Efficient expression of protein coding genes from the murine U1 small nuclear RNA promoters.
Bartlett, J S, Sethna, M, Ramamurthy, L, Gowen, S A, Samulski, R J, Marzluff, W F
Few promoters are active at high levels in all cells. Of these, the majority encode structural RNAs transcribed by RNA polymerases I or III and are not accessible for the expression of proteins. An...
Miller, J L, Donahue, R E, Sellers, S E, Samulski, R J, Young, N S, Nienhuis, A W
Effective gene therapy for the severe hemoglobin (Hb) disorders, sickle-cell anemia and thalassemia, will require an efficient method to transfer, integrate, and express a globin gene in primary...
Walsh, C E, Liu, J M, Xiao, X, Young, N S, Nienhuis, A W, Samulski, R J
Gene therapy of severe hemoglobinopathies will require high-level expression of a transferred globin gene in erythroid cells. Distant regulatory elements flanking the beta-globin gene cluster, the...
Site-specific integration by adeno-associated virus.
Kotin, R M, Siniscalco, M, Samulski, R J, Zhu, X D, Hunter, L, Laughlin, C A, ...
Cellular sequences flanking integrated copies of the adeno-associated virus (AAV) genome were isolated from a latently infected clonal human cell line and used to probe genomic blots derived from an...
Teramoto, S., Bartlett, J. S., McCarty, D., Xiao, X., Samulski, R. J., Boucher, R. C.
Adeno-associated virus (AAV) vectors appear promising for use in gene therapy in cystic fibrosis (CF) patients, yet many features of AAV-mediated gene transfer to airway epithelial cells are not well...
Ferrari, F K, Samulski, T, Shenk, T, Samulski, R J
The ability of recombinant adeno-associated virus (AAV) to transduce cells with a marker gene in vitro was found to be substantially increased by the presence of adenovirus. Transfection experiments...
Muscle-directed gene transfer is being considered for the treatment of several metabolic diseases, including hemophilia and Duchene's muscular dystrophy. Previous efforts to target this tissue for...
Xiao, X, Xiao, W, Li, J, Samulski, R J
Adeno-associated virus (AAV) replication is dependent on two copies of a 145-bp inverted terminal repeat (ITR) that flank the AAV genome. This is the primary cis-acting element required for...
Role for highly regulated rep gene expression in adeno-associated virus vector production.
Recent success achieving long-term in vivo gene transfer without a significant immune response by using adeno-associated virus (AAV) vectors (X. Xiao, J. Li, and R. J. Samulski, J. Virol....
Yang, C C, Xiao, X, Zhu, X, Ansardi, D C, Epstein, N D, Frey, M R, ...
The human parvovirus adeno-associated virus (AAV) is unique in its ability to target viral integration to a specific site on chromosome 19 (ch-19). Recombinant AAV (rAAV) vectors retain the ability...
Snyder, R O, Im, D S, Ni, T, Xiao, X, Samulski, R J, Muzyczka, N
We previously demonstrated that the adeno-associated virus (AAV) Rep68 and Rep78 proteins are able to nick the AAV origin of DNA replication at the terminal resolution site (trs) in an ATP-dependent...
Colocalization of adeno-associated virus Rep and capsid proteins in the nuclei of infected cells.
The mechanism of adeno-associated virus (AAV) DNA replication was characterized both genetically and biochemically. In this study, we used monoclonal and polyclonal antibodies to examine the AAV p5...
Adenovirus provides helper functions that facilitate replication of adeno-associated virus (AAV). Both the adenovirus E1B 55-Mr and E4 34-Mr polypeptides are required for efficient and timely...
Samulski, R J, Chang, L S, Shenk, T
A method is described for the production of recombinant adeno-associated virus (AAV) stocks that contain no detectable wild-type helper AAV. The recombinant viruses contained only the terminal 191...
Hearing, P, Samulski, R J, Wishart, W L, Shenk, T
Adenovirus type 5 deletion mutants that lack portions of their cis-acting DNA encapsidation signal synthesized nearly normal levels of viral DNA and late polypeptides but failed to efficiently...
Samulski, R J, Chang, L S, Shenk, T
A recombinant plasmid carrying an infectious adeno-associated viral genome was constructed that differs in several key respects from previously described recombinants. First, the vector is pEMBL8(+),...
Walsh, C E, Nienhuis, A W, Samulski, R J, Brown, M G, Miller, J L, Young, N S, ...
Fanconi anemia (FA) is a recessive inherited disease characterized by defective DNA repair. FA cells are hypersensitive to DNA cross-linking agents that cause chromosomal instability and cell death....
Srivastava, C H, Samulski, R J, Lu, L, Larsen, S H, Srivastava, A
To facilitate genetic analysis of the human pathogenic parvovirus B19, we constructed a hybrid B19 viral genome in which the defective B19 inverted terminal repeats were replaced with the full-length...
Samulski, R J, Berns, K I, Tan, M, Muzyczka, N
We have cloned intact duplex adeno-associated virus (AAV) DNA into the bacterial plasmid pBR322. The AAV genome could be rescued from the recombinant plasmid by transfection of the plasmid DNA into...
Targeted integration of adeno-associated virus (AAV) into human chromosome 19.
Samulski, R J, Zhu, X, Xiao, X, Brook, J D, Housman, D E, Epstein, N, ...
A key feature in adeno-associated virus (AAV) replication is efficient integration of the viral genome into host cell DNA to establish latency when helper virus is absent. The steps involved in this...
Xu, Dong, McCarty, Doug, Fernandes, Alda, Fisher, Michael, Samulski, R. J., Juliano, R. L.
Small interfering RNAs (siRNAs) are potentially powerful tools for therapeutic gene regulation. DNA cassettes encoding RNA polymerase III promoter-driven hairpin siRNAs allow long-term expression of...
Efficient expression of protein coding genes from the murine U1 small nuclear RNA promoters.
Bartlett, J S, Sethna, M, Ramamurthy, L, Gowen, S A, Samulski, R J, Marzluff, W F
Few promoters are active at high levels in all cells. Of these, the majority encode structural RNAs transcribed by RNA polymerases I or III and are not accessible for the expression of proteins. An...
Miller, J L, Donahue, R E, Sellers, S E, Samulski, R J, Young, N S, Nienhuis, A W
Effective gene therapy for the severe hemoglobin (Hb) disorders, sickle-cell anemia and thalassemia, will require an efficient method to transfer, integrate, and express a globin gene in primary...
Walsh, C E, Liu, J M, Xiao, X, Young, N S, Nienhuis, A W, Samulski, R J
Gene therapy of severe hemoglobinopathies will require high-level expression of a transferred globin gene in erythroid cells. Distant regulatory elements flanking the beta-globin gene cluster, the...
Site-specific integration by adeno-associated virus.
Kotin, R M, Siniscalco, M, Samulski, R J, Zhu, X D, Hunter, L, Laughlin, C A, ...
Cellular sequences flanking integrated copies of the adeno-associated virus (AAV) genome were isolated from a latently infected clonal human cell line and used to probe genomic blots derived from an...
Teramoto, S., Bartlett, J. S., McCarty, D., Xiao, X., Samulski, R. J., Boucher, R. C.
Adeno-associated virus (AAV) vectors appear promising for use in gene therapy in cystic fibrosis (CF) patients, yet many features of AAV-mediated gene transfer to airway epithelial cells are not well...
Ferrari, F K, Samulski, T, Shenk, T, Samulski, R J
The ability of recombinant adeno-associated virus (AAV) to transduce cells with a marker gene in vitro was found to be substantially increased by the presence of adenovirus. Transfection experiments...
Muscle-directed gene transfer is being considered for the treatment of several metabolic diseases, including hemophilia and Duchene's muscular dystrophy. Previous efforts to target this tissue for...
Xiao, X, Xiao, W, Li, J, Samulski, R J
Adeno-associated virus (AAV) replication is dependent on two copies of a 145-bp inverted terminal repeat (ITR) that flank the AAV genome. This is the primary cis-acting element required for...
Role for highly regulated rep gene expression in adeno-associated virus vector production.
Recent success achieving long-term in vivo gene transfer without a significant immune response by using adeno-associated virus (AAV) vectors (X. Xiao, J. Li, and R. J. Samulski, J. Virol....
Yang, C C, Xiao, X, Zhu, X, Ansardi, D C, Epstein, N D, Frey, M R, ...
The human parvovirus adeno-associated virus (AAV) is unique in its ability to target viral integration to a specific site on chromosome 19 (ch-19). Recombinant AAV (rAAV) vectors retain the ability...
Snyder, R O, Im, D S, Ni, T, Xiao, X, Samulski, R J, Muzyczka, N
We previously demonstrated that the adeno-associated virus (AAV) Rep68 and Rep78 proteins are able to nick the AAV origin of DNA replication at the terminal resolution site (trs) in an ATP-dependent...
Colocalization of adeno-associated virus Rep and capsid proteins in the nuclei of infected cells.
The mechanism of adeno-associated virus (AAV) DNA replication was characterized both genetically and biochemically. In this study, we used monoclonal and polyclonal antibodies to examine the AAV p5...
Adenovirus provides helper functions that facilitate replication of adeno-associated virus (AAV). Both the adenovirus E1B 55-Mr and E4 34-Mr polypeptides are required for efficient and timely...
Samulski, R J, Chang, L S, Shenk, T
A method is described for the production of recombinant adeno-associated virus (AAV) stocks that contain no detectable wild-type helper AAV. The recombinant viruses contained only the terminal 191...
Hearing, P, Samulski, R J, Wishart, W L, Shenk, T
Adenovirus type 5 deletion mutants that lack portions of their cis-acting DNA encapsidation signal synthesized nearly normal levels of viral DNA and late polypeptides but failed to efficiently...
Samulski, R J, Chang, L S, Shenk, T
A recombinant plasmid carrying an infectious adeno-associated viral genome was constructed that differs in several key respects from previously described recombinants. First, the vector is pEMBL8(+),...
Walsh, C E, Nienhuis, A W, Samulski, R J, Brown, M G, Miller, J L, Young, N S, ...
Fanconi anemia (FA) is a recessive inherited disease characterized by defective DNA repair. FA cells are hypersensitive to DNA cross-linking agents that cause chromosomal instability and cell death....
Srivastava, C H, Samulski, R J, Lu, L, Larsen, S H, Srivastava, A
To facilitate genetic analysis of the human pathogenic parvovirus B19, we constructed a hybrid B19 viral genome in which the defective B19 inverted terminal repeats were replaced with the full-length...
Samulski, R J, Berns, K I, Tan, M, Muzyczka, N
We have cloned intact duplex adeno-associated virus (AAV) DNA into the bacterial plasmid pBR322. The AAV genome could be rescued from the recombinant plasmid by transfection of the plasmid DNA into...
Targeted integration of adeno-associated virus (AAV) into human chromosome 19.
Samulski, R J, Zhu, X, Xiao, X, Brook, J D, Housman, D E, Epstein, N, ...
A key feature in adeno-associated virus (AAV) replication is efficient integration of the viral genome into host cell DNA to establish latency when helper virus is absent. The steps involved in this...