Delivery
Schroeder A, Levins Cg, Cortez C, Langer R, Anderson Dg
RNAi has strong therapeutic potential, but clinical translation of siRNA is limited by delivery. siRNA is large, negatively charged, susceptible to nuclease degradation, poorly taken up by cells, and must reach the cytoplasm to engage RISC. Safe and effective lipid-based delivery systems are needed to protect siRNA…
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…
Read the article →2009ReviewNon-viral Gene Delivery
Sunshine, J.; Bhise, N.; Green, J. J
Non-viral gene delivery needs safe and effective carriers. PEI is effective but cytotoxic, while viral vectors raise safety concerns. Degradable poly(β-amino ester)s may provide effective gene delivery with reduced cytotoxicity. This study investigates how small changes in polymer synthesis ratio and end-group…
Read the article →International Journal of Pharmaceutics2008ResearchNon-viral Gene Delivery
Yongxin Yang, Zhenghong Xu, Shangwei Chen, Yu Gao, Wangwen Gu, Lingli Chen, Yuanying Pei, Yaping Li
Cationic polymers are widely studied non-viral gene vectors but generally show lower transfection efficiency than viral vectors. Endosomal escape is a major bottleneck. Histidine/imidazole-containing polymers can enhance gene expression via a “proton sponge” effect without increasing toxicity. Polyphosphazenes are…
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