The Experts below are selected from a list of 10245 Experts worldwide ranked by ideXlab platform
Masafumi Matsuo - One of the best experts on this subject based on the ideXlab platform.
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Chimeric RNA ethylene bridged nucleic acids promote dystrophin expression in myocytes of duchenne muscular dystrophy by inducing skipping of the nonsense mutation encoding exon
Human Gene Therapy, 2004Co-Authors: Agus Surono, Tran Van Khanh, Makoto Koizumi, Miho Takagi, Yasuhiro Takeshima, Hiroko Wada, Mariko Yagi, Masafumi MatsuoAbstract:Editing of dystrophin mRNA by induction of exon skipping, using antisense oligonucleotides, has been proposed as one way to generate dystrophin expression in Duchenne muscular dystrophy (DMD) patients. Here, antisense Chimeric oligonucleotides consisting of RNA and a new modified nucleic acid are tested for activity to induce skipping of an exon containing a nonsense mutation. In a Japanese DMD case, a nonsense mutation (R1967X) due to a single nucleotide change in exon 41 of the dystrophin gene (C5899T) was identified. Oligonucleotides consisting of 2′-O-methyl RNA and a new 2′-O,4′-C-ethylene-bridged nucleic acid (ENA) were designed to bind the mutation site of exon 41, and their ability to induce exon 41 skipping in dystrophin mRNA was evaluated. Finally, among the specific oligonucleotides tested, an 18-mer RNA/ENA chimera was found to have the strongest activity, inducing exon 41 skipping in nearly 90% of dystrophin mRNA. Accordingly, nearly 90% of cultured myocytes were shown to be dystrophin positi...
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Chimeric RNA ethylene bridged nucleic acids promote dystrophin expression in myocytes of duchenne muscular dystrophy by inducing skipping of the nonsense mutation encoding exon
Human Gene Therapy, 2004Co-Authors: Agus Surono, Makoto Koizumi, Miho Takagi, Yasuhiro Takeshima, Hiroko Wada, Mariko Yagi, Tran Van Khanh, Masafumi MatsuoAbstract:Editing of dystrophin mRNA by induction of exon skipping, using antisense oligonucleotides, has been proposed as one way to generate dystrophin expression in Duchenne muscular dystrophy (DMD) patients. Here, antisense Chimeric oligonucleotides consisting of RNA and a new modified nucleic acid are tested for activity to induce skipping of an exon containing a nonsense mutation. In a Japanese DMD case, a nonsense mutation (R1967X) due to a single nucleotide change in exon 41 of the dystrophin gene (C5899T) was identified. Oligonucleotides consisting of 2'-O-methyl RNA and a new 2'-O,4'-C-ethylene-bridged nucleic acid (ENA) were designed to bind the mutation site of exon 41, and their ability to induce exon 41 skipping in dystrophin mRNA was evaluated. Finally, among the specific oligonucleotides tested, an 18-mer RNA/ENA chimera was found to have the strongest activity, inducing exon 41 skipping in nearly 90% of dystrophin mRNA. Accordingly, nearly 90% of cultured myocytes were shown to be dystrophin positive by immunohistochemical analysis. Western blot analysis disclosed the presence of nearly normal-sized dystrophin up to 1 week after the transfection. Our results suggest that an RNA/ENA chimera can be used to express dystrophin in DMD.
Agus Surono - One of the best experts on this subject based on the ideXlab platform.
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Chimeric RNA ethylene bridged nucleic acids promote dystrophin expression in myocytes of duchenne muscular dystrophy by inducing skipping of the nonsense mutation encoding exon
Human Gene Therapy, 2004Co-Authors: Agus Surono, Tran Van Khanh, Makoto Koizumi, Miho Takagi, Yasuhiro Takeshima, Hiroko Wada, Mariko Yagi, Masafumi MatsuoAbstract:Editing of dystrophin mRNA by induction of exon skipping, using antisense oligonucleotides, has been proposed as one way to generate dystrophin expression in Duchenne muscular dystrophy (DMD) patients. Here, antisense Chimeric oligonucleotides consisting of RNA and a new modified nucleic acid are tested for activity to induce skipping of an exon containing a nonsense mutation. In a Japanese DMD case, a nonsense mutation (R1967X) due to a single nucleotide change in exon 41 of the dystrophin gene (C5899T) was identified. Oligonucleotides consisting of 2′-O-methyl RNA and a new 2′-O,4′-C-ethylene-bridged nucleic acid (ENA) were designed to bind the mutation site of exon 41, and their ability to induce exon 41 skipping in dystrophin mRNA was evaluated. Finally, among the specific oligonucleotides tested, an 18-mer RNA/ENA chimera was found to have the strongest activity, inducing exon 41 skipping in nearly 90% of dystrophin mRNA. Accordingly, nearly 90% of cultured myocytes were shown to be dystrophin positi...
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Chimeric RNA ethylene bridged nucleic acids promote dystrophin expression in myocytes of duchenne muscular dystrophy by inducing skipping of the nonsense mutation encoding exon
Human Gene Therapy, 2004Co-Authors: Agus Surono, Makoto Koizumi, Miho Takagi, Yasuhiro Takeshima, Hiroko Wada, Mariko Yagi, Tran Van Khanh, Masafumi MatsuoAbstract:Editing of dystrophin mRNA by induction of exon skipping, using antisense oligonucleotides, has been proposed as one way to generate dystrophin expression in Duchenne muscular dystrophy (DMD) patients. Here, antisense Chimeric oligonucleotides consisting of RNA and a new modified nucleic acid are tested for activity to induce skipping of an exon containing a nonsense mutation. In a Japanese DMD case, a nonsense mutation (R1967X) due to a single nucleotide change in exon 41 of the dystrophin gene (C5899T) was identified. Oligonucleotides consisting of 2'-O-methyl RNA and a new 2'-O,4'-C-ethylene-bridged nucleic acid (ENA) were designed to bind the mutation site of exon 41, and their ability to induce exon 41 skipping in dystrophin mRNA was evaluated. Finally, among the specific oligonucleotides tested, an 18-mer RNA/ENA chimera was found to have the strongest activity, inducing exon 41 skipping in nearly 90% of dystrophin mRNA. Accordingly, nearly 90% of cultured myocytes were shown to be dystrophin positive by immunohistochemical analysis. Western blot analysis disclosed the presence of nearly normal-sized dystrophin up to 1 week after the transfection. Our results suggest that an RNA/ENA chimera can be used to express dystrophin in DMD.
William S Hayward - One of the best experts on this subject based on the ideXlab platform.
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bic a novel gene activated by proviral insertions in avian leukosis virus induced lymphomas is likely to function through its noncoding RNA
Molecular and Cellular Biology, 1997Co-Authors: Wayne Tam, D Benyehuda, William S HaywardAbstract:The bic locus is a common retroviral integration site in avian leukosis virus (ALV)-induced B-cell lymphomas originally identified by infection of chickens with ALVs of two different subgroups (Clurman and Hayward, Mol. Cell. Biol. 9:2657-2664, 1989). Based on its frequent association with c-myc activation and its preferential activation in metastatic tumors, the bic locus is thought to harbor a gene that can collaborate with c-myc in lymphomagenesis and presumably plays a role in late stages of tumor progression. In the present study, we have cloned and characterized two novel genes, bdw and bic, at the bic locus. bdw encoded a putative novel protein of 345 amino acids. However, its expression did not appear to be altered in tumor tissues, suggesting that it is not involved in oncogenesis. The bic gene consisted of two exons and was expressed as two spliced and alteRNAtively polyadenylated transcripts at low levels in lymphoid/hematopoietic tissues. In tumors harboring bic integrations, proviruses drove bic gene expression by promoter insertion, resulting in high levels of expression of a Chimeric RNA containing bic exon 2. Interestingly, bic lacked an extensive open reading frame, implying that it may function through its RNA. Computer analysis of RNA from small exon 2 of bic predicted extensive double-stranded structures, including a highly ordered RNA duplex between nucleotides 316 and 461. The possible role of bic in cell growth and differentiation is discussed in view of the emerging evidence that untranslated RNAs play a role in growth control.
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bic a novel gene activated by proviral insertions in avian leukosis virus induced lymphomas is likely to function through its noncoding RNA
Molecular and Cellular Biology, 1997Co-Authors: D Benyehuda, William S HaywardAbstract:Thebiclocus is a common retroviral integration site in avian leukosis virus (ALV)-induced B-cell lymphomasoriginallyidentifiedbyinfectionofchickenswithALVsoftwodifferentsubgroups(ClurmanandHayward, Mol. Cell. Biol. 9:2657‐2664, 1989). Based on its frequent association with c-mycactivation and its preferential activation in metastatic tumors, the bic locus is thought to harbor a gene that can collaborate with c-myc in lymphomagenesis and presumably plays a role in late stages of tumor progression. In the present study, we have cloned and characterized two novel genes, bdw and bic ,a t thebic locus. bdw encoded a putative novel protein of 345 amino acids. However, its expression did not appear to be altered in tumor tissues, suggesting that it is not involved in oncogenesis. Thebicgene consisted of two exons and was expressed as two spliced and alteRNAtively polyadenylated transcripts at low levels in lymphoid/hematopoietic tissues. In tumors harboring bic integrations, proviruses drove bic gene expression by promoter insertion, resulting in high levels of expression of a Chimeric RNA containingbicexon 2. Interestingly,biclacked an extensive open reading frame, implying that it may function through its RNA. Computer analysis of RNA from small exon 2 ofbicpredicted extensivedouble-strandedstructures,includingahighlyorderedRNAduplexbetweennucleotides316and461. The possible role of bic in cell growth and differentiation is discussed in view of the emerging evidence that untranslated RNAs play a role in growth control. The proto-oncogene c-mycplays a critical role in the development of lymphomas in birds and mammals (16, 48). Experiments in both the murine and avian systems indicate that activationofc-mycaloneisnotsufficientforfullmalignancy.In Em-c-myc transgenic mice, monoclonal lymphomas develop only after a variable and relatively long latency (2), suggesting that additional genetic alterations besides c-myc are required to induce full-blown lymphomas. Consistent with this notion,
Hiroko Wada - One of the best experts on this subject based on the ideXlab platform.
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Chimeric RNA ethylene bridged nucleic acids promote dystrophin expression in myocytes of duchenne muscular dystrophy by inducing skipping of the nonsense mutation encoding exon
Human Gene Therapy, 2004Co-Authors: Agus Surono, Tran Van Khanh, Makoto Koizumi, Miho Takagi, Yasuhiro Takeshima, Hiroko Wada, Mariko Yagi, Masafumi MatsuoAbstract:Editing of dystrophin mRNA by induction of exon skipping, using antisense oligonucleotides, has been proposed as one way to generate dystrophin expression in Duchenne muscular dystrophy (DMD) patients. Here, antisense Chimeric oligonucleotides consisting of RNA and a new modified nucleic acid are tested for activity to induce skipping of an exon containing a nonsense mutation. In a Japanese DMD case, a nonsense mutation (R1967X) due to a single nucleotide change in exon 41 of the dystrophin gene (C5899T) was identified. Oligonucleotides consisting of 2′-O-methyl RNA and a new 2′-O,4′-C-ethylene-bridged nucleic acid (ENA) were designed to bind the mutation site of exon 41, and their ability to induce exon 41 skipping in dystrophin mRNA was evaluated. Finally, among the specific oligonucleotides tested, an 18-mer RNA/ENA chimera was found to have the strongest activity, inducing exon 41 skipping in nearly 90% of dystrophin mRNA. Accordingly, nearly 90% of cultured myocytes were shown to be dystrophin positi...
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Chimeric RNA ethylene bridged nucleic acids promote dystrophin expression in myocytes of duchenne muscular dystrophy by inducing skipping of the nonsense mutation encoding exon
Human Gene Therapy, 2004Co-Authors: Agus Surono, Makoto Koizumi, Miho Takagi, Yasuhiro Takeshima, Hiroko Wada, Mariko Yagi, Tran Van Khanh, Masafumi MatsuoAbstract:Editing of dystrophin mRNA by induction of exon skipping, using antisense oligonucleotides, has been proposed as one way to generate dystrophin expression in Duchenne muscular dystrophy (DMD) patients. Here, antisense Chimeric oligonucleotides consisting of RNA and a new modified nucleic acid are tested for activity to induce skipping of an exon containing a nonsense mutation. In a Japanese DMD case, a nonsense mutation (R1967X) due to a single nucleotide change in exon 41 of the dystrophin gene (C5899T) was identified. Oligonucleotides consisting of 2'-O-methyl RNA and a new 2'-O,4'-C-ethylene-bridged nucleic acid (ENA) were designed to bind the mutation site of exon 41, and their ability to induce exon 41 skipping in dystrophin mRNA was evaluated. Finally, among the specific oligonucleotides tested, an 18-mer RNA/ENA chimera was found to have the strongest activity, inducing exon 41 skipping in nearly 90% of dystrophin mRNA. Accordingly, nearly 90% of cultured myocytes were shown to be dystrophin positive by immunohistochemical analysis. Western blot analysis disclosed the presence of nearly normal-sized dystrophin up to 1 week after the transfection. Our results suggest that an RNA/ENA chimera can be used to express dystrophin in DMD.
Yasuhiro Takeshima - One of the best experts on this subject based on the ideXlab platform.
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Chimeric RNA ethylene bridged nucleic acids promote dystrophin expression in myocytes of duchenne muscular dystrophy by inducing skipping of the nonsense mutation encoding exon
Human Gene Therapy, 2004Co-Authors: Agus Surono, Tran Van Khanh, Makoto Koizumi, Miho Takagi, Yasuhiro Takeshima, Hiroko Wada, Mariko Yagi, Masafumi MatsuoAbstract:Editing of dystrophin mRNA by induction of exon skipping, using antisense oligonucleotides, has been proposed as one way to generate dystrophin expression in Duchenne muscular dystrophy (DMD) patients. Here, antisense Chimeric oligonucleotides consisting of RNA and a new modified nucleic acid are tested for activity to induce skipping of an exon containing a nonsense mutation. In a Japanese DMD case, a nonsense mutation (R1967X) due to a single nucleotide change in exon 41 of the dystrophin gene (C5899T) was identified. Oligonucleotides consisting of 2′-O-methyl RNA and a new 2′-O,4′-C-ethylene-bridged nucleic acid (ENA) were designed to bind the mutation site of exon 41, and their ability to induce exon 41 skipping in dystrophin mRNA was evaluated. Finally, among the specific oligonucleotides tested, an 18-mer RNA/ENA chimera was found to have the strongest activity, inducing exon 41 skipping in nearly 90% of dystrophin mRNA. Accordingly, nearly 90% of cultured myocytes were shown to be dystrophin positi...
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Chimeric RNA ethylene bridged nucleic acids promote dystrophin expression in myocytes of duchenne muscular dystrophy by inducing skipping of the nonsense mutation encoding exon
Human Gene Therapy, 2004Co-Authors: Agus Surono, Makoto Koizumi, Miho Takagi, Yasuhiro Takeshima, Hiroko Wada, Mariko Yagi, Tran Van Khanh, Masafumi MatsuoAbstract:Editing of dystrophin mRNA by induction of exon skipping, using antisense oligonucleotides, has been proposed as one way to generate dystrophin expression in Duchenne muscular dystrophy (DMD) patients. Here, antisense Chimeric oligonucleotides consisting of RNA and a new modified nucleic acid are tested for activity to induce skipping of an exon containing a nonsense mutation. In a Japanese DMD case, a nonsense mutation (R1967X) due to a single nucleotide change in exon 41 of the dystrophin gene (C5899T) was identified. Oligonucleotides consisting of 2'-O-methyl RNA and a new 2'-O,4'-C-ethylene-bridged nucleic acid (ENA) were designed to bind the mutation site of exon 41, and their ability to induce exon 41 skipping in dystrophin mRNA was evaluated. Finally, among the specific oligonucleotides tested, an 18-mer RNA/ENA chimera was found to have the strongest activity, inducing exon 41 skipping in nearly 90% of dystrophin mRNA. Accordingly, nearly 90% of cultured myocytes were shown to be dystrophin positive by immunohistochemical analysis. Western blot analysis disclosed the presence of nearly normal-sized dystrophin up to 1 week after the transfection. Our results suggest that an RNA/ENA chimera can be used to express dystrophin in DMD.