Research Topics
Species | Hiroyuki NakaiSummaryAffiliation: University of Pittsburgh Country: USA Publications
Research Grants
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Detail Information
Publications
Frequency and spectrum of genomic integration of recombinant adeno-associated virus serotype 8 vector in neonatal mouse liverKatsuya Inagaki
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, W1244 BSTWR, 200 Lothrop Street, Pittsburgh, PA 15261, USA
J Virol 82:9513-24. 2008..Further studies are warranted to elucidate the relationship between vector dose and integration frequency or spectrum...- The role of DNA-PKcs and artemis in opening viral DNA hairpin termini in various tissues in miceKatsuya Inagaki
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, W1244 BSTWR, 200 Lothrop St, Pittsburgh, PA 15261, USA
J Virol 81:11304-21. 2007..Thus, our approach furthers our understanding of not only rAAV biology but also fundamental DNA repair systems in various tissues of living animals... - DNA palindromes with a modest arm length of greater, similar 20 base pairs are a significant target for recombinant adeno-associated virus vector integration in the liver, muscles, and heart in miceKatsuya Inagaki
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, W1244 BSTWR, 200 Lothrop St, Pittsburgh, PA 15261, USA
J Virol 81:11290-303. 2007.... - A potential role of distinctively delayed blood clearance of recombinant adeno-associated virus serotype 9 in robust cardiac transductionNicole M Kotchey
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15219, USA
Mol Ther 19:1079-89. 2011.... - Robust systemic transduction with AAV9 vectors in mice: efficient global cardiac gene transfer superior to that of AAV8Katsuya Inagaki
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
Mol Ther 14:45-53. 2006..0 x 10(11) particles per mouse. Thus rAAV9, as well as rAAV8, is a robust vector for gene therapy applications and rAAV9 is superior to rAAV8 specifically for cardiac gene delivery by systemic vector administration... - The host response to adenovirus, helper-dependent adenovirus, and adeno-associated virus in mouse liverAnton P McCaffrey
Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242, USA
Mol Ther 16:931-41. 2008..Our results indicate that recognition of the Ad capsid or double-stranded DNA (of nonviral origin) in the vector elicits a robust type I IFN response that is, however, not elicited by AAV-derived vector transduction... - Liver transduction with recombinant adeno-associated virus is primarily restricted by capsid serotype not vector genotypeDirk Grimm
Department of Pediatrics and Genetics, School of Medicine, Stanford University, Room G305, 300 Pasteur Drive, Stanford, CA 94305, USA
J Virol 80:426-39. 2006..This corroborates our current model for AAV vector persistence in the liver and provides useful information for the future design and application of recombinant AAV... - A limited number of transducible hepatocytes restricts a wide-range linear vector dose response in recombinant adeno-associated virus-mediated liver transductionHiroyuki Nakai
Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA
J Virol 76:11343-9. 2002..Such information may be useful to determine appropriate vector doses for in vivo administration and provides further insights into the mechanisms of rAAV transduction in the liver... - Unrestricted hepatocyte transduction with adeno-associated virus serotype 8 vectors in miceHiroyuki Nakai
Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA
J Virol 79:214-24. 2005..In addition, the rAAV8 vector may offer a potential therapeutic agent for various diseases affecting nonhepatic tissues, but great caution is required for vector spillover and tight control of tissue-specific gene expression... - AAV serotype 2 vectors preferentially integrate into active genes in miceHiroyuki Nakai
Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Dr. Rm G305A, Stanford, California 94305, USA
Nat Genet 34:297-302. 2003.... - Helper-independent and AAV-ITR-independent chromosomal integration of double-stranded linear DNA vectors in miceHiroyuki Nakai
Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA
Mol Ther 7:101-11. 2003..In addition, they may provide a clue for developing new nonviral integrating gene delivery vector systems... - Pathways of removal of free DNA vector ends in normal and DNA-PKcs-deficient SCID mouse hepatocytes transduced with rAAV vectorsHiroyuki Nakai
Departments of Pediatrics and Genetics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA
Hum Gene Ther 14:871-81. 2003..These studies shed new light on the molecular mechanisms of rAAV vector transduction in vivo... - Recombinant adeno-associated virus type 8-mediated extensive therapeutic gene delivery into skeletal muscle of alpha-sarcoglycan-deficient miceAkiyo Nishiyama
Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187 8502, Japan
Hum Gene Ther 19:719-30. 2008..This extensive rAAV8-mediated alpha-SG transduction in LGMD 2D model animals paves the way for future clinical application... - Free DNA ends are essential for concatemerization of synthetic double-stranded adeno-associated virus vector genomes transfected into mouse hepatocytes in vivoHiroyuki Nakai
Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA
Mol Ther 7:112-21. 2003..Based on these observations, we propose a model whereby ds linear molecules with free DNA ends, but not circular molecules, play an important role in rAAV vector genome concatemerization... - Inhibition of hepatitis B virus in mice by RNA interferenceAnton P McCaffrey
Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, Room G305, Stanford, California, USA
Nat Biotechnol 21:639-44. 2003..Thus, RNAi effectively inhibited replication initiation in cultured cells and mammalian liver, showing that such an approach could be useful in the treatment of viral diseases... - Large-scale molecular characterization of adeno-associated virus vector integration in mouse liverHiroyuki Nakai
Department of Pediatrics, 300 Pasteur Dr, Grant Bldg, Rm S374, Stanford University School of Medicine, Stanford, CA 94305, USA
J Virol 79:3606-14. 2005..Thus, the present study provides new insights into the risk of rAAV-mediated insertional mutagenesis and the mechanisms of rAAV integration... - Preclinical in vivo evaluation of pseudotyped adeno-associated virus vectors for liver gene therapyDirk Grimm
Department of Pediatrics, School of Medicine, Stanford University, Stanford, CA, USA
Blood 102:2412-9. 2003..Our technology and findings should facilitate the development of AAV pseudotype-based gene therapies for hemophilia B and other liver-related diseases... - Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune responseCatherine S Manno
The Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, Pennsylvania, 19104, USA
Nat Med 12:342-7. 2006..We conclude that rAAV-2 vectors can transduce human hepatocytes in vivo to result in therapeutically relevant levels of F.IX, but that future studies in humans may require immunomodulation to achieve long-term expression... - Looking into the safety of AAV vectorsMark A Kay
Nature 424:251. 2003 - Modified infusion procedures affect recombinant adeno-associated virus vector type 2 transduction in the liverKazuo Ohashi
Program in Human Gene Therapy, Departments of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305-5208, USA
Hum Gene Ther 16:299-306. 2005..In all, the present study clearly demonstrated that hepatic arterial infusion of rAAV is effective for liver-directed gene therapy and that other parameters related to blood flow can be adjusted to further optimize gene transfer...
Research Grants
- Establishment of the Risk of AAV Vector IntegrationHiroyuki Nakai; Fiscal Year: 2005..abstract_text> ..
- Vector and host cellular biology in AAV vector transduction in vivoHiroyuki Nakai; Fiscal Year: 2007..The proposed project should substantially contribute to building an intellectual foundation for successful human gene therapy. ..
- Vector and host cellular biology in AAV vector transduction in vivoHiroyuki Nakai; Fiscal Year: 2010..Results of the study will contribute to designing and developing more efficient and safer rAAV vectors and assessing the safety of the vector. ..