Nucleic Acid Therapeutics Using Polyplexes: A Journey of 50 Years (and Beyond)

Breathing Life into Polycations: Functionalization with pH-Responsive Endosomolytic Peptides and Polyethylene Glycol Enables siRNA Delivery

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A polymer library approach to suicide gene therapy for cancer

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Single-Stranded siRNAs Activate RNAi in Animals

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PEGylation of Poly(ethylene imine) Affects Stability of Complexes with Plasmid DNA under in Vivo Conditions in a Dose-Dependent Manner after Intravenous Injection into Mice

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Putative Role of Chloroquine in Gene Transfer into a Human Hepatoma Cell Line by DNA/Lactosylated Polylysine Complexes

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A stress-responsive RNA switch regulates VEGFA expression

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Mannose Polyethylenimine Conjugates for Targeted DNA Delivery into Dendritic Cells

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Different Strategies for Formation of PEGylated EGF-Conjugated PEI/DNA Complexes for Targeted Gene Delivery

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Overcoming the Nuclear Barrier: Cell Cycle Independent Nonviral Gene Transfer with Linear Polyethylenimine or Electroporation

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A novel magnetic crystal–lipid nanostructure for magnetically guided in vivo gene delivery

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Novel vectors for gene delivery formed by self-assembly of DNA with poly(l-lysine) grafted with hydrophilic polymers

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Gene gun-mediated skin transfection with interleukin 12 gene results in regression of established primary and metastatic murine tumors.

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Strategies to Improve DNA Polyplexes for in Vivo Gene Transfer: Will “Artificial Viruses” Be the Answer?

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Gene delivery using chitosan, trimethyl chitosan or polyethylenglycol-graft-trimethyl chitosan block copolymers: Establishment of structure–activity relationships in vitro

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PepFect 14, a novel cell-penetrating peptide for oligonucleotide delivery in solution and as solid formulation

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High-Efficiency Gene Transfer Mediated by Adenovirus Coupled to DNA–Polylysine Complexes

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Bioinspired pH-Responsive Polymers for the Intracellular Delivery of Biomolecular Drugs

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Regulation of endocytic pH by the Na+,K+-ATPase in living cells.

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The compaction of DNA helices into either continuous supercoils or folded-fiber rods and toroids

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A Potent New Class of Reductively Activated Peptide Gene Delivery Agents

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Branched Cationic Peptides for Gene Delivery: Role of Type and Number of Cationic Residues in Formation and in Vitro Activity of DNA Polyplexes

Plank, C., Tang, M. X., Wolfe, A. R., & Szoka, F. C. (1999) · Human Gene Therapy · doi:10.1089/10430349950019101 · Cited by 230

The use of lactoferrin as a ligand for targeting the polyamidoamine-based gene delivery system to the brain

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Condensation of DNA by trivalent cations. 1. Effects of DNA length and topology on the size and shape of condensed particles

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Reducible Poly(amido ethylenimine)s Designed for Triggered Intracellular Gene Delivery

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Development of a Nonviral Gene Delivery Vehicle for Systemic Application

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Improved packing of poly(ethylenimine)/DNA complexes increases transfection efficiency

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Enhancement of Gene Expression by Polyamidoamine Dendrimer Conjugates with α-, β-, and γ-Cyclodextrins

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Extracellular Barriers to in Vivo PEI and PEGylated PEI Polyplex-Mediated Gene Delivery to the Liver

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Design and synthesis of pH-responsive polymeric carriers that target uptake and enhance the intracellular delivery of oligonucleotides

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Disulfide-Linked Antibody−Maytansinoid Conjugates: Optimization of In Vivo Activity by Varying the Steric Hindrance at Carbon Atoms Adjacent to the Disulfide Linkage

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A Novel Mechanism Is Involved in Cationic Lipid-Mediated Functional siRNA Delivery

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Development of a non-viral multifunctional envelope-type nano device by a novel lipid film hydration method

Kogure, K., Moriguchi, R., Sasaki, K., Ueno, M., Futaki, S., & Harashima, H. (2004) · Journal of Controlled Release · doi:10.1016/j.jconrel.2004.04.024 · Cited by 218

Effects of Structure of β-Cyclodextrin-Containing Polymers on Gene Delivery

Hwang, S. J., Bellocq, N. C., & Davis, M. E. (2001) · Bioconjugate Chemistry · doi:10.1021/bc0001084 · Cited by 217

Current issues of RNAi therapeutics delivery and development

Haussecker, D. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.07.056 · Cited by 217

Actin Cytoskeleton as the Principal Determinant of Size-dependent DNA Mobility in Cytoplasm

Dauty, E., & Verkman, A. S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m412374200 · Cited by 215

Cholera Toxin: An Intracellular Journey into the Cytosol by Way of the Endoplasmic Reticulum

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Enzyme-free translation of DNA into sequence-defined synthetic polymers structurally unrelated to nucleic acids

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RAFT polymerization: an avenue to functional polymeric micelles for drug delivery

Stenzel, M. H. (2008) · Chemical Communications · doi:10.1039/b805464a · Cited by 212

Odd–Even Effect of Repeating Aminoethylene Units in the Side Chain of N-Substituted Polyaspartamides on Gene Transfection Profiles

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Exploring Chemical Modifications for siRNA Therapeutics: A Structural and Functional Outlook

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Polymer-Based Gene Delivery: A Current Review on the Uptake and Intracellular Trafficking of Polyplexes

Midoux, P., Breuzard, G., Gomez, J., & Pichon, C. (2008) · Current Gene Therapy · doi:10.2174/156652308786071014 · Cited by 209

Antigen-Specific Immune Responses and Clinical Outcome After Vaccination With Glioma-Associated Antigen Peptides and Polyinosinic-Polycytidylic Acid Stabilized by Lysine and Carboxymethylcellulose in Children With Newly Diagnosed Malignant Brainstem and Nonbrainstem Gliomas

Pollack, I. F., Jakacki, R. I., Butterfield, L. H., Hamilton, R. L., Panigrahy, A., Potter, D. M., Connelly, A. K., Dibridge, S. A., Whiteside, T. L., & Okada, H. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2013.54.0526 · Cited by 208

In Vivo Delivery to Tumors of DNA Complexed with Linear Polyethylenimine

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New coupling agents for the synthesis of immunotoxins containing a hindered disulfide bond with improved stability in vivo.

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Monomolecular collapse of plasmid DNA into stable virus-like particles

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Delivery of chemo-sensitizing siRNAs to HER2+-breast cancer cells using RNA aptamers

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Octaarginine-modified multifunctional envelope-type nano device for siRNA

Nakamura, Y., Kogure, K., Futaki, S., & Harashima, H. (2007) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.03.010 · Cited by 201

In situ single cell observation by fluorescence resonance energy transfer reveals fast intra‐cytoplasmic delivery and easy release of plasmid DNA complexed with linear polyethylenimine

Itaka, K., Harada, A., Yamasaki, Y., Nakamura, K., Kawaguchi, H., & Kataoka, K. (2004) · The Journal of Gene Medicine · doi:10.1002/jgm.470 · Cited by 201

Galactosylated chitosan-graft-poly(ethylene glycol) as hepatocyte-targeting DNA carrier

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Solid‐Phase Synthesis of Sequence‐Defined T‐, i‐, and U‐Shape Polymers for pDNA and siRNA Delivery

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Three-layered polyplex micelle as a multifunctional nanocarrier platform for light-induced systemic gene transfer

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Biodegradable, Endosome Disruptive, and Cationic Network-type Polymer as a Highly Efficient and Nontoxic Gene Delivery Carrier

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The cytosolic entry of diphtheria toxin catalytic domain requires a host cell cytosolic translocation factor complex

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Lessons learned from the clinical development and market authorization of Glybera

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Biodegradable Polyester, Poly[α-(4-Aminobutyl)-l-Glycolic Acid], as a Non-Toxic Gene Carrier

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An RGD–Oligolysine Peptide: A Prototype Construct for Integrin-Mediated Gene Delivery

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Magnetofection—A highly efficient tool for antisense oligonucleotide delivery in vitro and in vivo

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Systemic Delivery of Modified mRNA Encoding Herpes Simplex Virus 1 Thymidine Kinase for Targeted Cancer Gene Therapy

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Stability of siRNA polyplexes from poly(ethylenimine) and poly(ethylenimine)-g-poly(ethylene glycol) under in vivo conditions: Effects on pharmacokinetics and biodistribution measured by Fluorescence Fluctuation Spectroscopy and Single Photon Emission Computed Tomography (SPECT) imaging

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Chemical vectors for gene delivery: uptake and intracellular trafficking

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Carbon nanotubes as vectors for gene therapy: Past achievements, present challenges and future goals

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Application of membrane-active peptides for drug and gene delivery across cellular membranes

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Synthesis and Biological Evaluation of a Bioresponsive and Endosomolytic siRNA−Polymer Conjugate

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Thiolated Chitosan/DNA Nanocomplexes Exhibit Enhanced and Sustained Gene Delivery

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Reducible poly(amido ethylenimine) directed to enhance RNA interference

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Characters of dendritic poly(l-lysine) analogues with the terminal lysines replaced with arginines and histidines as gene carriers in vitro

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A leptin derived 30-amino-acid peptide modified pegylated poly-l-lysine dendrigraft for brain targeted gene delivery

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Proton Sponge Trick for pH-Sensitive Disassembly of Polyethylenimine-Based siRNA Delivery Systems

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Cellular Dynamics of EGF Receptor–Targeted Synthetic Viruses

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First "Antisense" Drug Will Treat CMV Retinitis

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Precision Polymers: Monodisperse, Monomer‐Sequence‐Defined Segments to Target Future Demands of Polymers in Medicine

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Bioreducible poly(amido amine)s with oligoamine side chains: Synthesis, characterization, and structural effects on gene delivery

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Breaking the Bonds: Non-viral Vectors Become Chemically Dynamic

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Efficient Gene Transfection by Histidine-Modified Chitosan through Enhancement of Endosomal Escape

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Endosomolysis by Masking of a Membrane-Active Agent (EMMA) for Cytoplasmic Release of Macromolecules

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In Vitro and In Vivo Gene Transfer by an Optimized α-Cyclodextrin Conjugate with Polyamidoamine Dendrimer

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Gene Transfer into Mammalian Cells Using Histone-Condensed Plasmid DNA

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Lactose-Poly(ethylene Glycol)-Grafted Poly-l-Lysine as Hepatoma Cell-Targeted Gene Carrier

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The Structure of PEG-Modified Poly(Ethylene Imines) Influences Biodistribution and Pharmacokinetics of Their Complexes with NF-κB Decoy in Mice

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Phase I/II Marker Lesion Study of Intravesical BC-819 DNA Plasmid in H19 Over Expressing Superficial Bladder Cancer Refractory to Bacillus Calmette-Guerin

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FGFR-targeted gene delivery mediated by supramolecular assembly between β-cyclodextrin-crosslinked PEI and redox-sensitive PEG

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Quantitative Comparison of Intracellular Unpacking Kinetics of Polyplexes by a Model Constructed From Quantum Dot-FRET

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Super‐resolved Fluorescence Microscopy: Nobel Prize in Chemistry 2014 for Eric Betzig, Stefan Hell, and William E. Moerner

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Size Reduction of Galactosylated PEI/DNA Complexes Improves Lectin-Mediated Gene Transfer into Hepatocytes

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Development of aptamer therapeutics

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snRNAs as the catalysts of pre-mRNA splicing

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Steric stabilization of poly(2‐(dimethylamino)ethyl methacrylate)‐based polyplexes mediates prolonged circulation and tumor targeting in mice

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T7 peptide-functionalized nanoparticles utilizing RNA interference for glioma dual targeting

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Modulated Protonation of Side Chain Aminoethylene Repeats in N-Substituted Polyaspartamides Promotes mRNA Transfection

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Protective copolymers for nonviral gene vectors: synthesis, vector characterization and application in gene delivery

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Tumor-targeted gene delivery via anti-HER2 antibody (trastuzumab, Herceptin®) conjugated polyethylenimine

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Small interfering RNA targeting Raf-1 inhibits tumor growth in vitro and in vivo

Leng, Q., & Mixson, A. J. (2005) · Cancer Gene Therapy · doi:10.1038/sj.cgt.7700831 · Cited by 85

Anti-JL1 antibody-conjugated poly (l-lysine) for targeted gene delivery to leukemia T cells

Suh, W., Chung, J.-K., Park, S.-H., & Kim, S. W. (2001) · Journal of Controlled Release · doi:10.1016/s0168-3659(01)00273-5 · Cited by 84

Gene Carriers Based on Hexanediol Diacrylate Linked Oligoethylenimine: Effect of Chemical Structure of Polymer on Biological Properties

Kloeckner, J., Bruzzano, S., Ogris, M., & Wagner, E. (2006) · Bioconjugate Chemistry · doi:10.1021/bc060133v · Cited by 83

Gene Transfer with Poly-Melittin Peptides

Chen, C.-P., Kim, J., Steenblock, E. R., Liu, D., & Rice, K. G. (2006) · Bioconjugate Chemistry · doi:10.1021/bc060028l · Cited by 82

Transfection study using multicellular tumor spheroids for screening non-viral polymeric gene vectors with low cytotoxicity and high transfection efficiencies

Han, M., Bae, Y., Nishiyama, N., Miyata, K., Oba, M., & Kataoka, K. (2007) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.05.012 · Cited by 82

Modified branched peptides with a histidine-rich tail enhance in vitro gene transfection

Leng, Q. (2005) · Nucleic Acids Research · doi:10.1093/nar/gni040 · Cited by 82

DNA interpolyelectrolyte complexes as a tool for efficient cell transformation

Kabanov, A. V., Astaf'eva, I. V., Chikindas, M. L., Rosenblat, G. F., Kiselev, V. I., Severin, E. S., & Kabanov, V. A. (1991) · Biopolymers · doi:10.1002/bip.360311210 · Cited by 81

Introducing PeptoPlexes: Polylysine‐block‐Polysarcosine Based Polyplexes for Transfection of HEK 293T Cells

Heller, P., Birke, A., Huesmann, D., Weber, B., Fischer, K., Reske‐Kunz, A. B., Bros, M., & Barz, M. (2014) · Macromolecular Bioscience · doi:10.1002/mabi.201400167 · Cited by 80

Optimized rod length of polyplex micelles for maximizing transfection efficiency and their performance in systemic gene therapy against stroma-rich pancreatic tumors

Dirisala, A., Osada, K., Chen, Q., Tockary, T. A., Takeda, K. M., Osawa, S., Liu, X., Ishii, T., Miyata, K., Oba, M., et al. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.03.037 · Cited by 80

Design of “Smart” polymers that can direct intracellular drug delivery

Hoffman, A. S., Stayton, P. S., Press, O. W., Murthy, N., Lackey, C. A., Cheung, C., Black, F. E., Campbell, J. S., Fausto, N., Kyriakides, T. R., et al. (2002) · Polymers for Advanced Technologies · doi:10.1002/pat.232 · Cited by 80

HPMA-oligolysine copolymers for gene delivery: Optimization of peptide length and polymer molecular weight

Johnson, R. N., Chu, D. S. H., Shi, J., Schellinger, J. G., Carlson, P. M., & Pun, S. H. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2011.07.009 · Cited by 79

A North American brain tumor consortium phase II study of poly-ICLC for adult patients with recurrent anaplastic gliomas

Butowski, N. A., Lamborn, K. R., Lee, B. L., Prados, M. D., Cloughesy, T. F., DeAngelis, L. M., Abrey, L. E., Fink, K., Lieberman, F. S., Mehta, M. P., et al. (2008) · Journal of Neuro-Oncology · doi:10.1007/s11060-008-9705-3 · Cited by 79

Delivery of siRNA mediated by histidine-containing reducible polycations

Stevenson, M., Ramos-Perez, V., Singh, S., Soliman, M., Preece, J. A., Briggs, S. S., Read, M. L., & Seymour, L. W. (2008) · Journal of Controlled Release · doi:10.1016/j.jconrel.2008.05.014 · Cited by 78

Low molecular weight hyaluronan shielding of DNA/PEI polyplexes facilitates CD44 receptor mediated uptake in human corneal epithelial cells

Hornof, M., de la Fuente, M., Hallikainen, M., Tammi, R., & Urtti, A. O. (2007) · The Journal of Gene Medicine · doi:10.1002/jgm.1125 · Cited by 78

High resolution respirometry analysis of polyethylenimine-mediated mitochondrial energy crisis and cellular stress: Mitochondrial proton leak and inhibition of the electron transport system

Hall, A., Larsen, A. K., Parhamifar, L., Meyle, K. D., Wu, L., & Moghimi, S. M. (2013) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2013.07.001 · Cited by 77

A Phase I Study of Immunization Using Particle-Mediated Epidermal Delivery of Genes for gp100 and GM-CSF into Uninvolved Skin of Melanoma Patients

Cassaday, R. D., Sondel, P. M., King, D. M., Macklin, M. D., Gan, J., Warner, T. F., Zuleger, C., Bridges, A. J., Schalch, H., Kim, K. M., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-2039 · Cited by 77

Translating Genomics for Precision Cancer Medicine

Roychowdhury, S., & Chinnaiyan, A. M. (2014) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-090413-025552 · Cited by 76

Block copolymer micelles in nanomedicine applications

Cabral, H., Miyata, K., Osada, K., & Kataoka, K. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00199 · Cited by 1,309

Gene therapy clinical trials worldwide to 2012 – an update

Ginn, S. L., Alexander, I. E., Edelstein, M. L., Abedi, M. R., & Wixon, J. (2013) · The Journal of Gene Medicine · doi:10.1002/jgm.2698 · Cited by 1,159

Gene therapy clinical trials worldwide to 2017: An update

Ginn, S. L., Amaya, A. K., Alexander, I. E., Edelstein, M., & Abedi, M. R. (2018) · The Journal of Gene Medicine · doi:10.1002/jgm.3015 · Cited by 903

Intracellular Delivery by Membrane Disruption: Mechanisms, Strategies, and Concepts

Stewart, M. P., Langer, R., & Jensen, K. F. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00678 · Cited by 747

Nanodelivery of nucleic acids

Mendes, B. B., Conniot, J., Avital, A., Yao, D., Jiang, X., Zhou, X., Sharf-Pauker, N., Xiao, Y., Adir, O., Liang, H., et al. (2022) · Nature Reviews Methods Primers · doi:10.1038/s43586-022-00104-y · Cited by 719