Cao, Dan, Haussecker, Dirk, Huang, Yong, Kay, Mark A.
Human hepatitis delta virus (HDV) is the only animal virus known to replicate its RNA genome using a host polymerase because its only virally encoded proteins, the small and large hepatitis delta...
Hiroyuki Nakai, Xiaolin Wu, Sally Fuess, Theresa A. Storm, David Munroe, Eugenio Montini, ...
Recombinant adeno-associated virus (rAAV) vector holds promise for gene therapy. Despite a low frequency of chromosomal integration of vector genomes, recent studies have raised concerns about the...
Site-directed transposon integration in human cells (2007)
Yant, Stephen R., Huang, Yong, Akache, Bassel, Kay, Mark A.
The Sleeping Beauty (SB) transposon is a promising gene transfer vector that integrates nonspecifically into host cell genomes. Herein, we attempt to direct transposon integration into predetermined...
Site-directed transposon integration in human cells (2007)
Yant, Stephen R., Huang, Yong, Akache, Bassel, Kay, Mark A.
The Sleeping Beauty (SB) transposon is a promising gene transfer vector that integrates nonspecifically into host cell genomes. Herein, we attempt to direct transposon integration into predetermined...
O'shaughnessy, Matthew J, Panoskaltsis-Mortari, Angela, McElmurry, Ron T, Bell, Scott, Riddle, Megan, ...
Multipotent adult progenitor cells (MAPCs) are marrow-derived pluripotent stem cells with a broad differentiation potential. We sought to identify factors that affect adoptively transferred MAPCs. In...
Real-time in vivo imaging of stem cells following transgenesis by transposition (2005)
Osborn, Mark, Bell, Scott, McElmurry, Ron, Xia, Lily, Riddle, Megan, ...
Previous studies have identified Sleeping Beauty transposons as efficient vectors for nonviral gene delivery in mammalian cells. However, studies demonstrating the usefulness of transposons as gene...
High-Resolution Genome-Wide Mapping of Transposon Integration in Mammals (2004)
Stephen R. Yant, Xiaolin Wu, Yong Huang, Brian Garrison, Shawn M. Burgess, Mark A. Kay
The Sleeping Beauty (SB) transposon is an emerging tool for transgenesis, gene discovery, and therapeutic gene delivery in mammals. Here we studied 1,336 SB insertions in primary and cultured...
In vivo activity of nuclease-resistant siRNAs (2004)
LAYZER, JULIANA M., MCCAFFREY, ANTON P., TANNER, ALICE K., HUANG, ZAN, KAY, MARK A., SULLENGER, BRUCE A.
Chemical modifications have been incorporated into short interfering RNAs (siRNAs) without reducing their ability to inhibit gene expression in mammalian cells grown in vitro. In this study, we begin...
Qian, Su, Zhang, Jing-Yu, Kay, Mark A., Jacobs-Lorena, Marcelo
The expression of ribosomal protein (r-protein) genes is uniquely regulated at the translational level during early development of Drosophila. Here we report results of a detailed analysis of the...
Kay, Mark A., Meuse, Leonard, Gown, Allen M., Linsley, Peter, Hollenbaugh, Diane, Aruffo, Alejandro, ...
Although recombinant adenovirus vectors offer a very efficient means by which to transfer genetic information into cells in vivo, antigen-dependent immunity limits the duration of gene expression and...
Kay, Mark A., Liu, Dexi, Hoogerbrugge, Peter M.
In recent years, there have been a number of technological breakthroughs that have allowed for clinical trials in gene therapy to be initiated. In combination with the genome initiative, the...
Correction of the retinal dystrophy phenotype of the RCS rat by viral gene transfer of Mertk
Vollrath, Douglas, Feng, Wei, Duncan, Jacque L., Yasumura, Douglas, D'Cruz, Patricia M., Chappelow, Aimee, ...
The Royal College of Surgeons (RCS) rat is a widely studied animal model of retinal degeneration in which the inability of the retinal pigment epithelium (RPE) to phagocytize shed photoreceptor outer...
Wilson, Christopher B., Embree, Lisa J., Schowalter, David, Albert, Richard, Aruffo, Alejandro, Hollenbaugh, Diane, ...
Recombinant adenovirus vectors have been used to transfer genes to the lungs in animal models, but the extent and duration of primary transgene expression and the ability to achieve expression after...
Lieber, André, He, Chen-Yi, Meuse, Leonard, Himeda, Charis, Wilson, Christopher, Kay, Mark A.
NF-κB is a key regulator of the innate antiviral immune response, due in part to its transcriptional activation of cytokines and adhesion molecules, which, in turn, function in chemotaxis and...
Lieber, André, Kay, Mark A., Li, Zong-Yi
Moloney murine leukemia virus (MoMLV)-derived vectors require cell division for efficient transduction, which may be related to an inability of the viral DNA-protein complex to cross the nuclear...
Miao, Carol H., Nakai, Hiroyuki, Thompson, Arthur R., Storm, Theresa A., Chiu, Winnie, Snyder, Richard O., ...
Recombinant adeno-associated virus vectors (rAAV) show promise in preclinical trials for the treatment of genetic diseases including hemophilia. Liver-directed gene transfer results in a slow rise in...
Nakai, Hiroyuki, Storm, Theresa A., Kay, Mark A.
Recombinant adeno-associated virus (rAAV) vectors stably transduce hepatocytes in experimental animals. Following portal-vein administration of rAAV vectors in vivo, single-stranded (ss) rAAV genomes...
Schowalter, David B., Himeda, Charis L., Winther, Brian L., Wilson, Christopher B., Kay, Mark A.
This study explores the genetic and immunologic factors involved in the differences in duration of transgene expression following in vivo transduction with recombinant adenoviruses. Different strains...
Isolation of Recombinant Adeno-Associated Virus Vector-Cellular DNA Junctions from Mouse Liver
Nakai, Hiroyuki, Iwaki, Yuichi, Kay, Mark A., Couto, Linda B.
Recombinant adeno-associated virus (rAAV) vectors allow for sustained expression of transgene products from mouse liver following a single portal vein administration. Here a rAAV vector expressing...
Integrating Adenovirus–Adeno-Associated Virus Hybrid Vectors Devoid of All Viral Genes
Lieber, André, Steinwaerder, Dirk S., Carlson, Cheryl A., Kay, Mark A.
Recently, we demonstrated that inverted repeat sequences inserted into first-generation adenovirus (Ad) vector genomes mediate precise genomic rearrangements resulting in vector genomes devoid of all...
Nakai, Hiroyuki, Yant, Stephen R., Storm, Theresa A., Fuess, Sally, Meuse, Leonard, Kay, Mark A.
Recombinant adeno-associated virus (rAAV) vectors stably transduce hepatocytes in experimental animals. Although the vector genomes are found both as extrachromosomes and as chromosomally integrated...
A Prenylation Inhibitor Prevents Production of Infectious Hepatitis Delta Virus Particles
Bordier, Bruno B., Marion, Patricia L., Ohashi, Kazuo, Kay, Mark A., Greenberg, Harry B., Casey, John L., ...
Hepatitis delta virus (HDV) causes both acute and chronic liver disease throughout the world. Effective medical therapy is lacking. Previous work has shown that the assembly of HDV virus-like...
Nakai, Hiroyuki, Thomas, Clare E., Storm, Theresa A., Fuess, Sally, Powell, Sharon, Wright, J. Fraser, ...
Recombinant adeno-associated virus (rAAV) vectors are promising vehicles for achieving stable liver transduction in vivo. However, the mechanisms of liver transduction are not fully understood, and...
Episomal Persistence of Recombinant Adenoviral Vector Genomes during the Cell Cycle In Vivo
Ehrhardt, Anja, Xu, Hui, Kay, Mark A.
Previously we showed that recombinant adenoviral helper-dependent (HD) vectors result in long-term transgene expression levels in vivo which slowly declined by 95% over a period of 1 year. In this...
In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus
Bordier, Bruno B., Ohkanda, Junko, Liu, Ping, Lee, So-Young, Salazar, F.H., Marion, Patricia L., ...
Hepatitis delta virus (HDV) can dramatically worsen liver disease in patients coinfected with hepatitis B virus (HBV). No effective medical therapy exists for HDV. The HDV envelope requires HBV...
Yant, Stephen R., Kay, Mark A.
Herein, we report that the DNA-dependent protein kinase (DNA-PK) regulates the DNA damage introduced during Sleeping Beauty (SB) element excision and reinsertion in mammalian cells. Using both...
Thomas, Clare E., Storm, Theresa A., Huang, Zan, Kay, Mark A.
Transduction of the liver with single-stranded adeno-associated virus serotype 2 (AAV2) vectors is inefficient; less than 10% of hepatocytes are permissive for stable transduction, and transgene...
Yant, Stephen R., Park, Julie, Huang, Yong, Mikkelsen, Jacob Giehm, Kay, Mark A.
The N-terminal domain of the Sleeping Beauty (SB) transposase mediates transposon DNA binding, subunit multimerization, and nuclear translocation in vertebrate cells. For this report, we studied the...
Unrestricted Hepatocyte Transduction with Adeno-Associated Virus Serotype 8 Vectors in Mice
Nakai, Hiroyuki, Fuess, Sally, Storm, Theresa A., Muramatsu, Shin-ichi, Nara, Yuko, Kay, Mark A.
Recombinant adeno-associated virus (rAAV) vectors can mediate long-term stable transduction in various target tissues. However, with rAAV serotype 2 (rAAV2) vectors, liver transduction is confined to...
High-Resolution Genome-Wide Mapping of Transposon Integration in Mammals
Yant, Stephen R., Wu, Xiaolin, Huang, Yong, Garrison, Brian, Burgess, Shawn M., Kay, Mark A.
The Sleeping Beauty (SB) transposon is an emerging tool for transgenesis, gene discovery, and therapeutic gene delivery in mammals. Here we studied 1,336 SB insertions in primary and cultured...
Large-Scale Molecular Characterization of Adeno-Associated Virus Vector Integration in Mouse Liver
Nakai, Hiroyuki, Wu, Xiaolin, Fuess, Sally, Storm, Theresa A., Munroe, David, Montini, Eugenio, ...
Recombinant adeno-associated virus (rAAV) vector holds promise for gene therapy. Despite a low frequency of chromosomal integration of vector genomes, recent studies have raised concerns about the...
Grimm, Dirk, Pandey, Kusum, Nakai, Hiroyuki, Storm, Theresa A., Kay, Mark A.
We and others have recently reported highly efficient liver gene transfer with adeno-associated virus 8 (AAV-8) pseudotypes, i.e., AAV-2 genomes packaged into AAV-8 capsids. Here we studied whether...
In vivo activity of nuclease-resistant siRNAs
LAYZER, JULIANA M., MCCAFFREY, ANTON P., TANNER, ALICE K., HUANG, ZAN, KAY, MARK A., SULLENGER, BRUCE A.
Chemical modifications have been incorporated into short interfering RNAs (siRNAs) without reducing their ability to inhibit gene expression in mammalian cells grown in vitro. In this study, we begin...
Kay, Mark A., Meuse, Leonard, Gown, Allen M., Linsley, Peter, Hollenbaugh, Diane, Aruffo, Alejandro, ...
Although recombinant adenovirus vectors offer a very efficient means by which to transfer genetic information into cells in vivo, antigen-dependent immunity limits the duration of gene expression and...
Kay, Mark A., Liu, Dexi, Hoogerbrugge, Peter M.
In recent years, there have been a number of technological breakthroughs that have allowed for clinical trials in gene therapy to be initiated. In combination with the genome initiative, the...
Correction of the retinal dystrophy phenotype of the RCS rat by viral gene transfer of Mertk
Vollrath, Douglas, Feng, Wei, Duncan, Jacque L., Yasumura, Douglas, D'Cruz, Patricia M., Chappelow, Aimee, ...
The Royal College of Surgeons (RCS) rat is a widely studied animal model of retinal degeneration in which the inability of the retinal pigment epithelium (RPE) to phagocytize shed photoreceptor outer...
Wilson, Christopher B., Embree, Lisa J., Schowalter, David, Albert, Richard, Aruffo, Alejandro, Hollenbaugh, Diane, ...
Recombinant adenovirus vectors have been used to transfer genes to the lungs in animal models, but the extent and duration of primary transgene expression and the ability to achieve expression after...
Lieber, André, He, Chen-Yi, Meuse, Leonard, Himeda, Charis, Wilson, Christopher, Kay, Mark A.
NF-κB is a key regulator of the innate antiviral immune response, due in part to its transcriptional activation of cytokines and adhesion molecules, which, in turn, function in chemotaxis and...
Lieber, André, Kay, Mark A., Li, Zong-Yi
Moloney murine leukemia virus (MoMLV)-derived vectors require cell division for efficient transduction, which may be related to an inability of the viral DNA-protein complex to cross the nuclear...
Miao, Carol H., Nakai, Hiroyuki, Thompson, Arthur R., Storm, Theresa A., Chiu, Winnie, Snyder, Richard O., ...
Recombinant adeno-associated virus vectors (rAAV) show promise in preclinical trials for the treatment of genetic diseases including hemophilia. Liver-directed gene transfer results in a slow rise in...
Nakai, Hiroyuki, Storm, Theresa A., Kay, Mark A.
Recombinant adeno-associated virus (rAAV) vectors stably transduce hepatocytes in experimental animals. Following portal-vein administration of rAAV vectors in vivo, single-stranded (ss) rAAV genomes...
Schowalter, David B., Himeda, Charis L., Winther, Brian L., Wilson, Christopher B., Kay, Mark A.
This study explores the genetic and immunologic factors involved in the differences in duration of transgene expression following in vivo transduction with recombinant adenoviruses. Different strains...
Isolation of Recombinant Adeno-Associated Virus Vector-Cellular DNA Junctions from Mouse Liver
Nakai, Hiroyuki, Iwaki, Yuichi, Kay, Mark A., Couto, Linda B.
Recombinant adeno-associated virus (rAAV) vectors allow for sustained expression of transgene products from mouse liver following a single portal vein administration. Here a rAAV vector expressing...
Integrating Adenovirus–Adeno-Associated Virus Hybrid Vectors Devoid of All Viral Genes
Lieber, André, Steinwaerder, Dirk S., Carlson, Cheryl A., Kay, Mark A.
Recently, we demonstrated that inverted repeat sequences inserted into first-generation adenovirus (Ad) vector genomes mediate precise genomic rearrangements resulting in vector genomes devoid of all...
Nakai, Hiroyuki, Yant, Stephen R., Storm, Theresa A., Fuess, Sally, Meuse, Leonard, Kay, Mark A.
Recombinant adeno-associated virus (rAAV) vectors stably transduce hepatocytes in experimental animals. Although the vector genomes are found both as extrachromosomes and as chromosomally integrated...
A Prenylation Inhibitor Prevents Production of Infectious Hepatitis Delta Virus Particles
Bordier, Bruno B., Marion, Patricia L., Ohashi, Kazuo, Kay, Mark A., Greenberg, Harry B., Casey, John L., ...
Hepatitis delta virus (HDV) causes both acute and chronic liver disease throughout the world. Effective medical therapy is lacking. Previous work has shown that the assembly of HDV virus-like...
Nakai, Hiroyuki, Thomas, Clare E., Storm, Theresa A., Fuess, Sally, Powell, Sharon, Wright, J. Fraser, ...
Recombinant adeno-associated virus (rAAV) vectors are promising vehicles for achieving stable liver transduction in vivo. However, the mechanisms of liver transduction are not fully understood, and...
Episomal Persistence of Recombinant Adenoviral Vector Genomes during the Cell Cycle In Vivo
Ehrhardt, Anja, Xu, Hui, Kay, Mark A.
Previously we showed that recombinant adenoviral helper-dependent (HD) vectors result in long-term transgene expression levels in vivo which slowly declined by 95% over a period of 1 year. In this...
In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus
Bordier, Bruno B., Ohkanda, Junko, Liu, Ping, Lee, So-Young, Salazar, F.H., Marion, Patricia L., ...
Hepatitis delta virus (HDV) can dramatically worsen liver disease in patients coinfected with hepatitis B virus (HBV). No effective medical therapy exists for HDV. The HDV envelope requires HBV...
Yant, Stephen R., Kay, Mark A.
Herein, we report that the DNA-dependent protein kinase (DNA-PK) regulates the DNA damage introduced during Sleeping Beauty (SB) element excision and reinsertion in mammalian cells. Using both...
Thomas, Clare E., Storm, Theresa A., Huang, Zan, Kay, Mark A.
Transduction of the liver with single-stranded adeno-associated virus serotype 2 (AAV2) vectors is inefficient; less than 10% of hepatocytes are permissive for stable transduction, and transgene...
Yant, Stephen R., Park, Julie, Huang, Yong, Mikkelsen, Jacob Giehm, Kay, Mark A.
The N-terminal domain of the Sleeping Beauty (SB) transposase mediates transposon DNA binding, subunit multimerization, and nuclear translocation in vertebrate cells. For this report, we studied the...
Unrestricted Hepatocyte Transduction with Adeno-Associated Virus Serotype 8 Vectors in Mice
Nakai, Hiroyuki, Fuess, Sally, Storm, Theresa A., Muramatsu, Shin-ichi, Nara, Yuko, Kay, Mark A.
Recombinant adeno-associated virus (rAAV) vectors can mediate long-term stable transduction in various target tissues. However, with rAAV serotype 2 (rAAV2) vectors, liver transduction is confined to...
High-Resolution Genome-Wide Mapping of Transposon Integration in Mammals
Yant, Stephen R., Wu, Xiaolin, Huang, Yong, Garrison, Brian, Burgess, Shawn M., Kay, Mark A.
The Sleeping Beauty (SB) transposon is an emerging tool for transgenesis, gene discovery, and therapeutic gene delivery in mammals. Here we studied 1,336 SB insertions in primary and cultured...
Large-Scale Molecular Characterization of Adeno-Associated Virus Vector Integration in Mouse Liver
Nakai, Hiroyuki, Wu, Xiaolin, Fuess, Sally, Storm, Theresa A., Munroe, David, Montini, Eugenio, ...
Recombinant adeno-associated virus (rAAV) vector holds promise for gene therapy. Despite a low frequency of chromosomal integration of vector genomes, recent studies have raised concerns about the...
Grimm, Dirk, Pandey, Kusum, Nakai, Hiroyuki, Storm, Theresa A., Kay, Mark A.
We and others have recently reported highly efficient liver gene transfer with adeno-associated virus 8 (AAV-8) pseudotypes, i.e., AAV-2 genomes packaged into AAV-8 capsids. Here we studied whether...
In vivo activity of nuclease-resistant siRNAs
LAYZER, JULIANA M., MCCAFFREY, ANTON P., TANNER, ALICE K., HUANG, ZAN, KAY, MARK A., SULLENGER, BRUCE A.
Chemical modifications have been incorporated into short interfering RNAs (siRNAs) without reducing their ability to inhibit gene expression in mammalian cells grown in vitro. In this study, we begin...
Akache, Bassel, Grimm, Dirk, Pandey, Kusum, Yant, Stephen R., Xu, Hui, Kay, Mark A.
Adeno-associated virus serotype 8 (AAV8) is currently emerging as a powerful gene transfer vector, owing to its capability to efficiently transduce many different tissues in vivo. While this is...
Site-directed transposon integration in human cells
Yant, Stephen R., Huang, Yong, Akache, Bassel, Kay, Mark A.
The Sleeping Beauty (SB) transposon is a promising gene transfer vector that integrates nonspecifically into host cell genomes. Herein, we attempt to direct transposon integration into predetermined...
Host factors that impact the biodistribution and persistence of multipotent adult progenitor cells
Tolar, Jakub, O'Shaughnessy, Matthew J., Panoskaltsis-Mortari, Angela, McElmurry, Ron T., Bell, Scott, Riddle, Megan, ...
Multipotent adult progenitor cells (MAPCs) are marrow-derived pluripotent stem cells with a broad differentiation potential. We sought to identify factors that affect adoptively transferred MAPCs. In...
Therapeutic application of RNAi: is mRNA targeting finally ready for prime time?
With unprecedented speed, RNA interference (RNAi) has advanced from its basic discovery in lower organisms to becoming a powerful genetic tool and perhaps our single most promising biotherapeutic for...
Inagaki, Katsuya, Lewis, Susanna M., Wu, Xiaolin, Ma, Congrong, Munroe, David J., Fuess, Sally, ...
Our previous study has shown that recombinant adeno-associated virus (rAAV) vector integrates preferentially in genes, near transcription start sites and CpG islands in mouse liver (H. Nakai, X. Wu,...
The Role of DNA-PKcs and Artemis in Opening Viral DNA Hairpin Termini in Various Tissues in Mice▿
Inagaki, Katsuya, Ma, Congrong, Storm, Theresa A., Kay, Mark A., Nakai, Hiroyuki
A subset of cellular DNA hairpins at double-strand breaks is processed by DNA-dependent protein kinase catalytic subunit (DNA-PKcs)- and Artemis-associated endonuclease. DNA hairpin termini of...
Distinct pathways of genomic progression to benign and malignant tumors of the liver
Tward, Aaron D., Jones, Kirk D., Yant, Stephen, Cheung, Siu Tim, Fan, Sheung Tat, Chen, Xin, ...
We used several of the genetic lesions commonly associated with human liver tumors to reconstruct genetic progression to hepatocellular carcinoma and adenoma in mouse models. We initiated...
Postintegrative Gene Silencing within the Sleeping Beauty Transposition System▿
Garrison, Brian S., Yant, Stephen R., Mikkelsen, Jacob Giehm, Kay, Mark A.
The Sleeping Beauty (SB) transposon represents an important vehicle for in vivo gene delivery because it can efficiently and stably integrate into mammalian genomes. In this report, we examined...
Grimm, Dirk, Lee, Joyce S., Wang, Lora, Desai, Tushar, Akache, Bassel, Storm, Theresa A., ...
Adeno-associated virus (AAV) serotypes differ broadly in transduction efficacies and tissue tropisms and thus hold enormous potential as vectors for human gene therapy. In reality, however, their use...
Doege, Holger, Grimm, Dirk, Falcon, Alaric, Tsang, Bernice, Storm, Theresa A., Xu, Hui, ...
Non-alcoholic fatty liver disease is a serious health problem linked to obesity and type 2 diabetes. To investigate the biological outcome and therapeutic potential of hepatic fatty acid uptake...