Eslamboli, Andisheh, Romero-Ramos, Marina, Burger, Corinna, Bjorklund, Tomas, Muzyczka, Nicholas, Mandel, Ronald J, ...
Abstract is not available
Eslamboli, Andisheh, Romero-Ramos, Marina, Burger, Corinna, Bjorklund, Tomas, Muzyczka, Nicholas, Mandel, Ronald J., ...
Overexpression of human α-synuclein (α-syn) using recombinant adeno-associated viral (rAAV) vectors provides a novel tool to study neurodegenerative processes seen in Parkinson's disease and other...
Eslamboli, Andisheh, Romero-Ramos, Marina, Burger, Corinna, Bjorklund, Tomas, Muzyczka, Nicholas, Mandel, Ronald J., ...
Overexpression of human α-synuclein (α-syn) using recombinant adeno-associated viral (rAAV) vectors provides a novel tool to study neurodegenerative processes seen in Parkinson's disease and other...
Carlsson, Thomas, Winkler, Christian, Burger, Corinna, Muzyczka, Nicholas, Mandel, Ronald J, Cenci, Angela, ...
Abstract is not available
Carlsson, Thomas, Winkler, Christian, Burger, Corinna, Muzyczka, Nicholas, Mandel, Ronald J., Cenci, Angela, ...
Dyskinesias are a major complication of long-term l-3,4-dihydroxyphenylalanine (l-DOPA) treatment in Parkinson's disease, and are believed to result from the intermittent and pulsatile supply of...
Carlsson, Thomas, Winkler, Christian, Burger, Corinna, Muzyczka, Nicholas, Mandel, Ronald J., Cenci, Angela, ...
Summary Dyskinesias are a major complication of long-term L-3,4-dihydroxyphenylalanine (L-DOPA) treatment in Parkinson's disease, and are believed to result from the intermittent and pulsatile supply...
Carlsson, Thomas, Winkler, Christian, Burger, Corinna, Muzyczka, Nicholas, Mandel, Ronald J., Cenci, Angela, ...
Summary Dyskinesias are a major complication of long-term L-3,4-dihydroxyphenylalanine (L-DOPA) treatment in Parkinson's disease, and are believed to result from the intermittent and pulsatile supply...
Kirik, Deniz, Annett, Lucy E., Burger, Corinna, Muzyczka, Nicholas, Mandel, Ronald J., Bjorklund, Anders
Abstract is not available
Andsberg, Gunnar, Kokaia, Zaal, Klein, Ronald L, Muzyczka, Nicholas, Lindvall, Olle, Mandel, Ronald J
Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were continuously delivered to the striatum at biologically active levels via recombinant adeno-associated viral (rAAV) gene...
Kirik, Deniz, Rosenblad, Carl, Burger, Corinna, Lundberg, Cecilia, Johansen, Teit E, Muzyczka, Nicholas, ...
Recombinant adeno-associated viral vectors display efficient tropism for transduction of the dopamine neurons of the substantia nigra. Taking advantage of this unique property of recombinant...
Kirik, Deniz, Georgievska, Biljana, Burger, Corinna, Winkler, Christian, Muzyczka, Nicholas, Mandel, Ronald J, ...
Intrastriatal delivery of the tyrosine hydroxylase gene by viral vectors is being explored as a tool for local delivery of L-dopa in animals with lesions of the nigrostriatal pathway. The functional...
Larsson, Elin, Mandel, Ronald J, Klein, Ronald L, Muzyczka, Nicholas, Lindvall, Olle, Kokaia, Zaal
Abstract is not available
Cre-mediated recombination in the pituitary gland (2000)
Cushman, Lisa J., Burrows, Heather L., Seasholtz, Audrey F., Lewandoski, Mark, Muzyczka, Nicholas, Camper, Sally A.
Summary: Organ-specific expression of a cre recombinase transgene allows for the analysis of gene function in a particular tissue or cell type. Using a 4.6 kb promoter from the mouse glycoprotein...
Sergei Zolotukhin, Mark Potter, William W. Hauswirth, John Guy, Nicholas Muzyczka
We constructed gfp h, a synthetic version of the jellyfish Aequorea victoria green fluorescent protein (gfp) cDNA that is adapted for high-level expression in mammalian cells, especially those of...
Efficient photoreceptor-targeted gene expression in vivo by recombinant adeno-associated virus
Flannery, John G., Zolotukhin, Sergei, Vaquero, M. Isabel, LaVail, Matthew M., Muzyczka, Nicholas, Hauswirth, William W.
We describe a general approach for achieving efficient and cell type-specific expression of exogenous genes in photoreceptor cells of the mammalian retina. Recombinant adeno-associated virus (rAAV)...
Song, Sihong, Morgan, Michael, Ellis, Tamir, Poirier, Amy, Chesnut, Kye, Wang, Jianming, ...
Recombinant adeno-associated virus (AAV) vectors have been used to transduce murine skeletal muscle as a platform for secretion of therapeutic proteins. The utility of this approach for treating...
Wu, Pei, Xiao, Wu, Conlon, Thomas, Hughes, Jeffrey, Agbandje-McKenna, Mavis, Ferkol, Thomas, ...
Adeno-associated virus type 2 (AAV2) has proven to be a valuable vector for gene therapy. Characterization of the functional domains of the AAV capsid proteins can facilitate our understanding of...
Biochemical Characterization of Adeno-Associated Virus Rep68 DNA Helicase and ATPase Activities
Zhou, Xiaohuai, Zolotukhin, Irene, Im, Dong-Soo, Muzyczka, Nicholas
The adeno-associated virus (AAV) nonstructural proteins Rep68 and Rep78 are site-specific DNA binding proteins, ATP-dependent site-specific endonucleases, helicases, and ATPases. These biochemical...
Ni, Tie-Hua, McDonald, William F., Zolotukhin, Irene, Melendy, Thomas, Waga, Shou, Stillman, Bruce, ...
We previously reported the development of an in vitro adeno-associated virus (AAV) DNA replication system. The system required one of the p5 Rep proteins encoded by AAV (either Rep78 or Rep68) and a...
In Vitro Packaging of Adeno-Associated Virus DNA
Zhou, Xiaohuai, Muzyczka, Nicholas
We have developed an in vitro procedure for packaging of recombinant adeno-associated virus (AAV). By using AAV replicative-form DNA as the substrate, it is possible to synthesize an infectious AAV...
Gavin, Denise K., Young, Samuel M., Xiao, Weidong, Temple, Brenda, Abernathy, Corinne R., Pereira, Daniel J., ...
Mechanism of Rep-Mediated Adeno-Associated Virus Origin Nicking
Brister, J. Rodney, Muzyczka, Nicholas
The single-stranded adeno-associated virus type 2 (AAV) genome is flanked by terminal repeats (TRs) that fold back on themselves to form hairpinned structures. During AAV DNA replication, the TRs are...
Brister, J. Rodney, Muzyczka, Nicholas
The single-stranded adeno-associated virus (AAV) genome is flanked by terminal hairpinned origins of DNA replication (terminal repeats [TRs]) that are nicked at the terminal resolution site (trs) by...
Gavin, Denise K., Young, Samuel M., Xiao, Weidong, Temple, Brenda, Abernathy, Corinne R., Pereira, Daniel J., ...
The adeno-associated virus type 2 (AAV) replication (Rep) proteins Rep78 and 68 (Rep78/68) exhibit a number of biochemical activities required for AAV replication, including specific binding to a...
Kirik, Deniz, Georgievska, Biljana, Burger, Corinna, Winkler, Christian, Muzyczka, Nicholas, Mandel, Ronald J., ...
Intrastriatal delivery of the tyrosine hydroxylase gene by viral vectors is being explored as a tool for local delivery of l-dopa in animals with lesions of the nigrostriatal pathway. The functional...
Adenovirus-Facilitated Nuclear Translocation of Adeno-Associated Virus Type 2
Xiao, Wu, Warrington, Kenneth H., Hearing, Patrick, Hughes, Jeffrey, Muzyczka, Nicholas
We examined cytoplasmic trafficking and nuclear translocation of adeno-associated virus type 2 (AAV) by using Alexa Fluor 488-conjugated wild-type AAV, A20 monoclonal antibody immunocytochemistry,...
Kirik, Deniz, Annett, Lucy E., Burger, Corinna, Muzyczka, Nicholas, Mandel, Ronald J., Björklund, Anders
We used a high-titer recombinant adeno-associated virus (rAAV) vector to express WT or mutant human α-synuclein in the substantia nigra of adult marmosets. The α-synuclein protein was expressed in...
Opie, Shaun R., Agbandje-McKenna, Mavis, Zolotukhin, Sergei, Muzyczka, Nicholas
The adeno-associated virus type 2 (AAV2) uses heparan sulfate proteoglycan (HSPG) as its primary cellular receptor. In order to identify amino acids within the capsid of AAV2 that contribute to HSPG...
Peden, Carmen S., Burger, Corinna, Muzyczka, Nicholas, Mandel, Ronald J.
Epidemiological studies report that 80% of the population maintains antibodies (Ab) to wild-type (wt) adeno-associated virus type 2 (AAV2), with 30% expressing neutralizing Ab (NAb). The blood-brain...
Warrington, Kenneth H., Gorbatyuk, Oleg S., Harrison, Jeffrey K., Opie, Shaun R., Zolotukhin, Sergei, Muzyczka, Nicholas
Direct insertion of amino acid sequences into the adeno-associated virus type 2 (AAV) capsid open reading frame (cap ORF) is one strategy currently being developed for retargeting this prototypical...
Structure of Adeno-Associated Virus Type 4
Padron, Eric, Bowman, Valorie, Kaludov, Nikola, Govindasamy, Lakshmanan, Levy, Hazel, Nick, Phillip, ...
Adeno-associated virus (AAV) is a member of the Parvoviridae, belonging to the Dependovirus genus. Currently, several distinct isolates of AAV are in development for use in human gene therapy...
Successful Production of Pseudotyped rAAV Vectors Using a Modified Baculovirus Expression System
Kohlbrenner, Erik, Aslanidi, George, Nash, Kevin, Shklyaev, Stanislav, Campbell-Thompson, Martha, Byrne, Barry J., ...
Scalable production of rAAV vectors remains a major obstacle to the clinical application of this prototypical gene therapy vector. A recently developed baculovirus-based production protocol (M. Urabe...
Lackner, Daniel F., Muzyczka, Nicholas
During adeno-associated virus (AAV) type 2 productive infections, the p19 promoter of AAV is activated by the AAV Rep78 and Rep68 proteins. Rep-induced activation of p19 depends on the presence of...
Efficient photoreceptor-targeted gene expression in vivo by recombinant adeno-associated virus
Flannery, John G., Zolotukhin, Sergei, Vaquero, M. Isabel, LaVail, Matthew M., Muzyczka, Nicholas, Hauswirth, William W.
We describe a general approach for achieving efficient and cell type-specific expression of exogenous genes in photoreceptor cells of the mammalian retina. Recombinant adeno-associated virus (rAAV)...
Song, Sihong, Morgan, Michael, Ellis, Tamir, Poirier, Amy, Chesnut, Kye, Wang, Jianming, ...
Recombinant adeno-associated virus (AAV) vectors have been used to transduce murine skeletal muscle as a platform for secretion of therapeutic proteins. The utility of this approach for treating...
Wu, Pei, Xiao, Wu, Conlon, Thomas, Hughes, Jeffrey, Agbandje-McKenna, Mavis, Ferkol, Thomas, ...
Adeno-associated virus type 2 (AAV2) has proven to be a valuable vector for gene therapy. Characterization of the functional domains of the AAV capsid proteins can facilitate our understanding of...
Biochemical Characterization of Adeno-Associated Virus Rep68 DNA Helicase and ATPase Activities
Zhou, Xiaohuai, Zolotukhin, Irene, Im, Dong-Soo, Muzyczka, Nicholas
The adeno-associated virus (AAV) nonstructural proteins Rep68 and Rep78 are site-specific DNA binding proteins, ATP-dependent site-specific endonucleases, helicases, and ATPases. These biochemical...
Ni, Tie-Hua, McDonald, William F., Zolotukhin, Irene, Melendy, Thomas, Waga, Shou, Stillman, Bruce, ...
We previously reported the development of an in vitro adeno-associated virus (AAV) DNA replication system. The system required one of the p5 Rep proteins encoded by AAV (either Rep78 or Rep68) and a...
In Vitro Packaging of Adeno-Associated Virus DNA
Zhou, Xiaohuai, Muzyczka, Nicholas
We have developed an in vitro procedure for packaging of recombinant adeno-associated virus (AAV). By using AAV replicative-form DNA as the substrate, it is possible to synthesize an infectious AAV...
Gavin, Denise K., Young, Samuel M., Xiao, Weidong, Temple, Brenda, Abernathy, Corinne R., Pereira, Daniel J., ...
Mechanism of Rep-Mediated Adeno-Associated Virus Origin Nicking
Brister, J. Rodney, Muzyczka, Nicholas
The single-stranded adeno-associated virus type 2 (AAV) genome is flanked by terminal repeats (TRs) that fold back on themselves to form hairpinned structures. During AAV DNA replication, the TRs are...
Brister, J. Rodney, Muzyczka, Nicholas
The single-stranded adeno-associated virus (AAV) genome is flanked by terminal hairpinned origins of DNA replication (terminal repeats [TRs]) that are nicked at the terminal resolution site (trs) by...
Gavin, Denise K., Young, Samuel M., Xiao, Weidong, Temple, Brenda, Abernathy, Corinne R., Pereira, Daniel J., ...
The adeno-associated virus type 2 (AAV) replication (Rep) proteins Rep78 and 68 (Rep78/68) exhibit a number of biochemical activities required for AAV replication, including specific binding to a...
Kirik, Deniz, Georgievska, Biljana, Burger, Corinna, Winkler, Christian, Muzyczka, Nicholas, Mandel, Ronald J., ...
Intrastriatal delivery of the tyrosine hydroxylase gene by viral vectors is being explored as a tool for local delivery of l-dopa in animals with lesions of the nigrostriatal pathway. The functional...
Adenovirus-Facilitated Nuclear Translocation of Adeno-Associated Virus Type 2
Xiao, Wu, Warrington, Kenneth H., Hearing, Patrick, Hughes, Jeffrey, Muzyczka, Nicholas
We examined cytoplasmic trafficking and nuclear translocation of adeno-associated virus type 2 (AAV) by using Alexa Fluor 488-conjugated wild-type AAV, A20 monoclonal antibody immunocytochemistry,...
Kirik, Deniz, Annett, Lucy E., Burger, Corinna, Muzyczka, Nicholas, Mandel, Ronald J., Björklund, Anders
We used a high-titer recombinant adeno-associated virus (rAAV) vector to express WT or mutant human α-synuclein in the substantia nigra of adult marmosets. The α-synuclein protein was expressed in...
Lackner, Daniel F., Muzyczka, Nicholas
During adeno-associated virus (AAV) type 2 productive infections, the p19 promoter of AAV is activated by the AAV Rep78 and Rep68 proteins. Rep-induced activation of p19 depends on the presence of...
Opie, Shaun R., Agbandje-McKenna, Mavis, Zolotukhin, Sergei, Muzyczka, Nicholas
The adeno-associated virus type 2 (AAV2) uses heparan sulfate proteoglycan (HSPG) as its primary cellular receptor. In order to identify amino acids within the capsid of AAV2 that contribute to HSPG...
Peden, Carmen S., Burger, Corinna, Muzyczka, Nicholas, Mandel, Ronald J.
Epidemiological studies report that 80% of the population maintains antibodies (Ab) to wild-type (wt) adeno-associated virus type 2 (AAV2), with 30% expressing neutralizing Ab (NAb). The blood-brain...
Warrington, Kenneth H., Gorbatyuk, Oleg S., Harrison, Jeffrey K., Opie, Shaun R., Zolotukhin, Sergei, Muzyczka, Nicholas
Direct insertion of amino acid sequences into the adeno-associated virus type 2 (AAV) capsid open reading frame (cap ORF) is one strategy currently being developed for retargeting this prototypical...
Structure of Adeno-Associated Virus Type 4
Padron, Eric, Bowman, Valorie, Kaludov, Nikola, Govindasamy, Lakshmanan, Levy, Hazel, Nick, Phillip, ...
Adeno-associated virus (AAV) is a member of the Parvoviridae, belonging to the Dependovirus genus. Currently, several distinct isolates of AAV are in development for use in human gene therapy...
Structurally Mapping the Diverse Phenotype of Adeno-Associated Virus Serotype 4▿
Govindasamy, Lakshmanan, Padron, Eric, McKenna, Robert, Muzyczka, Nicholas, Kaludov, Nikola, Chiorini, John A., ...
The adeno-associated viruses (AAVs) can package and deliver foreign DNA into cells for corrective gene delivery applications. The AAV serotypes have distinct cell binding, transduction, and antigenic...
Lane, Michael Douglas, Nam, Hyun-Joo, Padron, Eric, Gurda-Whitaker, Brittney, Kohlbrenner, Eric, Aslanidi, George, ...
The production, purification, crystallization and preliminary X-ray crystallographic analysis of adeno-associated virus serotype 8 is reported.
Purification of Host Cell Enzymes Involved in Adeno-Associated Virus DNA Replication▿
Nash, Kevin, Chen, Weijun, McDonald, William F., Zhou, Xiaohuai, Muzyczka, Nicholas
Adeno-associated virus (AAV) replicates its DNA by a modified rolling-circle mechanism that exclusively uses leading strand displacement synthesis. To identify the enzymes directly involved in AAV...
DiMattia, Michael, Govindasamy, Lakshmanan, Levy, Hazel C., Gurda-Whitaker, Brittney, Kalina, Amy, Kohlbrenner, Erik, ...
The production, purification, crystallization and preliminary crystallographic analysis of empty adeno-associated virus serotype 5 capsids are reported.
Structure of Adeno-Associated Virus Serotype 8, a Gene Therapy Vector▿
Nam, Hyun-Joo, Lane, Michael Douglas, Padron, Eric, Gurda, Brittney, McKenna, Robert, Kohlbrenner, Erik, ...
Adeno-associated viruses (AAVs) are being developed as gene therapy vectors, and their efficacy could be improved by a detailed understanding of their viral capsid structures. AAV serotype 8 (AAV8)...
Nash, Kevin, Chen, Weijun, Muzyczka, Nicholas
Adeno-associated virus (AAV) replicates its DNA exclusively by a leading-strand DNA replication mechanism and requires coinfection with a helper virus, such as adenovirus, to achieve a productive...
Gorbatyuk, Oleg S., Li, Shoudong, Sullivan, Layla F., Chen, Weijun, Kondrikova, Galina, Manfredsson, Fredric P., ...
Studies have shown that α-synuclein (α-syn) deposited in Lewy bodies in brain tissue from patients with Parkinson disease (PD) is extensively phosphorylated at Ser-129. We used recombinant...
Miller, Edward B., Gurda-Whitaker, Brittney, Govindasamy, Lakshmanan, McKenna, Robert, Zolotukhin, Sergei, Muzyczka, Nicholas, ...
Crystals of baculovirus-expressed adeno-associated virus serotype 1 (AAV1) capsids have been grown in the rhombohedral space group R32 (unit-cell parameters a = 254.7 Å, α = 62.3°) and shown to...
Zhong, Li, Li, Baozheng, Mah, Cathryn S., Govindasamy, Lakshmanan, Agbandje-McKenna, Mavis, Cooper, Mario, ...
Recombinant adeno-associated virus 2 (AAV2) vectors are in use in several Phase I/II clinical trials, but relatively large vector doses are needed to achieve therapeutic benefits. Large vector doses...
Identification of Cellular Proteins That Interact with the Adeno-Associated Virus Rep Protein▿
Nash, Kevin, Chen, Weijun, Salganik, Max, Muzyczka, Nicholas
Adeno-associated virus (AAV) codes for four related nonstructural Rep proteins. AAV both replicates and assembles in the nucleus and requires coinfection with a helper virus, either adenovirus (Ad)...