Molecular therapy. Oncology2026ReviewNon-viral Gene DeliveryDrug Delivery
Bedada At, Genet S
Cancer remains a formidable global health challenge, representing the second leading cause of mortality worldwide. In 2023, there were approximately 18.5 million new cancer cases and over 10 million deaths globally, with projections estimating 30.5 million new cases and 18.6 million deaths annually by 2050. In the…
Read the article →Viruses2026ReviewNon-viral Gene Delivery
Zhang M, Mohess J, Cheung J, Du Q, Qiu J, Wang J
Osteoarthritis (OA) is the most prevalent joint disease, which is pathologically characterized by articular cartilage degradation, chronic synovial inflammation, subchondral bone remodeling, and osteophyte formation. Patients with OA suffer from joint pain, deformity, and functional impairment. Current therapies…
Read the article →Signal Transduction and Targeted Therapy2021ReviewNon-viral Gene Delivery
Chen L, Hong W, Ren W, Xu T, Qian Z, He Z.
Synthetic nanoparticles face physiological barriers, RES clearance, and unintended biological interactions despite PEGylation and ligand grafting. Biological vectors—cell membranes, extracellular vesicles (EVs), and viruses—offer biocompatibility, biodegradability, immune evasion, and natural targeting. This review…
Read the article →Trends in Molecular Medicine2021ReviewNon-viral Gene Delivery
Likely Citation: Swingle Kl, Hamilton Ag, Mitchell Mj
mRNA is degraded by nucleases and cannot easily cross cell membranes because of its large size and negative charge. Delivery therefore requires encapsulation in vehicles such as lipid nanoparticles (LNPs) to enable protein replacement, vaccines, and gene-editing applications. Onpattro was the first FDA-approved…
Read the article →Nature Communications2020ReviewNon-viral Gene Delivery
Karen Bulaklak And Charles A. Gersbach
Gene therapy is at an inflection point: recent approvals and clinical successes have validated the field, but broader application is still limited by immune responses to vectors, inefficient delivery outside the retina and liver, and regulatory frameworks that are poorly suited to personalised, potentially curative…
Read the article →Pharmaceutics2020ReviewNon-viral Gene Delivery
Wahane A, Waghmode A, Kapphahn A, Dhur K, Gupta A, Bahal R
Nucleic acid analogs and genome-editing proteins have broad therapeutic potential, but clinical translation is limited by poor cell- and organ-specific delivery, endosomal entrapment, enzymatic degradation, and short bioavailability. The review examines lipid- and polymer-based non-viral vectors as strategies to…
Read the article →Nature Reviews Chemistry2018ReviewNon-viral Gene Delivery
Irene Lostalé-Seijo And Javier Montenegro
Gene therapy has enormous therapeutic potential, but clinical translation is limited by the delivery problem: nucleic acids are negatively charged, unstable, and must overcome multiple biological barriers to reach their intracellular site of action. Viral vectors are efficient but suffer from immunogenicity, limited…
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 →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 →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 →Journal of Drug Targeting (J Drug Target)2013ReviewNon-viral Gene Delivery
Jing Yao, Ying Fan, Yuanke Li, And Leaf Huang
Non-viral gene delivery systems are safer than viral vectors but are highly inefficient at nuclear delivery. Only ~10–20% of applied plasmid DNA enters targeted cells, and only ~1–5% of the applied dose reaches the nucleus. The nuclear envelope is a major barrier to transgene delivery, and there is a need for “smart”…
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 →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 →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 →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 →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 →1999ReviewNon-viral Gene Delivery
Godbey, W. T.; Wu, K. K.; Mikos, A. G
Gene therapy still lacks safe and efficient delivery vectors. PEI has emerged as a promising non-viral polycation because it condenses DNA and mediates endosomal escape, but its transfection mechanism, targeting potential, and toxicity require clearer understanding. This review summarises PEI chemistry, PEI/DNA…
Read the article →Molecular Membrane Biology1998ReviewNon-viral Gene Delivery
Hope Mj, Mui B, Ansell S, Ahkong Qf
Polymeric nucleic acid drugs—plasmid DNA, antisense oligonucleotides, and ribozymes—require protection from nucleases and efficient intracellular delivery to cytoplasm/nucleus. Viral vectors are efficient but immunogenic and safety-limited; non-viral cationic lipid systems are promising, but the mechanism of…
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…
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