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| Mark KaySummaryAffiliation: Stanford University Country: USA Publications
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Publications
Viral vectors for gene therapy: the art of turning infectious agents into vehicles of therapeuticsM A Kay
Departments of Pediatrics and Genetics, Stanford University, Stanford, CA, USA
Nat Med 7:33-40. 2001..While substantial progress has been made, and some clinical successes are over the horizon, further vector refinement and/or development is required before gene therapy will become standard care for any individual disorder...- State-of-the-art gene-based therapies: the road aheadMark A Kay
Department of Pediatrics and Genetics, Stanford University, 269 Campus Drive, Room 2105, Stanford, California 94305, USA
Nat Rev Genet 12:316-28. 2011..However, recent progress in the field is finally realizing some of the promises made more than 20 years ago, providing optimism for additional successes in the near future... - AAV vectors and tumorigenicityMark A Kay
Department of Pediatrics, Rm G305, Stanford University, Stanford, California 94305, USA
Nat Biotechnol 25:1111-3. 2007 - How do miRNAs mediate translational repression?Shuo Gu
Departments of Pediatrics and Genetics, Stanford University, Stanford, CA 94305, USA
Silence 1:11. 2010..In this paper, we focus on possible explanations for the various interpretations of these data sets, and provide a model that we believe is consistent with many of the observations published to date... - An in vitro-identified high-affinity nucleosome-positioning signal is capable of transiently positioning a nucleosome in vivoLia E Gracey
Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA
Epigenetics Chromatin 3:13. 2010.... - A robust system for production of minicircle DNA vectorsMark A Kay
Department of Pediatrics and Genetics, Stanford University School of Medicine, Stanford, California, USA
Nat Biotechnol 28:1287-9. 2010..This bacterial strain produces purified minicircles in a time frame and quantity similar to those of routine plasmid DNA preparation, making it feasible to use minicircles in place of plasmids in mammalian transgene expression studies... - 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... - 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.... - Rapid uncoating of vector genomes is the key to efficient liver transduction with pseudotyped adeno-associated virus vectorsClare E Thomas
Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA
J Virol 78:3110-22. 2004..Our data suggest that the rate of uncoating of vector genomes determines the ability of complementary plus and minus single-stranded genomes to anneal together and convert to stable, biologically active double-stranded molecular forms... - 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... - 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... - Epstein-Barr virus vectors provide prolonged robust factor IX expression in miceChristopher R Sclimenti
Department of Genetics, Stanford University School of Medicine, California 94305, USA
Biotechnol Prog 19:144-51. 2003..These results underline the crucial importance of appropriate gene expression signals on gene therapy vectors and the utility of EBV sequences in particular for increasing stable gene expression... - 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... - Characterization of the relationship of AAV capsid domain swapping to liver transduction efficiencyXuan Shen
Department of Pediatrics, Stanford University, Stanford, California 94305, USA
Mol Ther 15:1955-62. 2007.... - 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... - 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... - Expression of shRNA from a tissue-specific pol II promoter is an effective and safe RNAi therapeuticJeffery C Giering
Department of Pediatrics, Stanford University, Stanford, California 94305, USA
Mol Ther 16:1630-6. 2008.... - Comparison of adenoviral and adeno-associated viral vectors for pancreatic gene delivery in vivoAlfred Y Wang
Department of Molecular Pharmacology, School of Medicine, Stanford University, Stanford, CA 94305, USA
Hum Gene Ther 15:405-13. 2004..These vectors will be useful for studying novel gene delivery based treatments in animal models for diabetes and other pancreatic disorders... - In vitro and in vivo gene therapy vector evolution via multispecies interbreeding and retargeting of adeno-associated virusesDirk Grimm
Department of Pediatrics, School of Medicine, Stanford University, Stanford, CA 94305, USA
J Virol 82:5887-911. 2008..Our study validates DNA family shuffling and viral peptide display as two powerful and compatible approaches to the molecular evolution of novel AAV vectors for human gene therapy applications... - A new adenoviral helper-dependent vector results in long-term therapeutic levels of human coagulation factor IX at low doses in vivoAnja Ehrhardt
Department of Pediatrics and Genetics, School of Medicine, Stanford University, CA 94305, USA
Blood 99:3923-30. 2002.... - 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... - Helper virus-free, optically controllable, and two-plasmid-based production of adeno-associated virus vectors of serotypes 1 to 6Dirk Grimm
Department of Pediatrics and Department of Genetics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, USA
Mol Ther 7:839-50. 2003..In sum, the HOT strategy and the antibodies presented here, together with the reported findings, should facilitate and support the further development of AAV serotype vectors as powerful new tools for human gene therapy... - High-resolution genome-wide mapping of transposon integration in mammalsStephen R Yant
Stanford University School of Medicine, Department of Pediatrics, 300 Pasteur Dr, Room G-305, Stanford, CA 94305-5208, USA
Mol Cell Biol 25:2085-94. 2005..These findings provide basic insights into the transposition process and reveal important distinctions between transposon- and virus-based integrating vectors... - A two-hybrid screen identifies cathepsins B and L as uncoating factors for adeno-associated virus 2 and 8Bassel Akache
Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305 5208, USA
Mol Ther 15:330-9. 2007.... - Progress and problems with the use of viral vectors for gene therapyClare E Thomas
Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA
Nat Rev Genet 4:346-58. 2003..With the development of a leukaemia-like syndrome in two of the small number of patients that have been cured of a disease by gene therapy, it is timely to contemplate how far this technology has come, and how far it still has to go... - A direct comparison of two nonviral gene therapy vectors for somatic integration: in vivo evaluation of the bacteriophage integrase phiC31 and the Sleeping Beauty transposaseAnja Ehrhardt
Department of Pediatrics, School of Medicine, Stanford University, 300 Pasteur Drive, Stanford, CA 94305, USA
Mol Ther 11:695-706. 2005..Coupled together with ongoing improvements in both systems this study suggests that both nonviral vector systems will have important roles in achieving stable gene transfer in vivo... - 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... - Optimization of cis-acting elements for gene expression from nonviral vectors in vivoAnja Ehrhardt
Departments of Pediatrics and Genetics, School of Medicine, Stanford University, Stanford, CA 94305, USA
Hum Gene Ther 14:215-25. 2003.... - 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... - Adenovirus transduction is required for the correction of diabetes using Pdx-1 or Neurogenin-3 in the liverAlfred Y Wang
Department of Molecular Pharmacology, School of Medicine, Stanford University, Stanford, California 94305, USA
Mol Ther 15:255-63. 2007..Our results suggest that a host response to adenovirus in combination with expression of a pro-endocrine pancreas transcription factor is sufficient to induce insulin production in the livers of diabetic mice... - Episomal persistence of recombinant adenoviral vector genomes during the cell cycle in vivoAnja Ehrhardt
Department of Pediatrics and Genetics, School of Medicine, Stanford University, Stanford, California 94305, USA
J Virol 77:7689-95. 2003..Several potential mechanisms are proposed... - AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia BCatherine S Manno
Department of Pediatrics, University of Pennsylvania and The Children s Hospital of Philadelphia, PA, 19104, USA
Blood 101:2963-72. 2003.... - Role of hepatocyte direct hyperplasia in lentivirus-mediated liver transduction in vivoKazuo Ohashi
Department of Pediatrics, Stanford University, Stanford, CA 94305, USA
Hum Gene Ther 13:653-63. 2002..Taken together, this study suggests that disease-induced cellular proliferation in the liver will enhance the utility of this vector in treating diseases such as viral hepatitis, liver cirrhosis, and cancer... - Increased maintenance and persistence of transgenes by excision of expression cassettes from plasmid sequences in vivoEfren Riu
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Hum Gene Ther 16:558-70. 2005.... - Site-specific genomic integration produces therapeutic Factor IX levels in miceEric C Olivares
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA
Nat Biotechnol 20:1124-8. 2002..Integration was documented at two pseudo-attP sites, native sequences with partial identity to attP, with one site highly predominant. This study demonstrates in vivo gene transfer in an animal by site-specific genomic integration... - Novel minicircle vector for gene therapy in murine myocardial infarctionMei Huang
Department of Radiology, Stanford University School of Medicine, CA 94305 5344, USA
Circulation 120:S230-7. 2009..In this study, we develop a novel nonviral vector that robustly and persistently expresses the hypoxia-inducible factor-1 alpha (HIF-1alpha) therapeutic gene in the heart, leading to functional benefits after myocardial infarction... - Somatic integration from an adenoviral hybrid vector into a hot spot in mouse liver results in persistent transgene expression levels in vivoAnja Ehrhardt
Department of Pediatrics, School of Medicine, Stanford University, Stanford, California, USA
Mol Ther 15:146-56. 2007..With further optimization, this system represents a new tool for gene therapy protocols that may offer an alternative to gene therapy approaches based on random integrating viral vectors... - Molecular analysis of chromosomal rearrangements in mammalian cells after phiC31-mediated integrationAnja Ehrhardt
Department of Pediatrics, School of Medicine, Stanford University, Stanford, CA 94305, USA
Hum Gene Ther 17:1077-94. 2006.... - Histone modifications are associated with the persistence or silencing of vector-mediated transgene expression in vivoEfren Riu
Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA
Mol Ther 15:1348-55. 2007..Our data indicates that (i) episomal vectors undergo chromatinization in vivo, and (ii) both persistence and silencing of transgene expression are associated with specific histone modifications... - Postintegrative gene silencing within the Sleeping Beauty transposition systemBrian S Garrison
Stanford University School of Medicine, Department of Pediatrics, Stanford, CA 94305 5208, USA
Mol Cell Biol 27:8824-33. 2007..Collectively, these data reveal the existence of a multicomponent postintegrative gene silencing network that efficiently targets invading transposon sequences for transcriptional silencing in mammalian cells... - A gene-deleted adenoviral vector results in phenotypic correction of canine hemophilia B without liver toxicity or thrombocytopeniaAnja Ehrhardt
Department of Pediatrics, School of Medicine, Stanford University, Stanford, CA, USA
Blood 102:2403-11. 2003..Taken together, this study demonstrates that injection of an adenoviral HD vector results in complete but transient phenotypic correction of FIX deficiency in canine models with no detectable toxicity... - Adeno-associated virus vectors for short hairpin RNA expressionDirk Grimm
Department of Pediatrics, Stanford University, Stanford, CA 94305-5208, USA
Methods Enzymol 392:381-405. 2005..Our novel vector plasmids complement existing AAV vector technology and should help further establish AAV as a most promising alternative to using adeno- or retro-?lentiviral vectors as shRNA delivery vehicles... - Silencing of episomal transgene expression in liver by plasmid bacterial backbone DNA is independent of CpG methylationZhi Ying Chen
Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA
Mol Ther 16:548-56. 2008.... - Low-level shRNA cytotoxicity can contribute to MYC-induced hepatocellular carcinoma in adult miceShelly Beer
Department of Medicine, Division of Oncology, School of Medicine, Center for Clinical Sciences Research, Stanford University, Stanford, California 94305 5151, USA
Mol Ther 18:161-70. 2010..Our data warrant caution regarding the possible carcinogenic potential of shRNAs when used as clinical agent, particularly in circumstances where tissues are genetically predisposed to cellular transformation and proliferation... - Nonhomologous-end-joining factors regulate DNA repair fidelity during Sleeping Beauty element transposition in mammalian cellsStephen R Yant
Departments of Pediatrics and Genetics, Stanford University School of Medicine, Stanford, California 94305-5208, USA
Mol Cell Biol 23:8505-18. 2003..We conclude that, based on its ability to regulate excision site junctional diversity and transposon insertion frequency, DNA-PK serves an important protective role during transpositional recombination in mammals... - The 37/67-kilodalton laminin receptor is a receptor for adeno-associated virus serotypes 8, 2, 3, and 9Bassel Akache
Stanford University, Department of Pediatrics, 300 Pasteur Drive, Room G305, Stanford, CA 94305 5208, USA
J Virol 80:9831-6. 2006..Along with its robust transduction efficiency, our findings support the continued development of AAV8-based vectors for clinical applications in humans, especially for tumor gene therapy... - Advancing molecular therapies through in vivo bioluminescent imagingAnton McCaffrey
Stanford University, Stanford, CA, USA
Mol Imaging 2:75-86. 2003..BLI can be used to accelerate the evaluation of experimental therapeutic strategies and whole body imaging offers the opportunity of revealing the effects of novel approaches on key steps in disease processes... - Argonaute proteins are key determinants of RNAi efficacy, toxicity, and persistence in the adult mouse liverDirk Grimm
Stanford University School of Medicine, Department of Pediatrics, Center for Clinical Sciences and Research, Stanford, California, USA
J Clin Invest 120:3106-19. 2010..Our studies substantiate that abundant small RNAs can overload the endogenous RNAi pathway and reveal possible strategies for reducing hepatotoxicity of short- and long-term clinical gene silencing in humans... - A prenylation inhibitor prevents production of infectious hepatitis delta virus particlesBruno B Bordier
Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 269 Campus Drive, Palo Alto, CA 94305-5187, USA
J Virol 76:10465-72. 2002..Farnesyltransferase inhibitors thus represent an attractive potential class of novel antiviral agents for use against HDV, including the genotypes associated with most severe disease... - Site-directed transposon integration in human cellsStephen R Yant
Department of Pediatrics and Genetics, Stanford University School of Medicine, Stanford, CA 94305 5208, USA
Nucleic Acids Res 35:e50. 2007..These findings illustrate the feasibility of directed transposon integration and highlight potential means for future development... - A story of mice and menAnton P McCaffrey
Anton McCaffrey and Mark Kay are in the Program in Human Gene Therapy, Departments of Pediatrics and Genetics, Stanford University School of Medicine, Stanford, California 94305, USA
Gene Ther 9:1563. 2002 - A nonviral minicircle vector for deriving human iPS cellsFangjun Jia
Departments of Medicine and Radiology, Stanford University School of Medicine, Stanford, California, USA
Nat Methods 7:197-9. 2010..Here we use a single minicircle vector to generate transgene-free iPSCs from adult human adipose stem cells... - Transposition from a gutless adeno-transposon vector stabilizes transgene expression in vivoStephen R Yant
Department of Pediatrics and Genetics, Stanford University School of Medicine, Stanford, CA 94305-5208, USA
Nat Biotechnol 20:999-1005. 2002..These vectors combine the versatility of adenoviral vectors with the integration capabilities of a eukaryotic DNA transposon and should prove useful in the treatment of genetic diseases... - Hepatic parenchymal replacement in mice by transplanted allogeneic hepatocytes is facilitated by bone marrow transplantation and mediated by CD4 cellsKonrad L Streetz
Department of Pediatrics and Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA
Hepatology 47:706-18. 2008..CONCLUSION: The present mouse model provides a versatile platform for investigation of the mechanisms governing HT with direct relevance to the development of clinical strategies for the treatment of human hepatic failure... - Combinatorial RNAi: a winning strategy for the race against evolving targets?Dirk Grimm
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Mol Ther 15:878-88. 2007..Here, we critically review all coRNAi strategies and discuss the requirements for their transition into clinical application... - Sarcoma derived from cultured mesenchymal stem cellsJakub Tolar
Department of Pediatrics, Division of Hematology Oncology, Blood and Marrow Transplant and Cancer Center, University of Minnesota Medical School, Minneapolis, Minnesota, USA
Stem Cells 25:371-9. 2007..More importantly, our study indicates that sarcoma can evolve from MSC cultures... - Mutational analysis of the N-terminal DNA-binding domain of sleeping beauty transposase: critical residues for DNA binding and hyperactivity in mammalian cellsStephen R Yant
Stanford University, Department of Pediatrics, 300 Pasteur Dr, Room G305, Stanford, CA 94305-5208, USA
Mol Cell Biol 24:9239-47. 2004..These studies provide important insights into vertebrate transposon biology and indicate that Sleeping Beauty can be readily improved for enhanced genetic research applications in mammals... - Improved production and purification of minicircle DNA vector free of plasmid bacterial sequences and capable of persistent transgene expression in vivoZhi-Ying Chen
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Hum Gene Ther 16:126-31. 2005..8 mg of minicircle with 97% purity was prepared from a 1 liter bacterial culture. The high yield, simple purification, and robust and persistent transgene expression make these vectors viable for gene therapy applications... - Real-time in vivo imaging of stem cells following transgenesis by transpositionJakub Tolar
Department of Pediatrics, Division of Hematology, Oncology, Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN 55455, USA
Mol Ther 12:42-8. 2005..This novel dual-reporter imaging approach based on the transgenesis of MAPC with Sleeping Beauty transposons sheds light on the homing patterns of MAPC and paves the way for quantification of MAPC engraftment in real time in vivo... - Donor-derived, liver-specific protein expression after bone marrow transplantationD Denison Jenkins
Department of Surgery, Stanford University School of Medicine, Stanford, California 94305-5733, USA
Transplantation 78:530-6. 2004..Expression is low, but inducible with liver injury. We are currently developing strategies to augment donor-derived, liver-specific protein expression after BMT... - Helper-Independent Sleeping Beauty transposon-transposase vectors for efficient nonviral gene delivery and persistent gene expression in vivoJacob Giehm Mikkelsen
Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305-5208, USA
Mol Ther 8:654-65. 2003.... - Minicircle DNA vectors devoid of bacterial DNA result in persistent and high-level transgene expression in vivoZhi-Ying Chen
Department of Pediatrics and Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA
Mol Ther 8:495-500. 2003..Our data suggest that minicircles are capable of expressing high and persistent levels of therapeutic products in vivo and have a great potential to serve as episomal vectors for the treatment of a wide variety of diseases... - A potent and specific morpholino antisense inhibitor of hepatitis C translation in miceAnton P McCaffrey
Program in Human Gene Therapy, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Hepatology 38:503-8. 2003..Notably, the level of antisense inhibition observed in this in vivo model is similar to the maximal inhibition we have obtained previously with RNA interference in mice... - System for simultaneous tissue-specific and disease-specific regulation of therapeutic gene expressionYung H Chyung
Department of Pediatrics and Genetics, School of Medicine, Stanford University, Stanford, CA 94305, USA
Hum Gene Ther 14:1255-64. 2003..The improved regulation offered by our system would facilitate the targeting of transgene expression to sites of disease in the body and spare healthy tissue, thereby considerably enhancing the therapeutic window of gene therapy... - Liver tissue engineering at extrahepatic sites in mice as a potential new therapy for genetic liver diseasesKazuo Ohashi
Department of Pediatrics and Genetics, Stanford University Medical Center, Stanford, CA 94305-5208, USA
Hepatology 41:132-40. 2005..In conclusion, our studies indicate that liver tissues can be engineered and maintained at extrahepatic sites, retain their capacity for regeneration in vivo, and used to successfully treat genetic disorders... - 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... - The effect of age on hepatic gene transfer with self-inactivating lentiviral vectors in vivoFrank Park
Department of Medicine and Department of Pharmacology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
Mol Ther 8:314-23. 2003..In conclusion, the present study strongly demonstrates that lentiviral vector transduction efficiency and transgene expression were significantly enhanced in adolescent compared to older mice... - Looking into the safety of AAV vectorsMark A Kay
Nature 424:251. 2003 - Rapid and stable knockdown of an endogenous gene in retinal pigment epitheliumDaniel M Paskowitz
Beckman Vision Center, University of California, San Francisco, San Francisco, CA 94143, USA
Hum Gene Ther 18:871-80. 2007..Viral delivery of RNAi constructs offers a powerful and versatile approach for both gene therapy and the analysis of fundamental questions in retinal biology... - Radioprotection in vitro and in vivo by minicircle plasmid carrying the human manganese superoxide dismutase transgeneXichen Zhang
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
Hum Gene Ther 19:820-6. 2008..Intravenous, systemic administration of mc-MnSOD-PL protected mice from total body irradiation (9.75 Gy). Therefore, minicircle DNA containing the human MnSOD transgene confers undiminished radioprotection in vitro and in vivo... - 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... - 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... - 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... - Cis-acting gene regulatory activities in the terminal regions of sleeping beauty DNA transposon-based vectorsBrian Moldt
Department of Human Genetics, University of Aarhus, DK 8000 Aarhus, Denmark
Hum Gene Ther 18:1193-204. 2007..Our data suggest that SB-based gene vectors may carry ancient properties of self-regulation with potential relevance for SB-directed therapeutic gene transfer... - Host factors that impact the biodistribution and persistence of multipotent adult progenitor cellsJakub Tolar
Pediatric Hematology Oncology Blood and Marrow Transplantation Program, MMC 366, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455, USA
Blood 107:4182-8. 2006..Our data indicate that the biodistribution and persistence of reporter gene-labeled MAPCs are maximized after intra-arterial delivery or host irradiation and that T cells, B cells, and NK cells contribute to in vivo MAPC rejection... - In vivo correction of murine tyrosinemia type I by DNA-mediated transpositionEugenio Montini
Department of Medical and Molecular Genetics, Oregon Health and Sciences University, Portland, Oregon 97239, USA
Mol Ther 6:759-69. 2002..Molecular analysis indicated that high-efficiency DNA-mediated transposition into the mouse genome was strictly dependent on the expression of wild-type transposase... - 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.... - Prime time for small RNA-based therapeuticsMark A Kay
Hum Gene Ther 19:15-6. 2008
Research Grants
- Studies on RNAi Based Delivery in VivoMark Kay; Fiscal Year: 2007....
- RNAi for the Treatment of Viral HepatitisMark Kay; Fiscal Year: 2007..We believe the data generated during the granting period will develop the reagents necessary to pursue a Phase I clinical trial for HCV infection. ..
- RNAi for the Treatment of Viral HepatitisMark Kay; Fiscal Year: 2009..We believe the data generated during the granting period will develop the reagents necessary to pursue a Phase I clinical trial for HCV infection. ..
- Studies on RNAi Based Delivery in VivoMark Kay; Fiscal Year: 2009....
- HEPATIC GENE TRANSFER FOR TREATMENT OF HEMOPHILIAS A & BMark A Kay; Fiscal Year: 2010..Our studies will advance gene therapeutic approaches towards achieving a cure for the hemophilias. ..
- Molecular Evolution Strategies to Derive New Recombinant AAV VectorsMark A Kay; Fiscal Year: 2010..Once the new AAV vectors are created, they will be tested in animal models of human disease. ..
- Studies on RNAi Based Delivery in VivoMark A Kay; Fiscal Year: 2010..We are studying the role of that these RNAs might play in gene regulation and designing new strategies to develop these into novel therapeutic approaches to treat disease. ..
- RNAi for the Treatment of Viral HepatitisMark A Kay; Fiscal Year: 2010..We believe the data generated during the granting period will develop the reagents necessary to pursue a Phase I clinical trial for HCV infection. ..
- HEPATIC GENE TRANSFER FOR TREATMENT OF HEMOPHILIAS A & BMark A Kay; Fiscal Year: 2011..Our studies will advance gene therapeutic approaches towards achieving a cure for the hemophilias. ..
- Hepatic Gene Transfer for Treatment of Hemophilias A&BMark Kay; Fiscal Year: 2007..The studies outlined here will further our understanding of gene transduction and mechanisms of transgene expression as well as have direct applications for gene therapy for hemophilia. ..
- IMPROVED ADENOVIRAL VECTORS FOR HEPATIC GENE THERAPYMark Kay; Fiscal Year: 2002..The results of these studies will have important implications for the development of adenoviruses for gene therapy. ..
- HEPATIC GENE TRANSFER FOR TREATMENT OF HEMOPHILIAS A & BMark Kay; Fiscal Year: 2003..abstract_text> ..
- IMPROVED ADENOVIRAL VECTORS FOR HEPATIC GENE THERAPYMark Kay; Fiscal Year: 2006..Taken together, these studies will advance our basic understanding of vector-host interactions related to persistence of vector in rive, as well as advancing therapeutic applications in preclinical development. ..
- RNAi for the Treatment of Viral HepatitisMark A Kay; Fiscal Year: 2010..We believe the data generated during the granting period will develop the reagents necessary to pursue a Phase I clinical trial for HCV infection. ..