E A Chiocca

Brigham and Women's Hospital , Boston, Massachusetts, United States

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Publications (101)533.51 Total impact

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    ABSTRACT: Despite advances in multimodal therapy, patients with malignant glioma have a dismal prognosis. Aberrant angiogenesis and diffuse glioma cell invasion are major obstacles for effective treatment. Therefore, investigation of angiogenesis and invasion is essential for the development of a curative therapy. We established animal models that histologically mimic two invasive and angiogenic phenotypes of glioma, ie, angiogenesis-dependent invasion (J3T-1) and angiogenesis-independent invasion (J3T-2). In our previous study, comparative proteomic analysis showed that annexin A2 was more highly expressed in J3T-1 than in J3T-2. In this study, the function of annexin A2 in malignant glioma in relation to angiogenesis and invasion was investigated using these animal models.
    Neuro-oncology. 07/2014; 16 Suppl 3:iii10.
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    ABSTRACT: Oncolytic viral (OV) therapy has been considered as a promising treatment modality for brain tumors. Vasculostatin, the fragment of brain-specific angiogenesis inhibitor-1, shows anti-angiogenic activity against malignant gliomas. Previously, a vasculostatin-expressing oncolytic herpes simplex virus-1, Rapid Antiangiogenesis Mediated By Oncolytic virus (RAMBO), was reported to have a potent antitumor effect. Here, we investigated the therapeutic efficacy of RAMBO and cilengitide, an integrin inhibitor, combination therapy for malignant glioma. In vitro, tube formation was significantly decreased in RAMBO and cilengitide combination treatment compared with RAMBO or cilengitide monotherapy. Moreover, combination treatment induced a synergistic suppressive effect on endothelial cell migration compared with the control virus. RAMBO, combined with cilengitide, induced synergistic cytotoxicity on glioma cells. In the caspase-8 and -9 assays, the relative absorption of U87ΔEGFR cell clusters treated with cilengitide and with RAMBO was significantly higher than that of those treated with control. In addition, the activity of caspase 3/7 was significantly increased with combination therapy. In vivo, there was a significant increase in the survival of mice treated with combination therapy compared with RAMBO or cilengitide monotherapy. These results indicate that cilengitide enhanced vasculostatin-expressing OV therapy for malignant glioma and provide a rationale for designing future clinical trials combining these two agents.Cancer Gene Therapy advance online publication, 5 July 2013; doi:10.1038/cgt.2013.38.
    Cancer gene therapy 07/2013; · 3.13 Impact Factor
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    ABSTRACT: Epstein-Barr virus (EBV)-associated B-cell lymphoproliferative disease (LPD) after hematopoietic stem cell or solid organ transplantation remains a life-threatening complication. Expression of the virus-encoded gene product, EBER, has been shown to prevent apoptosis via blockade of PKR activation. As PKR is a major cellular defense against Herpes simplex virus (HSV), and oncolytic HSV-1 (oHSV) mutants have shown promising antitumor efficacy in preclinical models, we sought to determine whether EBV-LPD cells are susceptible to infection by oHSVs. We tested three primary EBV-infected lymphocyte cell cultures from neuroblastoma (NB) patients as models of naturally acquired EBV-LPD. NB12 was the most susceptible, NB122R was intermediate and NB88R2 was essentially resistant. Despite EBER expression, PKR was activated by oHSV infection. Susceptibility to oHSV correlated with the expression of the HSV receptor, nectin-1. The resistance of NB88R2 was reversed by exogenous nectin-1 expression, whereas downregulation of nectin-1 on NB12 decreased viral entry. Xenografts derived from the EBV-LPDs exhibited only mild (NB12) or no (NB88R2) response to oHSV injection, compared with a NB cell line that showed a significant response. We conclude that EBV-LPDs are relatively resistant to oHSV virotherapy, in some cases, due to low virus receptor expression but also due to intact antiviral PKR signaling.Gene Therapy advance online publication, 20 December 2012; doi:10.1038/gt.2012.93.
    Gene therapy 12/2012; · 4.75 Impact Factor
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    ABSTRACT: Peripheral neuropathic pain is one of the most common and debilitating complications of diabetes. Several genes have been shown to be effective in reducing neuropathic pain in animal models of diabetes after transfer to the dorsal root ganglion using replication-defective herpes simplex virus (HSV)1-based vectors, yet there has never been a comparative analysis of their efficacy. We compared four different HSV1-based vectors engineered to produce one of two opioid receptor agonists (enkephalin or endomorphin), or one of two isoforms of glutamic acid decarboxylase (GAD65 or GAD67), alone and in combination, in the streptozotocin-induced diabetic rat and mouse models. Our results indicate that a single subcutaneous hindpaw inoculation of vectors expressing GAD65 or GAD67 reduced diabetes-induced mechanical allodynia to a degree that was greater than daily injections of gabapentin in rats. Diabetic mice that developed thermal hyperalgesia also responded to GAD65 or endomorphin gene delivery. The results suggest that either GAD65 or GAD67 vectors are the most effective in the treatment of diabetic pain. The vector combinations, GAD67+endomorphin, GAD67+enkephalin or endomorphin+enkephalin also produced a significant antinociceptive effect but the combination did not appear to be superior to single gene treatment. These findings provide further justification for the clinical development of antinociceptive gene therapies for the treatment of diabetic peripheral neuropathies.Gene Therapy advance online publication, 13 December 2012; doi:10.1038/gt.2012.90.
    Gene therapy 12/2012; · 4.75 Impact Factor
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    ABSTRACT: Glioblastoma tumors are highly invasive; therefore the overall prognosis of patients remains poor, despite major improvements in treatment techniques. Cancer cells detach from the inner tumor core and actively migrate away [1]; eventually these invasive cells might form clusters, which can develop to recurrent tumors. In vitro experiments in collagen gel [1] followed the clustering dynamics of different glioma cell lines. Based on the experimental data, we formulated a stochastic model for cell dynamics, which identified two mechanisms of clustering. First, there is a critical value of the strength of adhesion; above the threshold, large clusters grow from a homogeneous suspension of cells; below it, the system remains homogeneous, similarly to the ordinary phase separation. Second, when cells form a cluster, there is evidence that their proliferation rate increases. We confirmed the theoretical predictions in a separate cell migration experiment on a substrate and found that both mechanisms are crucial for cluster formation and growth [2]. In addition to their medical importance, these phenomena present exciting examples of pattern formation and collective cell behavior in intrinsically non-equilibrium systems [3]. [4pt] [1] A. M. Stein et al, Biophys. J., 92, 356 (2007). [0pt] [2] E. Khain et al, EPL 88, 28006 (2009). [0pt] [3] E. Khain et al, Phys. Rev. E. 83, 031920 (2011).
    02/2012;
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    ABSTRACT: PTEN (Phosphatase and tensin homolog deleted on chromosome 10) expression in stromal fibroblasts suppresses epithelial mammary tumours, but the underlying molecular mechanisms remain unknown. Using proteomic and expression profiling, we show that Pten loss from mammary stromal fibroblasts activates an oncogenic secretome that orchestrates the transcriptional reprogramming of other cell types in the microenvironment. Downregulation of miR-320 and upregulation of one of its direct targets, ETS2 (v-ets erythroblastosis virus E26 oncogene homolog 2) are critical events in Pten-deleted stromal fibroblasts responsible for inducing this oncogenic secretome, which in turn promotes tumour angiogenesis and tumour-cell invasion. Expression of the Pten-miR-320-Ets2-regulated secretome distinguished human normal breast stroma from tumour stroma and robustly correlated with recurrence in breast cancer patients. This work reveals miR-320 as a critical component of the Pten tumour-suppressor axis that acts in stromal fibroblasts to reprogramme the tumour microenvironment and curtail tumour progression.
    Nature Cell Biology 12/2011; 14(2):159-67. · 20.76 Impact Factor
  • Cancer Research 07/2011; 71(8 Supplement):1433-1433. · 8.65 Impact Factor
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    ABSTRACT: The systemic administration of oncolytic virus (OV) is often inefficient due to clearance of the virus by host defense mechanism and spurious targeting of non-cancer tissues through the bloodstream. Cell mediated OV delivery could hide the virus from host defenses and direct them toward tumors: Mesenchymal and neural stem cells have been described to possess tumor-homing ability as well as the capacity to deliver OVs. In this review, we will focus on approaches where OV and carrier cells are utilized for cancer therapy. Effective cellular internalization and replication of OVs need to occur both in cancer and carrier cells. We thus will discuss the current challenges faced by the use of OV delivery via carrier cells.
    Cytokine & growth factor reviews 03/2010; 21(2-3):119-26. · 6.49 Impact Factor
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    ABSTRACT: We investigate clustering of malignant glioma cells. In vitro experiments in collagen gels identified a cell line that formed clusters in a region of low cell density, whereas a very similar cell line (which lacks an important mutation) did not cluster significantly. We hypothesize that the mutation affects the strength of cell-cell adhesion. We investigate this effect in a new experiment, which follows the clustering dynamics of glioma cells on a surface. We interpret our results in terms of a stochastic model and identify two mechanisms of clustering. First, there is a critical value of the strength of adhesion; above the threshold, large clusters grow from a homogeneous suspension of cells; below it, the system remains homogeneous, similarly to the ordinary phase separation. Second, when cells form a cluster, we have evidence that they increase their proliferation rate. We have successfully reproduced the experimental findings and found that both mechanisms are crucial for cluster formation and growth.
    EPL (Europhysics Letters) 11/2009; 88(2):28006. · 2.26 Impact Factor
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    ABSTRACT: Recent data draw close parallels between cancer, including glial brain tumors, and the biology of stem and progenitor cells. At the same time, it has become clear that one of the major roles that microRNAs play is in the regulation of stem cell biology, differentiation, and cell 'identity'. For example, microRNAs have been increasingly implicated in the regulation of neural differentiation. Interestingly, initial studies in the incurable brain tumor glioblastoma multiforme strongly suggest that microRNAs involved in neural development play a role in this disease. This encourages the idea that certain miRs allow continued tumor growth through the suppression of differentiation and the maintenance of the stem cell-like properties of tumor cells. These concepts will be explored in this article.
    Cell death and differentiation 07/2009; 17(2):221-8. · 8.24 Impact Factor
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    M Aghi, T Visted, R A Depinho, E A Chiocca
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    ABSTRACT: Oncolytic herpes simplex viruses (HSVs), in clinical trials for the treatment of malignant gliomas, are assumed to be selective for tumor cells because their replication is strongly attenuated in quiescent cells, but not in cycling cells. Oncolytic selectivity is thought to occur because mutations in viral ICP6 (encoding a viral ribonucleotide reductase function) and/or gamma34.5 function are respectively complemented by mammalian ribonucleotide reductase and GADD34, whose genes are expressed in cycling cells. However, it is estimated that only 5-15% of malignant glioma cells are in mitosis at any one time. Therefore, effective replication of HSV oncolytic viruses might be limited to a subpopulation of tumor cells, since at any one time the majority of tumor cells would not be cycling. However, we report that an HSV with defective ICP6 function replicates in quiescent cultured murine embryonic fibroblasts obtained from mice with homozygous p16 deletions. Furthermore, intracranial inoculation of this virus into the brains of p16-/- mice provides evidence of viral replication that does not occur when the virus is injected into the brains of wild-type mice. These approaches provide in vitro and in vivo evidence that ICP6-negative HSVs are 'molecularly targeted,' because they replicate in quiescent tumor cells carrying specific oncogene deletions, independent of cell cycle status.
    Oncogene 08/2008; 27(30):4249-54. · 8.56 Impact Factor
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    ABSTRACT: An increasing number of oncolytic viruses have been developed and studied for cancer therapy. In response to needs for non-invasive monitoring and imaging of oncolytic virotherapy, several different approaches, including a positron emission tomography-based method, a method using secreted marker peptides, and optical imaging-based methods, have been reported. Among these modalities, we utilized the luciferase-based bioluminescent assay/imaging systems to determine the kinetics and dynamics of a productive viral infection. The replication cycle of herpes simplex virus type 1 (HSV-1) is punctuated by a temporal cascade of three classes of viral genes: immediate-early (IE), early (E) and late (L) genes. U(L)39- and gamma(1)34.5-deleted, replication-conditional HSV-1 mutants that express firefly luciferase under the control of the IE4/5 or strict-late gC promoters were generated. These oncolytic viruses were examined in cultured cells and a mouse tumor model. IE promoter- and strict-late promoter-mediated luciferase expression was confirmed to indicate viral infection and replication, respectively. Incorporation of a strict-late promoter-driven luciferase cassette into oncolytic HSV-1 vectors would be useful for assessing tumor oncolysis in preclinical tumor treatment studies.
    Gene Therapy 01/2007; 13(24):1731-6. · 4.32 Impact Factor
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    ABSTRACT: Glioblastoma is the most malignant form of brain cancer. It is extremely invasive; the mechanisms that govern invasion are not well understood. To better understand the process of invasion, we conducted an in vitro experiment in which a 3d tumour spheroid is implanted into a collagen gel. The paths of individual invasive cells were tracked. These cells were modeled as radially biased, persistent random walkers. The radial velocity bias was found to be 20 microns/hr on day one, but decayed significantly by day two. The cause of this bias is thought to be due to chemotactic factors and contact guidance along collagen fibers.
    11/2006;
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    ABSTRACT: Replication-conditional herpes simplex virus (HSV)-based vectors have great potential in the treatment of various types of cancers including brain tumors. HSV mutants lacking the U(L)39 gene and both copies of the gamma(1)34.5 gene (e.g. MGH1, G207) have been demonstrated to possess oncolytic effects as well as potent anticancer vaccination effects without compromising safety. Such mutants thus provide optimal templates to produce novel oncolytic HSV vectors for cancer gene therapy applications. In order to accomplish quick and efficient construction of oncolytic HSV vectors, a novel BAC-based method designated as 'HSVQuik system' was developed. This system sequentially utilizes two different site-specific recombination systems to introduce virtually any transgene cassettes of interest into the deleted U(L)39 locus (Flp-FRT in Escherichia coli) and to release the vector genome sequence from the procaryotic plasmid backbone (Cre-loxP in Vero cells). Taking advantage of the HSVQuik system, we constructed three oncolytic HSV vectors that express mouse IL4, CD40 ligand and 6CK, respectively. In vivo therapeutic experiments using two luciferase-labeled syngeneic mouse brain tumor models revealed that expression of these immunomodulators significantly enhanced antitumor efficacy of oncolytic HSV. The HSVQuik system, together with luciferase-labeled tumor models, should expedite the process of generating and evaluating oncolytic HSV vectors for cancer gene therapy applications.
    Gene Therapy 05/2006; 13(8):705-14. · 4.32 Impact Factor
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    S E Lawler, P P Peruzzi, E A Chiocca
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    ABSTRACT: Gene therapy is a potentially useful approach in the treatment of human brain tumors, which are notoriously refractory to conventional approaches. Most human clinical trials to date have been unsuccessful in terms of improving patient outcome. Recent improvements in viral vectors, the development of stem cell technology, and increased understanding of the mechanism of action of therapeutic transgenes provide hope that the next generation of gene therapeutics may show increased efficacy in treatment of this devastating disease.
    Cancer Gene Therapy 04/2006; 13(3):225-33. · 2.95 Impact Factor
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    ABSTRACT: PURPOSE: Attenuated Herpes simplex virus (HSV) mutants are being actively pursued for cancer therapy. rRp450 is derived from the HSV-1 strain KOS, but is deleted for the UL39 gene (encoding ICP6, the large subunit of ribonucleotide reductase) and replaced by the rat CYP2B1 gene (encoding a cytochrome P450 enzyme that activates oxazophosphorines, e.g. cyclophosphamide). While cyclophosphamide has been shown to enhance antitumor efficacy of rRp450, safety studies of the combination have not been reported. We tested rRp450 for virus attenuation in primary cells and for toxicity in FVB/N mice following intratumoral, intravenous and intracerebral administration alone or in combination with systemic cyclophosphamide.METHODS: Normal human primary cells were infected with rRp450 or wild-type KOS and virus production measured. FVB/N mice were administered 10^8 pfu rRp450 by intratumoral, intravenous and intracerebral routes alone or in combination with intraperitoneal cyclophosphamide at 50 or 200 mg/kg. Blood was collected to determine early (3 days) and late (28 days) effects on bone marrow function, liver function and renal function. Mice were also followed for survival. Wild-type KOS was administered to validate the susceptibility of FVB/N mice to HSV-1 infection.RESULTS: Relative to wild-type, replication of rRp450 wasattenuated by 3–4 orders of magnitude in primary human hepatocytes, differentiated primary human foreskin keratinocytes and differentiated primary human Schwann cells. Whereas intravenous wild-type virus was uniformly neurotoxic at 10^5 pfu and fatal at 10^6 pfu, and intracerebral virus was 80% and 100% fatal at 10^4 pfu and 10^5 pfu, respectively, intravenous and intracerebral rRp450 at 108 pfu was well tolerated. The combination of intravenous or intracerebral rRp450 with systemic cyclophosphamide was also without untoward effects. Intratumoral or intravenous rRp450, alone or in combination with cyclophosphamide, had no clinically significant effects on blood counts, serum electrolytes, liver function or kidney function compared with cyclophosphamide alone.CONCLUSIONS: In vitro replication studies suggest rRp450 is attenuated by 3–4 orders of magnitude. The FVB/N mouse is highly susceptible to wild type HSV-1 and is therefore a relevant model for preclinical toxicology of HSV-1 mutants. The virus rRp450, expressing the CYP2B1 gene product, was safe at the highest dose tested of 10^8 pfu by intravenous, intracerebral, and intratumoral administration. There were no additional toxicities of combination virus plus cyclophosphamide compared with cyclophosphamide alone. These data suggest the rRp450/prodrug combination is safe for testing in early phase human clinical trials.
    Molecular Therapy 01/2006; 13. · 7.04 Impact Factor
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    ABSTRACT: The neurofibromatoses are a diverse group of genetic conditions that share a predisposition to the development of tumors of the nerve sheath. Schwannomatosis is a recently recognized third major form of neurofibromatosis (NF) that causes multiple schwannomas without vestibular tumors diagnostic of NF2. Patients with schwannomatosis represent 2.4 to 5% of all patients requiring schwannoma resection and approximately one third of patients with schwannomatosis have anatomically localized disease with tumors limited to a single limb or segment of spine. Epidemiologic studies suggest that schwannomatosis is as common as NF2, but that familial occurrence is inexplicably rare. Patients with schwannomatosis overwhelmingly present with pain, and pain remains the primary clinical problem and indication for surgery. Diagnostic criteria for schwannomatosis are needed for both clinicians and researchers, but final diagnostic certainly will await the identification of the schwannomatosis locus itself.
    Neurology 07/2005; 64(11):1838-45. · 8.30 Impact Factor
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    ABSTRACT: The expression of genes from genomic loci can be relatively complex, utilizing exonic, intronic and flanking sequences to regulate tissue and developmental specificity. Infectious bacterial artificial chromosomes (iBACs) have been shown to deliver and express large genomic loci (up to 135 kb) into primary cells for functional analyses. The delivery of large genomic DNA inserts allows the expression of complex loci and of multiple splice variants. Herein, we demonstrate for the first time that an iBAC will deliver and correctly express in human glioma cells the entire CDKN2A/CDKN2B genomic region, which encodes for at least three important cell-cycle regulatory proteins (p16(INK4a), p14(ARF) and p15(INK4b)). Two of these proteins are expressed from overlapping genes, utilizing alternative splicing and promoter usage. The delivered locus expresses each gene at physiological levels and cellular responses (apoptosis versus growth arrest) occur dependent on cellular p53 status, as expected. The work further demonstrates the potential of the iBAC system for the delivery of genomic loci whose expression is mediated by complex splicing and promoter usage both for gene therapy applications and functional genomics studies.
    Gene Therapy 09/2004; 11(15):1195-204. · 4.32 Impact Factor
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    ABSTRACT: Functional analysis of large genomic loci in cell culture is extremely difficult to perform as genomic DNA transfer to primary cells, such as neurons, is nearly impossible by conventional means. We have developed an efficient infectious genomic DNA delivery vector called the infectious bacterial artificial chromosome, or iBAC, based on the herpes simplex virus type 1 (HSV-1) amplicon. We are applying the system to the analysis of two loci involved in genetic susceptibility to neurodegenerative disease, the microtubule associated protein tau (MAPT, or tau) locus and the α-synuclein (SNCA, or α-syn) locus.Three features make the vector well suited: i) the high capacity of HSV-1 amplicons allows us to package the entire tau or SNCA locus; ii) the neurotropism of HSV-1 amplicons ensures efficient gene delivery to primary neuronal cultures; iii) we can use BAC manipulation by homologous recombination to introduce mutations and polymorphisms for analysis.The tau protein is the major component of neurofibrillary tangles found in a range of neurodegenerative disorders, including Alzheimer's disease, frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Association studies have established a genetic link between the tau locus and PSP and CBD. The human tau locus lies on 17q21 and consists of 16 exons spanning 135 kb. Alternative splicing of exon 10 leads to a protein containing either three (3R; exon 10-) or four (4R; exon 10+) tandem repeats of a microtubule-binding motif. The regulation of exon 10 splicing control may underlie susceptibility to disease. To study tau splicing control we have constructed an iBAC vector carrying a 143 kb tau locus. The vector is packaged using an improved helper-virus free packaging system to titers of 2-3 × 107 transducing units/ml, and we obtain efficient vector delivery to primary neuronal cultures prepared from tau−/− mice. We are now analyzing expression from the iBAC-tau vector.Parkinson's Disease (PD) is the second most common neurodegenerative disease and affects about 1% of the Western population over 50 years of age. The specific neuropathological feature of PD is the formation of Lewy bodies, cytoplasmic protein aggregations composed mainly of α-synuclein found within affected neurons of the substantia nigra. SNCA mutations are found in rare forms of inherited autosomal dominant PD. However, the majority of PD cases have no mutations in the α-synuclein gene yet have α-synuclein protein deposits in Lewy bodies. Studies have shown an association of specific alleles of the SNCA locus, which differ in regulatory elements, with sporadic PD, and recent reports have shown triplication of the normal SNCA locus can cause PD. It seems likely that expression control of the SNCA locus will affect susceptibility to sporadic PD. The human SNCA locus contains 6 exons and spans 112 kb. We are building wild-type and recombinant iBAC-SNCA vectors to investigate the effect of sequence variation on the regulation of SNCA expression.The work exploits the high capacity and neurotropism of HSV-1 as a novel tool to study neurodegenerative disease.
    Molecular Therapy 01/2004; · 7.04 Impact Factor
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    ABSTRACT: Introduction.Herpes simplex virus (HSV) amplicon vector is a plasmid-based expression vector with the HSV infectivity. The vector system possesses a number of uniques features, including its large transgene capacity of up to 150 kb, its wide range of infectivity, and the ease and simplicity of its construction and packaging. In order to utilize these benefits of HSV amplicon, especially its large transgene capacity that enables infectious delivery of multiple transgenes and a large genomic transgene, the development of an strategy to achieve efficient transduction of amplicons into HSV resistant cells is indispensable. However, the structure and function of HSV glycoproteins are complicated for genetic modification, and targeting of HSV seems to be difficult. Recent studies have shown that HSV gD receptors, HveA and HveC, play a crucial role in HSV entry. It would be beneficial if we could convert HSV resistant cells to HSV sensitive cells in a short period of time by over-expressing these receptors. For this purpose, Adenoviral vector (AdV) is one of the promising candidates. AdV has various advantages over the other viral vectors: very high titers; highly purified vector stocks; transduce both dividing and non-dividing cells; and targeting by genetic modification of the viral fiber.We have recently developed a rapid and efficient system (designated as “AdQuik System”) to generate AdV. And now, we apply this technology for the rapid conversion of HSV resistant cells to sensitive cells.Purpose. Evaluation of AdV created by the AdQuik System.Determine whether AdV-mediated overexpression of HveA and HveC can improve transduction efficiency of HSV amplicons to HSV resistant cells.Materials and Methods.Cell lines: CHO cells and D74 glioma cellsAdV: AdQGC-HveA (expressing HveA and GFP), AdQGC-HveC (HveC and GFP). For control vectors, AdQGC-Luc (Luciferase and GFP) and AdQGC-LacZ (LacZ and GFP) were generated. An HSV-amplicon with RFP gene as a marker (RFP-amplicon) was generated. For in vitro study, cells were transduced with AdV 2 days before amplicon infection, and transduction efficiency of amplicon was examined 2 days after the infection under fluorescent microscope. For in vivo study, D74 cells were stereotactically inoculated to athymic mice in the brain. AdV and amplicons were injected after 7 days and 9 days after tumor inoculation, respectively. The mice were sacrificed 2days after the amplicon injection, and the brains were removed for histological examinations.Results.AdQGC-Luc and AdQGC-LacZ did not modify efficiency of amplicon transduction, and all GFP-positive cells with either of HSV receptors became positive for RFP in vitro. No significant difference of HSV infectivity was observed among the cells transfected with AdQGC-HveA, AdQGC-HveC, or AdQGC-HveA plus AdQGC-HveC. Histological studies of mouse brain samples also demonstrated the improvement of amplicon infectivity after pre-injection of either AdQGC-HveA or AdQGC-HveC.Conclusion.Replication-deficient AdV generated by the AdQuik system can be useful gene transfer vectors both in vitro and in vivo. AdV-mediated overexpression of the HSV receptors (HveA and HveC) improved transduction efficiency of HSV amplicons both in vitro and in vivo.
    Molecular Therapy 01/2004; 9. · 7.04 Impact Factor

Publication Stats

4k Citations
533.51 Total Impact Points

Institutions

  • 1999–2013
    • Brigham and Women's Hospital
      • Department of Neurosurgery
      Boston, Massachusetts, United States
  • 2006–2012
    • The Ohio State University
      • Department of Neurological Surgery
      Columbus, OH, United States
  • 2010
    • Comprehensive Cancer Centers of Nevada
      Las Vegas, Nevada, United States
  • 1990–2008
    • Massachusetts General Hospital
      • • Department of Neurosurgery
      • • Molecular Neurobiology Laboratory
      • • Department of Neurology
      • • Department of Surgery
      • • Department of Pathology
      Boston, MA, United States
  • 2001
    • Barrow Neurological Institute
      Phoenix, Arizona, United States
  • 2000–2001
    • Princeton University
      • Department of Chemical and Biological Engineering
      Princeton, NJ, United States
  • 1990–2001
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 1998–1999
    • Martin Luther University of Halle-Wittenberg
      Halle-on-the-Saale, Saxony-Anhalt, Germany
    • Università degli Studi di Genova
      Genova, Liguria, Italy