Enhanced gene delivery by avidin-displaying baculovirus.

Flexible alteration of virus surface properties would be beneficial for enhanced and targeted gene delivery. A useful approach could be based on a high-affinity receptor-ligand pair, such as avidin and biotin. In this study, we have constructed an avidin-displaying baculovirus, Baavi. Avidin display was expected to enhance cell transduction due to the high positive charge of avidin in physiological pH and to provide a binding site for covering the virus with desired biotinylated ligands. Successful incorporation of avidin on the virus envelope was detected by immunoblotting and electron microscopy. Multiple biotin-binding sites per virus were detected with fluorescence-correlation spectroscopy and tight biotin binding was observed using an optical biosensor, IAsys. Baavi showed a 5-fold increase in transduction efficiency in rat malignant glioma cells (BT4C) and a 26-fold increase in rabbit aortic smooth muscle (RAASMC) cells compared to wild-type baculovirus. Enhanced transduction was also observed with biotinylated target cells. Biotinylated epidermal growth factor (EGF) enabled specific targeting of the virus with high efficiency to EGF receptor-expressing (SKOV-3) cells. An additional advantage of the avidin display was demonstrated with biotinylated paramagnetic particles, which enabled magnetic targeting. Altogether, we show that avidin display is a rapid and versatile method to improve viral properties for gene delivery.

[1]  R. Samulski,et al.  Targeted adeno-associated virus vector transduction of nonpermissive cells mediated by a bispecific F(ab'γ)2 antibody , 1999, Nature Biotechnology.

[2]  K. Peng.  Strategies for targeting therapeutic gene delivery. , 1999, Molecular medicine today.

[3]  D. Danon,et al.  Redistribution of surface anionic sites on the luminal front of blood vessel endothelium after interaction with polycationic ligand , 1976, The Journal of cell biology.

[4]  Ian M. Jones,et al.  Eukaryotic Virus Display: Engineering the Major Surface Glycoprotein of the Autographa californica Nuclear Polyhedrosis Virus (AcNPV) for the Presentation of Foreign Proteins on the Virus Surface , 1995, Bio/Technology.

[5]  J. Cory,et al.  Use of baculoviruses as biological insecticides , 1997, Molecular biotechnology.

[6]  Stefan Kochanek,et al.  Antibody-Mediated Targeting of an Adenovirus Vector Modified To Contain a Synthetic Immunoglobulin G-Binding Domain in the Capsid , 2003, Journal of Virology.

[7]  Sun U. Song,et al.  Effective transduction of osteogenic sarcoma cells by a baculovirus vector. , 2003, The Journal of general virology.

[8]  F. Farzaneh,et al.  Streptavidin paramagnetic particles provide a choice of three affinity-based capture and magnetic concentration strategies for retroviral vectors. , 2001, Molecular therapy : the journal of the American Society of Gene Therapy.

[9]  J. Zimmerberg,et al.  Large-scale production of pseudotyped lentiviral vectors using baculovirus GP64. , 2003, Human gene therapy.

[10]  C. Dawson,et al.  Biotinylation of membrane proteins accessible via the pulmonary circulation in normal and hyperoxic rats. , 1997, The American journal of physiology.

[11]  R. Poston,et al.  Cell biotinylation provides a sensitive and effective detection technique for cellular adhesion assays: comparison with existing methods. , 2001, Journal of immunological methods.

[12]  D. Hammer,et al.  Binding and fusion of Autographa californica nucleopolyhedrovirus to cultured insect cells. , 1997, The Journal of general virology.

[13]  F. Szoka,et al.  Efficient adventitial gene delivery to rabbit carotid artery with cationic polymer–plasmid complexes , 1999, Gene Therapy.

[14]  W. Oyen,et al.  Pretargeted radioimmunotherapy of cancer: progress step by step. , 2003, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[15]  H. Ushijima,et al.  Characterization of cell-surface determinants important for baculovirus infection. , 2001, Virology.

[16]  U. Wojda,et al.  Surface membrane biotinylation efficiently mediates the endocytosis of avidin bioconjugates into nucleated cells. , 1999, Bioconjugate chemistry.

[17]  R. Bjerkvig,et al.  Herpes simplex virus thymidine kinase gene therapy in experimental rat BT4C glioma model: Effect of the percentage of thymidine kinase-positive glioma cells on treatment effect, survival time, and tissue reactions , 2000, Cancer Gene Therapy.

[18]  F. Grosveld,et al.  Baculovirus Infection of Nondividing Mammalian Cells: Mechanisms of Entry and Nuclear Transport of Capsids , 2001, Journal of Virology.

[19]  D. Brough,et al.  Increased in vitro and in vivo gene transfer by adenovirus vectors containing chimeric fiber proteins , 1997, Journal of virology.

[20]  L. Guterman,et al.  A Novel Intravascular Drug Delivery Method Using Endothelial Biotinylation and Avidin-Biotin Binding , 2001, Drug delivery.

[21]  R. R. Granados,et al.  The biology of baculoviruses , 1986 .

[22]  J. Barsoum,et al.  Baculovirus vector requires electrostatic interactions including heparan sulfate for efficient gene transfer in mammalian cells , 1999, The journal of gene medicine.

[23]  K. Airenne,et al.  Production of recombinant avidin in Escherichia coli. , 1994, Gene.

[24]  Thomas A Kost,et al.  Recombinant baculoviruses as mammalian cell gene-delivery vectors. , 2002, Trends in biotechnology.

[25]  O. Laitinen,et al.  Baculovirus-mediated periadventitial gene transfer to rabbit carotid artery , 2000, Gene Therapy.

[26]  L. Volkman,et al.  In Vitro Survey of Autographa californica Nuclear Polyhedrosis Virus Interaction with Nontarget Vertebrate Host Cells , 1983, Applied and environmental microbiology.

[27]  C Alexiou,et al.  Clinical applications of magnetic drug targeting. , 2001, The Journal of surgical research.

[28]  M. Wilchek,et al.  Sodium dodecyl sulfate‐polyacrylamide gel electrophoretic method for assessing the quaternary state and comparative thermostability of avidin and streptavidin , 1996, Electrophoresis.

[29]  M. Gill,et al.  The Structural Organization of Cationic Lipid-DNA Complexes* , 2002, The Journal of Biological Chemistry.

[30]  M. Vuento,et al.  Properties of Baculovirus Particles Displaying GFP Analyzed by Fluorescence Correlation Spectroscopy , 2002, Biological chemistry.

[31]  D. O'reilly,et al.  Baculovirus expression vectors: a laboratory manual. , 1992 .

[32]  Meir Wilchek,et al.  Recombinant NeutraLite Avidin: a non‐glycosylated, acidic mutant of chicken avidin that exhibits high affinity for biotin and low non‐specific binding properties , 2000, FEBS letters.

[33]  S. Spence,et al.  Redirected infection of directly biotinylated recombinant adenovirus vectors through cell surface receptors and antigens. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Varpu Marjomäki,et al.  Baculovirus capsid display: a novel tool for transduction imaging. , 2003, Molecular therapy : the journal of the American Society of Gene Therapy.

[35]  W. Pardridge,et al.  Enhanced cellular uptake of biotinylated antisense oligonucleotide or peptide mediated by avidin, a cationic protein , 1991, FEBS letters.

[36]  C Russell Middaugh,et al.  Barriers to nonviral gene delivery. , 2003, Journal of pharmaceutical sciences.

[37]  T. Nikkari,et al.  Transfer of 15-lipoxygenase gene into rabbit iliac arteries results in the appearance of oxidation-specific lipid-protein adducts characteristic of oxidized low density lipoprotein. , 1995, The Journal of clinical investigation.

[38]  J Henke,et al.  Magnetofection: enhancing and targeting gene delivery by magnetic force in vitro and in vivo , 2002, Gene Therapy.

[39]  M. Turunen,et al.  Peptide-retargeted adenovirus encoding a tissue inhibitor of metalloproteinase-1 decreases restenosis after intravascular gene transfer. , 2002, Molecular therapy : the journal of the American Society of Gene Therapy.

[40]  C. Oker-Blom,et al.  Developments in the use of baculoviruses for the surface display of complex eukaryotic proteins. , 2001, Trends in biotechnology.

[41]  Chicken avidin-related proteins show altered biotin-binding and physico-chemical properties as compared with avidin. , 2002 .

[42]  Sanjay Kumar,et al.  Conjugate-Based Targeting of Recombinant Adeno-Associated Virus Type 2 Vectors by Using Avidin-Linked Ligands , 2002, Journal of Virology.

[43]  G. Blissard,et al.  Baculovirus gp64 envelope glycoprotein is sufficient to mediate pH-dependent membrane fusion , 1992, Journal of virology.

[44]  C. Oker-Blom,et al.  Specific binding of baculoviruses displaying gp64 fusion proteins to mammalian cells. , 2001, Biochemical and biophysical research communications.

[45]  L. Seymour,et al.  Adenoviral vectors: Systemic delivery and tumor targeting , 2002, Cancer Gene Therapy.

[46]  W. Pardridge,et al.  Pharmacokinetics and delivery of tat and tat-protein conjugates to tissues in vivo. , 2001, Bioconjugate chemistry.

[47]  Xianglin Shi,et al.  New insights into the role of nuclear factor-kappaB, a ubiquitous transcription factor in the initiation of diseases. , 1999, Clinical chemistry.

[48]  J Barsoum,et al.  Efficient transduction of mammalian cells by a recombinant baculovirus having the vesicular stomatitis virus G glycoprotein. , 1997, Human gene therapy.

[49]  A. Plückthun,et al.  New protein engineering approaches to multivalent and bispecific antibody fragments. , 1997, Immunotechnology : an international journal of immunological engineering.