Proceedings of the National Academy of Sciences of the United States of America (PNAS)2010ResearchNon-viral Gene Delivery
Fan Yang, Seung-Woo Cho, Sun Mi Son, Said R. Bogatyrev, Deepika Singh, Jordan J. Green, Ying Mei, Sohyun Park, Suk Ho Bhang, Byung-Soo Kim, Robert Langer, Daniel G. Anderson
Stem cell therapy for angiogenesis is limited by insufficient expression of angiogenic factors and poor cell viability after transplantation. Viral gene delivery raises safety concerns, while non-viral methods often suffer from low transfection efficiency and toxicity. A safe, efficient, biodegradable polymeric…
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 →Gene Therapy2010ReviewNon-viral Gene Delivery
Lam Ap, Dean Da.
The nuclear envelope remains a major barrier to successful nonviral transfection and gene therapy. After exogenous DNA is delivered to the cytoplasm, it rapidly complexes with cellular proteins that control its intracellular trafficking and nuclear import. Understanding these mechanisms is necessary to improve…
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…
Read the article →Expert Opinion on Drug Delivery2010ReviewNon-viral Gene Delivery
Zhu L, Mahato Ri
Nucleic acid therapeutics—plasmid DNA, antisense oligonucleotides, and RNAi molecules—have broad therapeutic potential but face major biological barriers, including nuclease degradation, poor membrane penetration, endosomal entrapment, nonspecific biodistribution, and immune activation. The review addresses how…
Read the article →Biomaterials2009ResearchNon-viral Gene Delivery
Chen Guihua, Chen Wenjie, Wu Zhuang, Yuan Renxu, Li Hua, Gao Jinming, Shuai Xintao
Gene therapy could induce immunosuppression with greater durability and less toxicity than conventional agents like cyclosporine A, but T cells are notoriously refractory to non-viral gene delivery. An effective, T-cell-targeted, MRI-trackable non-viral vector is needed for immunosuppression in transplantation and…
Read the article →Advanced Materials2009ResearchNon-viral Gene Delivery
Joel Sunshine, Jordan J. Green, Kerry P. Mahon, Fan Yang, Ahmed A. Eltoukhy, David N. Nguyen, Robert Langer, Daniel G. Anderson
Viral vectors are efficient but face safety, manufacturing, and cargo-capacity limitations. Cationic polymers such as poly(β-amino ester)s (PBAEs) are promising non-viral alternatives, but their gene delivery efficacy varies across cell types. The study asked whether small-molecule end groups on a linear PBAE could…
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 →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 →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…
Read the article →Accounts of Chemical Research2008ReviewNon-viral Gene Delivery
Green, J. J.; Langer, R.; Anderson, D. G
Gene therapy has enormous therapeutic potential, but delivery remains the central bottleneck. Viral vectors are efficient but carry serious safety, immunogenicity, manufacturing, and cargo-capacity limitations. Nonviral vectors are safer and more scalable but typically orders of magnitude less effective. This Account…
Read the article →Bioorganic & Medicinal Chemistry (inferred from journal style; exact journal not stated in supplied excerpt)2007ResearchNon-viral Gene Delivery
Masato Yamagata, Takahito Kawano, Kouhei Shiba, Takeshi Mori, Yoshiki Katayama, Takuro Niidome
Gene carriers are often studied individually under different assay conditions, making direct structure–function comparisons difficult. The study compared dendritic poly(L-lysine) (KG6) and linear poly(L-lysine) (PLL) within the same experimental system to identify how carrier architecture affects DNA complex…
Read the article →Journal of Controlled Release2007ResearchNon-viral Gene Delivery
Xianfeng Zhou, Bin Liu, Xianghui Yu, Xiao Zha, Xizhen Zhang, Yu Chen, Xueyun Wang, Yinghua Jin, Yongge Wu, Yue Chen, Yaming Shan, Yan Chen, Junqiu Liu, Wei Kong, Jiacong Shen
DNA vaccines can induce antibody and CTL responses, but clinical translation is limited by weak potency and the need for high or repeated doses. The study addresses this by targeting DNA to antigen-presenting cells (APCs) and improving endosomal/lysosomal release, using mannose-bearing chitosan microspheres loaded…
Read the article →Bioconjugate Chemistry2006ResearchNon-viral Gene Delivery
Jordan J. Green, Julie Shi, Eugene Chiu, Elizaveta S. Leshchiner, Robert Langer, Daniel G. Anderson
Effective and safe gene delivery to primary endothelial cells in the presence of serum proteins is particularly challenging. Endothelial cells are important targets for cardiovascular disease and cancer, but existing nonviral vectors have low efficacy and/or cytotoxicity under serum-containing conditions. C32…
Read the article →Journal of Controlled Release2006ResearchNon-viral Gene Delivery
Katas H, Alpar Ho
siRNA has therapeutic potential but is limited by poor cellular uptake, rapid nuclease degradation, and poor blood stability. Chitosan was explored as a non-viral siRNA vector because of its low toxicity, biodegradability, biocompatibility, and cationic nature, but its use for siRNA delivery had not been…
Read the article →Expert Opinion on Therapeutic Patents2006ReviewNon-viral Gene Delivery
Mcneil Se, Perrie Y
Cationic liposomes have been developed for gene delivery for almost 20 years, but despite extensive effort, there has been limited progress toward an effective pharmaceutical product. Their transfection efficiency remains insufficient, and most clinical trials still rely on more potent viral vectors despite viral…
Read the article →Nature Materials2006ReviewNon-viral Gene Delivery
Putnam D
Synthetic polymer-based gene delivery vectors have been studied for two decades but remain far less efficient than viral vectors. The review addresses the need for improved design criteria and new synthetic strategies across nano-, micro-, and macroscale delivery systems to overcome formulation, organism-level, and…
Read the article →Journal of Controlled Release2006ReviewNon-viral Gene Delivery
Lv H, Zhang S, Wang B, Cui S, Yan J
Cationic lipids and polymers are promising non-viral gene delivery vectors because they are non-immunogenic, easy to produce, and not oncogenic, but toxicity remains a major obstacle to their clinical application. The review evaluates structural features of cationic compounds and summarises toxicity–structure…
Read the article →Gene Therapy2005ReviewNon-viral Gene Delivery
Dean Da, Strong Dd, Zimmer We.
Nonviral gene delivery is limited by multiple extracellular and intracellular barriers, but the nuclear envelope remains a major unresolved barrier, especially in nondividing cells. Plasmids must enter the nucleus to be transcribed, yet the mechanisms of plasmid nuclear import are much less understood than protein…
Read the article →Expert Opinion on Drug Delivery2005ReviewNon-viral Gene Delivery
Sérgio Simões, Ana Da Silva Filipe, Henrique Faneca, Miguel Mano, Nuno Penacho, Nejat Düzgüneş, Maria C. Pedroso De Lima
Cationic liposome–DNA complexes (lipoplexes) are a potentially viable non-viral alternative to viral vectors for therapeutic gene delivery, but they suffer from limited delivery/gene expression efficiency, toxicity at higher concentrations, adverse interactions with serum and cell surfaces, and poor tissue access…
Read the article →Nature Reviews Drug Discovery2005ReviewNon-viral Gene Delivery
Pack, D. W.; Hoffman, A. S.; Pun, S.; Stayton, P. S
The lack of safe and efficient gene-delivery methods remains a limiting obstacle to human gene therapy. Synthetic vectors are safer than recombinant viruses but generally lack sufficient efficacy, so polymers must be rationally designed to overcome extracellular and intracellular delivery barriers. PEI: Only 15–20%…
Read the article →Synthesis of Poly(β-amino esters) Optimized for Highly Effective Gene Delivery.2003ResearchNon-viral Gene Delivery
Akinc, A., Anderson, D. G., Lynn, D. M., & Langer, R. (2003).
Nonviral polymeric gene delivery vectors need systematic optimisation of nonstructural factors—polymer molecular weight, chain end-group, and polymer/DNA ratio—that strongly influence transfection, cytotoxicity, and DNA complexation. These factors had not been comprehensively studied together for poly(β-amino…
Read the article →Molecular Therapy2001ResearchNon-viral Gene Delivery
Adi Mesika, Irina Grigoreva, Muriel Zohar, Ziv Reich
Transfection efficiency of nonviral gene delivery systems remains unacceptably low, largely due to the inability of plasmid DNA to effectively translocate through the nuclear pore complexes (NPCs). While substantial progress has been made in transcriptionally regulated vectors, control over nuclear targeting is…
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