Abstract
The success of gene therapy is largely dependent on the development of the gene delivery vector. Recently, gene transfection into target cells using naked DNA, which is a simple and safe approach, has been improved by combining several physical techniques, for example, electroporation, gene gun, ultrasound and hydrodynamic pressure. Chemical approaches have been utilized to improve the efficiency and cell specificity of gene transfer. Novel gene carrier molecules, which facilitate DNA escape from the endosome into the cytosol, have been developed. Several functional polymers, which enable controlled release of DNA in response to an environmental change, have also been reported. Plasmids with reduced number of CpG motifs, the use of PCR fragments and the sequential injection method have been established for the reduction of immune response triggered by plasmid DNA. Construction of a long-lasting gene expression system is also an important theme for nonviral gene therapy. To date, tissue-specific expression, self-replicating and integrating plasmid systems have been reported. Improvement of delivery methods together with intelligent design of the DNA itself has brought about large degrees of enhancement in the efficiency, specificity and temporal control of nonviral vectors.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Nishikawa M, Huang L . Nonviral vectors in the new millennium: delivery barriers in gene transfer Hum Gene Ther 2001 12: 861–870
Li S, Ma Z . Nonviral gene therapy Curr Gene Ther 2001 1: 201–226
Somiari S et al. Theory and in vivo application of electroporative gene delivery Mol Ther 2000 2: 178–187
Drabick JJ et al. Cutaneous transfection and immune responses to intradermal nucleic acid vaccination are significantly enhanced by in vivo electropermeabilization Mol Ther 2001 3: 249–255
Maruyama H et al. Skin-targeted gene transfer using in vivo electroporation Gene Ther 2001 8: 1808–1812
Dujardin N, Van Der Smissen P, Preat V . Topical gene transfer into rat skin using electroporation Pharm Res 2001 18: 61–66
Chesnoy S, Huang L . Enhanced cutaneous gene delivery following intradermal injection of naked DNA in a high ionic strength solution Mol Ther 2002 5: 57–62
Widera G et al. DNA vaccine delivery and immunogenicity by electroporation in vivo J Immunol 2000 164: 4635–4640
Hanna E et al. Intramuscular electroporation delivery of IL-12 gene for treatment of squamous cell carcinoma located at distant site Cancer Gene Ther 2001 8: 151–157
Li S et al. Intramuscular electroporation delivery of IFN-α gene therapy for inhibition of tumor growth located at a distant site Gene Ther 2001 8: 400–407
Tamura T et al. Intratumoral delivery of interleukin 12 expression plasmids with in vivo electroporation is effective for colon and renal cancer Hum Gene Ther 2001 12: 1265–1276
Liu F, Huang L . A syringe electrode device for simultaneous injection of DNA and electrotransfer Mol Ther 2002 5: 323–328
Heller L et al. Electrically mediated plasmid DNA delivery to hepatocellular carcinomas in vivo Gene Ther 2000 7: 826–829
Liu F, Hunag L . Electric gene transfer to the liver following systemic administration of plasmid DNA Gene Ther 1998 8: 1531–1537
Lin MT, Pulkkinen L, Uitto J, Yoon K . The gene gun: current application in cutaneous gene therapy Int J Dermatol 2000 39: 161–170
Davidson JM, Krieg T, Eming SA . Particle-mediated gene therapy of wounds Wound Repair Regen 2000 8: 452–459
Muangmoonchai R et al. Transfection of liver in vivo by biolistic particle delivery: its use in the investigation of cytochrome P450 gene regulation Mol Biotechnol 2002 20: 145–151
Kuriyama S et al. Particle-mediated gene transfer into murine livers using a newly developed gene gun Gene Ther 2000 7: 1132–1136
Yoshida S et al. Direct immunization of malaria DNA vaccine into the liver by gene gun protects against lethal challenge of Plasmodium berghei sporozoite Biochem Biophys Res Commun 2000 271: 107–115
Newman CM, Lawrie A, Brisken AF, Cumberland DC . Ultrasound gene therapy: on the road from concept to reality Echocardiography 2001 18: 339–347
Amabile PG et al. High-efficiency endovascular gene delivery via therapeutic ultrasound J Am Coll Cardiol 2001 37: 1975–1980
Taniyama Y et al. Local delivery of plasmid DNA into rat carotid artery using ultrasound Circulation 2002 105: 1233–1239
Teupe C et al. Vascular gene transfer of phosphomimetic endothelial nitric oxide synthase (S1177D) using ultrasound-enhanced destruction of plasmid-loaded microbubbles improves vasoreactivity Circulation 2002 105: 1104–1109
Unger EC, Hersh E, Vannan M, McCreery T . Gene delivery using ultrasound contrast agents Echocardiography 2001 18: 355–361
Lawrie A et al. Microbubble-enhanced ultrasound for vascular gene delivery Gene Ther 2000 7: 2023–2027
Song J et al. Influence of injection site, microvascular pressure and ultrasound variables on microbubble-mediated delivery of microspheres to muscle J Am Coll Cardiol 2002 39: 726–731
Shohet RV et al. Echocardiographic destruction of albumin microbubbles directs gene delivery to the myocardium Circulation 2000 101: 2554–2556
Endoh M et al. Fetal gene transfer by intrauterine injection with microbubble-enhanced ultrasound Mol Ther 2002 5; 501–508
Budker V et al. Hypothesis: naked plasmid DNA is taken up by cells in vivo by a receptor-mediated process J Gene Med 2000 2: 76–88
Siess DC et al. A human gene coding for a membrane-associ-ated nucleic acid-binding protein J Biol Chem 2000 275: 33655–33662
Liu F, Huang L . Noninvasive gene delivery to the liver by mechanical massage Hepatology 2002 35: 1314–1319
Zhang G et al. Efficient expression of naked DNA delivered intraarterially to limb muscles of nonhuman primates Hum Gene Ther 2001 12: 427–438
Liu F, Huang L . Improving plasmid DNA-mediated liver gene transfer by prolonging its retention in the hepatic vasculature J Gene Med 2001 3: 569–576
Liu F, Nishikawa M, Clemens PR, Huang L . Transfer of full-length Dmd to the diaphragm muscle of Dmd(mdx/mdx) mice through systemic administration of plasmid DNA Mol Ther 2001 4: 45–51
Dauty E, Remy JS, Blessing T, Behr JP . Dimerizable cationic detergents with a low cmc condense plasmid DNA into nanometric particles and transfect cells in culture J Am Chem Soc 2001 123: 9227–9234
McKenzie DL, Kwok KY, Rice KG . A potent new class of reductively activated peptide gene delivery agents J Biol Chem 2000 275: 9970–9977
Park Y, Kwok KY, Boukarim C, Rice KG . Synthesis of sulfhydryl cross-linking poly(ethylene glycol)-peptides and glyco-peptides as carriers for gene delivery Bioconjug Chem 2002 13: 232–239
Wightman L et al. Different behavior of branched and linear polyethylenimine for gene delivery in vitro and in vivo J Gene Med 2001 3: 362–372
Lim YB et al. Biodegradable polyester, poly[α-(4-aminobutyl)-L-glycolic acid], as a non-toxic gene carrier Pharm Res 2000 17: 811–816
Koh JJ et al. Degradable polymeric carrier for the delivery of IL-10 plasmid DNA to prevent autoimmune insulitis of NOD mice Gene Ther 2000 7: 2099–2104
Maheshwari A et al. Soluble biodegradable polymer-based cytokine gene delivery for cancer treatment Mol Ther 2000 2: 121–130
Ahn CH, Chae SY, Bae YH, Kim SW . Biodegradable poly(ethylenimine) for plasmid DNA delivery J Control Release 2002 80: 273–282
Wang J, Mao HQ, Leong KW . A novel biodegradable gene carrier based on polyphosphoester J Am Chem Soc 2001 123: 9480–9581
Kurisawa M, Yokoyama M, Okano T . Gene expression control by temperature with thermo-responsive polymeric gene carriers J Control Release 2000 69: 127–137
Jeong B, Kim SW, Bae YH . Thermosensitive sol-gel reversible hydrogels Adv Drug Deliv Rev 2002 54: 37–51
Jeong B, Bae YH, Kim SW . Drug release from biodegradable injectable thermosensitive hydrogel of PEG–PLGA–PEG triblock copolymers J Control Release 2000 63: 155–163
Harada-Shiba M et al. Polyion complex micelles as vectors in gene therapy – pharmacokinetics and in vivo gene transfer Gene Ther 2002 9: 407–414
Turk MJ, Reddy JA, Chmielewski JA, Low PS . Characterization of a novel pH-sensitive peptide that enhances drug release from folate-targeted liposomes at endosomal pHs Biochim Biophys Acta 2002 1559: 56–68
Lee H, Jeong JH, Park TG . A new gene delivery formulation of polyethylenimine/DNA complexes coated with PEG conjugated fusogenic peptide J Control Release 2001 76: 183–192
Rittner K et al. New basic membrane-destabilizing peptides for plasmid-based gene delivery in vitro and in vivo Mol Ther 2002 5: 104–114
Bremner KH, Seymour LW, Pouton CW . Harnessing nuclear localization pathways for transgene delivery Curr Opin Mol Ther 2001 3: 170–177
Tachibana R, Harashima H, Shinohara Y, Kiwada H . Quantitative studies on the nuclear transport of plasmid DNA and gene expression employing nonviral vectors Adv Drug Deliv Rev 2001 52: 219–226
Cartier R, Reszka R . Utilization of synthetic peptides containing nuclear localization signals for nonviral gene transfer systems Gene Ther 2002 9: 157–167
Tousignant JD et al. Comprehensive analysis of the acute toxicities induced by systemic administration of cationic lipid:plasmid DNA complexes in mice Hum Gene Ther 2000 11: 2493–2513
Yew NS et al. Reduced inflammatory response to plasmid DNA vectors by elimination and inhibition of immunostimulatory CpG motifs Mol Ther 2000 1: 255–262
Hofman CR et al. Efficient in vivo gene transfer by PCR amplified fragment with reduced inflammatory activity Gene Ther 2001 8: 71–74
Li S et al. Targeted gene delivery to pulmonary endothelium by anti-PECAM antibody Am J Physiol Lung Cell Mol Physiol 2000 278L: 504–511
Tan Y et al. Sequential injection of cationic liposome and plasmid DNA effectively transfects the lung with minimal inflammatory toxicity Mol Ther 2001 3: 673–682
Miao CH et al. Inclusion of the hepatic locus control region, an intron, and untranslated region increases and stabilizes hepatic factor IX gene expression in vivo but not in vitro Mol Ther 2000 1: 522–532
Chen ZY et al. Linear DNAs concatemerize in vivo and result in sustained transgene expression in mouse liver Mol Ther 2001 3: 403–410
Maruyama-Tabata H et al. Effective suicide gene therapy in vivo by EBV-based plasmid vector coupled with polyamidoamine dendrimer Gene Ther 2000 7: 53–60
Tomiyasu K et al. Direct intra-cardiomuscular transfer of beta2-adrenergic receptor gene augments cardiac output in cardiomyopathic hamsters Gene Ther 2000 7: 2087–2093
Cui FD et al. Highly efficient gene transfer into murine liver achieved by intravenous administration of naked Epstein–Barr virus (EBV)-based plasmid vectors Gene Ther 2001 8: 1508–1513
Stoll SM et al. Epstein–Barr virus/human vector provides high-level, long-term expression of α1-antitrypsin in mice Mol Ther 2001 4: 122–129
Ivics Z, Hackett PB, Plasterk RH, Izsvak Z . Molecular reconstruction of Sleeping Beauty, a Tc1-like transposon from fish, and its transposition in human cells Cell 1997 91: 501–510
Yant SR et al. Somatic integration and long-term transgene expression in normal and haemophilic mice using a DNA transposon system Nat Genet 2000 25: 35–41
Thyagarajan B et al. Site-specific genomic integration in mammalian cells mediated by phage phiC31 integrase Mol Cell Biol 2001 21: 3926–3934
Olivares EC, Hollis RP, Calos MP . Phage R4 integrase mediates site-specific integration in human cells Gene 2001 278: 167–176
Sclimenti CR, Thyagarajan B, Calos MP . Directed evolution of a recombinase for improved genomic integration at a native human sequence Nucleic Acids Res 2001 29: 5044–5051
Stoll SM, Ginsburg DS, Calos MP . Phage TP901-1 site-specific integrase functions in human cells J Bacteriol 2002 184: 3657–3663
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Niidome, T., Huang, L. Gene Therapy Progress and Prospects: Nonviral vectors. Gene Ther 9, 1647–1652 (2002). https://doi.org/10.1038/sj.gt.3301923
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.gt.3301923
Keywords
This article is cited by
-
Gene therapy and gene correction: targets, progress, and challenges for treating human diseases
Gene Therapy (2022)
-
Graphene-based nanomaterials for breast cancer treatment: promising therapeutic strategies
Journal of Nanobiotechnology (2021)
-
Novel Self-assembly Coordination Lipid Polymers that Fold into Toroids with DNA-Delivery Potential
Journal of Inorganic and Organometallic Polymers and Materials (2021)
-
Nanotechnology based CRISPR/Cas9 system delivery for genome editing: Progress and prospect
Nano Research (2019)
-
Controlled release of DNA from zinc and magnesium ion-doped hydroxyapatites
Research on Chemical Intermediates (2019)