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Pesquisa : E02.095.301.500 [Categoria DeCS]
Referências encontradas : 139 [refinar]
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[PMID]:28153088
[Au] Autor:Kim SJ; Kim JH; Yang B; Jeong JS; Lee SW
[Ad] Endereço:Department of Integrated Life Sciences, Research Institute of Advanced Omics, Dankook University, Yongin 16890, Republic of Korea.
[Ti] Título:Specific and Efficient Regression of Cancers Harboring KRAS Mutation by Targeted RNA Replacement.
[So] Source:Mol Ther;25(2):356-367, 2017 Feb 01.
[Is] ISSN:1525-0024
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mutations in the KRAS gene, which persistently activate RAS function, are most frequently found in many types of human cancers. Here, we proposed and verified a new approach against cancers harboring the KRAS mutation with high cancer selectivity and efficient anti-cancer effects based on targeted RNA replacement. To this end, trans-splicing ribozymes from Tetrahymena group I intron were developed, which can specifically target and reprogram the mutant KRAS G12V transcript to induce therapeutic gene activity in cells. Adenoviral vectors containing the specific ribozymes with downstream suicide gene were constructed and then infection with the adenoviruses specifically downregulated KRAS G12V expression and killed KRAS G12V-harboring cancer cells additively upon pro-drug treatment, but it did not affect the growth of wild-type KRAS-expressing cells. Minimal liver toxicity was noted when the adenoviruses were administered systemically in vivo. Importantly, intratumoral injection of the adenoviruses with pro-drug treatment specifically and significantly impeded the growth of xenografted tumors harboring KRAS G12V through a trans-splicing reaction with the target RNA. In contrast, xenografted tumors harboring wild-type KRAS were not affected by the adenoviruses. Therefore, RNA replacement with a mutant KRAS-targeting trans-splicing ribozyme is a potentially useful therapeutic strategy to combat tumors harboring KRAS mutation.
[Mh] Termos MeSH primário: Mutação
Neoplasias/genética
Neoplasias/patologia
Proteínas Proto-Oncogênicas p21(ras)/genética
RNA/genética
Reparo Gênico Alvo-Dirigido
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Proliferação Celular
Modelos Animais de Doenças
Expressão Gênica
Ordem dos Genes
Vetores Genéticos/genética
Seres Humanos
Masculino
Camundongos
Proteínas Proto-Oncogênicas p21(ras)/metabolismo
RNA/metabolismo
RNA Catalítico/genética
RNA Catalítico/metabolismo
Trans-Splicing
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (KRAS protein, human); 0 (RNA, Catalytic); 63231-63-0 (RNA); EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170204
[St] Status:MEDLINE


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[PMID]:28153086
[Au] Autor:Sweeney CL; Zou J; Choi U; Merling RK; Liu A; Bodansky A; Burkett S; Kim JW; De Ravin SS; Malech HL
[Ad] Endereço:Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA. Electronic address: sweeneyco@nih.gov.
[Ti] Título:Targeted Repair of CYBB in X-CGD iPSCs Requires Retention of Intronic Sequences for Expression and Functional Correction.
[So] Source:Mol Ther;25(2):321-330, 2017 Feb 01.
[Is] ISSN:1525-0024
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:X-linked chronic granulomatous disease (X-CGD) is an immune deficiency resulting from defective production of microbicidal reactive oxygen species (ROS) by phagocytes. Causative mutations occur throughout the CYBB gene, resulting in absent or defective gp91 protein expression. To correct CYBB exon 5 mutations while retaining normal gene regulation, we utilized TALEN or Cas9 for exon 5 replacement in induced pluripotent stem cells (iPSCs) from patients, which restored gp91 expression and ROS production in iPSC-derived granulocytes. Alternate approaches for correcting the majority of X-CGD mutations were assessed, involving TALEN- or Cas9-mediated insertion of CYBB minigenes at exon 1 or 2 of the CYBB locus. Targeted insertion of an exon 1-13 minigene into CYBB exon 1 resulted in no detectable gp91 expression or ROS activity in iPSC-derived granulocytes. In contrast, targeted insertion of an exon 2-13 minigene into exon 2 restored both gp91 and ROS activity. This demonstrates the efficacy of two correction strategies: seamless repair of specific CYBB mutations by exon replacement or targeted insertion of an exon 2-13 minigene to CYBB exon 2 while retaining exon/intron 1. Furthermore, it highlights a key issue for targeted insertion strategies for expression from an endogenous promoter: retention of intronic elements can be necessary for expression.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica
Doença Granulomatosa Crônica/genética
Doença Granulomatosa Crônica/metabolismo
Células-Tronco Pluripotentes Induzidas/metabolismo
Íntrons
Glicoproteínas de Membrana/genética
NADPH Oxidases/genética
Reparo Gênico Alvo-Dirigido
[Mh] Termos MeSH secundário: Diferenciação Celular/genética
Linhagem Celular
Éxons
Edição de Genes
Ordem dos Genes
Marcação de Genes
Técnicas de Transferência de Genes
Loci Gênicos
Vetores Genéticos
Granulócitos/citologia
Granulócitos/metabolismo
Doença Granulomatosa Crônica/terapia
Seres Humanos
Mutação
NADPH Oxidase 2
Transgenes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Membrane Glycoproteins); EC 1.6.3.- (CYBB protein, human); EC 1.6.3.- (NADPH Oxidase 2); EC 1.6.3.- (NADPH Oxidases)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170204
[St] Status:MEDLINE


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[PMID]:28109959
[Au] Autor:Ruan GX; Barry E; Yu D; Lukason M; Cheng SH; Scaria A
[Ad] Endereço:Rare Diseases, Sanofi Genzyme, Framingham, MA 01701, USA. Electronic address: guoxiang.ruan@genzyme.com.
[Ti] Título:CRISPR/Cas9-Mediated Genome Editing as a Therapeutic Approach for Leber Congenital Amaurosis 10.
[So] Source:Mol Ther;25(2):331-341, 2017 Feb 01.
[Is] ISSN:1525-0024
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:As the most common subtype of Leber congenital amaurosis (LCA), LCA10 is a severe retinal dystrophy caused by mutations in the CEP290 gene. The most frequent mutation found in patients with LCA10 is a deep intronic mutation in CEP290 that generates a cryptic splice donor site. The large size of the CEP290 gene prevents its use in adeno-associated virus (AAV)-mediated gene augmentation therapy. Here, we show that targeted genomic deletion using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system represents a promising therapeutic approach for the treatment of patients with LCA10 bearing the CEP290 splice mutation. We generated a cellular model of LCA10 by introducing the CEP290 splice mutation into 293FT cells and we showed that guide RNA pairs coupled with SpCas9 were highly efficient at removing the intronic splice mutation and restoring the expression of wild-type CEP290. In addition, we demonstrated that a dual AAV system could effectively delete an intronic fragment of the Cep290 gene in the mouse retina. To minimize the immune response to prolonged expression of SpCas9, we developed a self-limiting CRISPR/Cas9 system that minimizes the duration of SpCas9 expression. These results support further studies to determine the therapeutic potential of CRISPR/Cas9-based strategies for the treatment of patients with LCA10.
[Mh] Termos MeSH primário: Sistemas CRISPR-Cas
Edição de Genes
Amaurose Congênita de Leber/genética
[Mh] Termos MeSH secundário: Processamento Alternativo
Animais
Antígenos de Neoplasias/genética
Feminino
Expressão Gênica
Ordem dos Genes
Marcação de Genes
Loci Gênicos
Íntrons
Amaurose Congênita de Leber/terapia
Camundongos
Mutação
Proteínas de Neoplasias/genética
RNA Guia
RNA Mensageiro/genética
Retina/metabolismo
Deleção de Sequência
Reparo Gênico Alvo-Dirigido
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Neoplasm); 0 (Cep290 protein, human); 0 (Neoplasm Proteins); 0 (RNA, Guide); 0 (RNA, Messenger)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170123
[St] Status:MEDLINE


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[PMID]:27406980
[Au] Autor:Hoban MD; Lumaquin D; Kuo CY; Romero Z; Long J; Ho M; Young CS; Mojadidi M; Fitz-Gibbon S; Cooper AR; Lill GR; Urbinati F; Campo-Fernandez B; Bjurstrom CF; Pellegrini M; Hollis RP; Kohn DB
[Ad] Endereço:Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California USA.
[Ti] Título:CRISPR/Cas9-Mediated Correction of the Sickle Mutation in Human CD34+ cells.
[So] Source:Mol Ther;24(9):1561-9, 2016 Sep.
[Is] ISSN:1525-0024
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Targeted genome editing technology can correct the sickle cell disease mutation of the ß-globin gene in hematopoietic stem cells. This correction supports production of red blood cells that synthesize normal hemoglobin proteins. Here, we demonstrate that Transcription Activator-Like Effector Nucleases (TALENs) and the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 nuclease system can target DNA sequences around the sickle-cell mutation in the ß-globin gene for site-specific cleavage and facilitate precise correction when a homologous donor template is codelivered. Several pairs of TALENs and multiple CRISPR guide RNAs were evaluated for both on-target and off-target cleavage rates. Delivery of the CRISPR/Cas9 components to CD34+ cells led to over 18% gene modification in vitro. Additionally, we demonstrate the correction of the sickle cell disease mutation in bone marrow derived CD34+ hematopoietic stem and progenitor cells from sickle cell disease patients, leading to the production of wild-type hemoglobin. These results demonstrate correction of the sickle mutation in patient-derived CD34+ cells using CRISPR/Cas9 technology.
[Mh] Termos MeSH primário: Anemia Falciforme/genética
Sistemas CRISPR-Cas
Edição de Genes
Células-Tronco Hematopoéticas/metabolismo
Mutação
Reparo Gênico Alvo-Dirigido
Globinas beta/genética
[Mh] Termos MeSH secundário: Anemia Falciforme/terapia
Sequência de Bases
Linhagem Celular
Clivagem do DNA
Marcação de Genes
Loci Gênicos
Seres Humanos
Ligação Proteica
RNA Guia
Nucleases dos Efetores Semelhantes a Ativadores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Guide); 0 (beta-Globins); EC 3.1.- (Transcription Activator-Like Effector Nucleases)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170902
[Lr] Data última revisão:
170902
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160714
[St] Status:MEDLINE
[do] DOI:10.1038/mt.2016.148


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[PMID]:27352592
[Au] Autor:Nau JY
[Ti] Título:[Not Available].
[Ti] Título:DERNIÈRES NOUVELLES DU FRONT DE LA RÉÉDITION DES GÉNOMES HUMAINS..
[So] Source:Rev Med Suisse;12(518):954-5, 2016 May 11.
[Is] ISSN:1660-9379
[Cp] País de publicação:Switzerland
[La] Idioma:fre
[Mh] Termos MeSH primário: Pesquisa em Genética/legislação & jurisprudência
Terapia Genética/legislação & jurisprudência
Genoma Humano
[Mh] Termos MeSH secundário: Academias e Institutos/legislação & jurisprudência
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética
Epigênese Genética
União Europeia
França
Seres Humanos
Distrofia Muscular de Duchenne/genética
Reparo Gênico Alvo-Dirigido/legislação & jurisprudência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1608
[Cu] Atualização por classe:160629
[Lr] Data última revisão:
160629
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160630
[St] Status:MEDLINE


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[PMID]:27314455
[Au] Autor:Lee TW; Southern KW; Perry LA; Penny-Dimri JC; Aslam AA
[Ad] Endereço:Leeds Regional Paediatric Cystic Fibrosis Centre, A Floor, Clarendon Wing, Leeds General Infirmary, Great George Street, Leeds, West Yorkshire, UK, LS1 3EX.
[Ti] Título:Topical cystic fibrosis transmembrane conductance regulator gene replacement for cystic fibrosis-related lung disease.
[So] Source:Cochrane Database Syst Rev;(6):CD005599, 2016 Jun 17.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Cystic fibrosis is caused by a defective gene encoding a protein called the cystic fibrosis transmembrane conductance regulator (CFTR), and is characterised by chronic lung infection resulting in inflammation and progressive lung damage that results in a reduced life expectancy. OBJECTIVES: To determine whether topical CFTR gene replacement therapy to the lungs in people with cystic fibrosis is associated with improvements in clinical outcomes, and to assess any adverse effects. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings.Date of most recent search: 05 May 2016.An additional search of the National Institutes for Health (NIH) Genetic Modification Clinical Research Information System (GeMCRIS) was also performed for the years 1992 to 2015.Date of most recent search: 20 April 2016. SELECTION CRITERIA: Randomised controlled studies comparing topical CFTR gene delivery to the lung, using either viral or non-viral delivery systems, with placebo or an alternative delivery system in people with confirmed cystic fibrosis. DATA COLLECTION AND ANALYSIS: The authors independently extracted data and assessed study quality. Authors of included studies were contacted and asked for any available additional data. Meta-analysis was limited due to differing study designs. MAIN RESULTS: Four randomised controlled studies met the inclusion criteria for this review, involving a total of 302 participants lasting from 29 days to 13 months; 14 studies were excluded. The included studies differed in terms of CFTR gene replacement agent and study design, which limited the meta-analysis. One study only enrolled adult males, the remaining studies included both males and females aged 12 years and over.Risk of bias in the studies was moderate. Random sequence generation and allocation concealment was only described in the more recent study; the remaining three studies were judged to have an unclear risk of bias. All four studies documented double-blinding to the intervention, but there is some uncertainty with regards to participant blinding in one study. Some outcome data were missing from all four studies.There were no differences in either the number of respiratory exacerbations or the number of participants with an exacerbation between replacement therapy or placebo groups at any time point. Meta-analysis of most respiratory function tests showed no difference between treatment and placebo groups, but the smallest study (n = 16) reported forced vital capacity (litres) increased more in the placebo group at up to 24 hours. A further study reported a significant improvement in forced expiratory volume at one second (litres) at 30 days after participants had received their first dose of favouring the gene therapy agent, but this finding was not confirmed when combined with at second study in the meta-analysis. The more recent study (n = 140) demonstrated a small improvement in forced vital capacity (per cent predicted) at two and three months and again at 11 and 12 months for participants receiving CFTR gene replacement therapy compared to those receiving placebo. The same study reported a significant difference in the relative change in forced expiratory volume at one second (per cent predicted) at two months, three months and 12 months.One small study reported significant concerns with "influenza-like" symptoms in participants treated with CFTR gene replacement therapy; this was not reported on repeated use of the same agent in a larger recent study.There was no other evidence of positive impact on outcomes, in particular improved quality of life or reduced treatment burden.Two studies measured ion transport in the lower airways; one (n = 16) demonstrated significant changes toward normal values in the participants who received gene transfer agents (P < 0.0001), mean difference 6.86 (95% confidence interval 3.77 to 9.95). The second study (n = 140) also reported significant changes toward normal values (P = 0.032); however, aggregate data were not available for analysis. In the most recent study, there was also evidence of increased salt transport in cells obtained by brushing the lower airway. These outcomes, whilst important, are not of direct clinical relevance. AUTHORS' CONCLUSIONS: One study of liposome-based CFTR gene transfer therapy demonstrated some improvements in respiratory function in people with CF, but this limited evidence of efficacy does not support this treatment as a routine therapy at present. There was no evidence of efficacy for viral-mediated gene delivery.Future studies need to investigate clinically important outcome measures.
[Mh] Termos MeSH primário: Regulador de Condutância Transmembrana em Fibrose Cística/genética
Fibrose Cística/terapia
Reparo Gênico Alvo-Dirigido/métodos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Fibrose Cística/genética
Regulador de Condutância Transmembrana em Fibrose Cística/uso terapêutico
Feminino
Técnicas de Transferência de Genes
Terapia Genética/efeitos adversos
Terapia Genética/métodos
Seres Humanos
Lipossomos
Masculino
Ensaios Clínicos Controlados Aleatórios como Assunto
Testes de Função Respiratória
Reparo Gênico Alvo-Dirigido/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Liposomes); 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:160701
[Lr] Data última revisão:
160701
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160618
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD005599.pub5


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[PMID]:27253876
[Au] Autor:Kamiya H; Nishigaki N; Ikeda A; Yukawa S; Morita Y; Nakatsu Y; Tsuzuki T; Harashima H
[Ad] Endereço:a Graduate School of Science and Engineering, Ehime University , Matsuyama , Japan.
[Ti] Título:Insertion and Deletion Mismatches Distant from the Target Position Improve Gene Correction with a Tailed Duplex.
[So] Source:Nucleosides Nucleotides Nucleic Acids;35(7):379-88, 2016 Jul 02.
[Is] ISSN:1532-2335
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A 5'-tailed duplex (TD) DNA corrects a base-substitution mutation. In this study, the effects of insertion and deletion (indel) mismatches distant from the target position on the gene correction were examined. Three target plasmid DNAs with and without indel mismatches ∼330 bases distant from the correction target position were prepared, and introduced into HeLa cells together with the TD. The indel mismatches improved the gene correction efficiency and specificity without sequence conversions at the indel mismatch site. These results suggested that the gene correction efficiency and specificity are increased when an appropriate second mismatch is introduced into the TD fragment.
[Mh] Termos MeSH primário: Pareamento Incorreto de Bases
Mutação INDEL
Reparo Gênico Alvo-Dirigido/métodos
[Mh] Termos MeSH secundário: Sequência de Bases
Reparo de Erro de Pareamento de DNA
Células HeLa
Seres Humanos
Plasmídeos/genética
Análise de Sequência de DNA
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170303
[Lr] Data última revisão:
170303
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160603
[St] Status:MEDLINE
[do] DOI:10.1080/15257770.2016.1163384


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[PMID]:27180109
[Au] Autor:Burger G
[Ad] Endereço:Department of Biochemistry, Robert-Cedergren Centre for Bioinformatics and Genomics, Université de Montréal, Montréal, Canada. Electronic address: Gertraud.Burger@umontreal.ca.
[Ti] Título:Non-functional genes repaired at the RNA level.
[So] Source:C R Biol;339(7-8):289-95, 2016 Jul-Aug.
[Is] ISSN:1768-3238
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Genomes and genes continuously evolve. Gene sequences undergo substitutions, deletions or nucleotide insertions; mobile genetic elements invade genomes and interleave in genes; chromosomes break, even within genes, and pieces reseal in reshuffled order. To maintain functional gene products and assure an organism's survival, two principal strategies are used - either repair of the gene itself or of its product. I will introduce common types of gene aberrations and how gene function is restored secondarily, and then focus on systematically fragmented genes found in a poorly studied protist group, the diplonemids. Expression of their broken genes involves restitching of pieces at the RNA-level, and substantial RNA editing, to compensate for point mutations. I will conclude with thoughts on how such a grotesquely unorthodox system may have evolved, and why this group of organisms persists and thrives since tens of millions of years.
[Mh] Termos MeSH primário: Evolução Biológica
Genética/tendências
RNA/genética
[Mh] Termos MeSH secundário: Animais
Fragmentação do DNA
Genes Mitocondriais/genética
Seres Humanos
Edição de RNA
Reparo Gênico Alvo-Dirigido
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
63231-63-0 (RNA)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170223
[Lr] Data última revisão:
170223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160516
[St] Status:MEDLINE


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[PMID]:27166877
[Au] Autor:Rao DD; Jay C; Wang Z; Luo X; Kumar P; Eysenbach H; Ghisoli M; Senzer N; Nemunaitis J
[Ad] Endereço:Strike Bio, Carrollton, Texas, USA.
[Ti] Título:Preclinical Justification of pbi-shRNA EWS/FLI1 Lipoplex (LPX) Treatment for Ewing's Sarcoma.
[So] Source:Mol Ther;24(8):1412-22, 2016 Aug.
[Is] ISSN:1525-0024
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The EWS/FLI1 fusion gene is well characterized as a driver of Ewing's sarcoma. Bi-shRNA EWS/FLI1 is a functional plasmid DNA construct that transcribes both siRNA and miRNA-like effectors each of which targets the identical type 1 translocation junction region of the EWS/FLI1 transcribed mRNA sequence. Previous preclinical and clinical studies confirm the safety of this RNA interference platform technology and consistently demonstrate designated mRNA and protein target knockdown at greater than 90% efficiency. We initiated development of pbi-shRNA EWS/FLI1 lipoplex (LPX) for the treatment of type 1 Ewing's sarcoma. Clinical-grade plasmid was manufactured and both sequence and activity verified. Target protein and RNA knockdown of 85-92% was demonstrated in vitro in type 1 human Ewing's sarcoma tumor cell lines with the optimal bi-shRNA EWS/FLI1 plasmid. This functional plasmid was placed in a clinically tested, liposomal (LP) delivery vehicle followed by in vivo verification of activity. Type 1 Ewing's sarcoma xenograft modeling confirmed dose related safety and tumor response to pbi-shRNA EWS/FLI1 LPX. Toxicology studies in mini-pigs with doses comparable to the demonstrated in vivo efficacy dose resulted in transient fever, occasional limited hypertension at low- and high-dose assessment and transient liver enzyme elevation at high dose. These results provide the justification to initiate clinical testing.
[Mh] Termos MeSH primário: Lipossomos
Proteínas de Fusão Oncogênicas/genética
Proteína Proto-Oncogênica c-fli-1/genética
RNA Interferente Pequeno/genética
Proteína EWS de Ligação a RNA/genética
Sarcoma de Ewing/genética
[Mh] Termos MeSH secundário: Animais
Sítios de Ligação
Linhagem Celular Tumoral
Citocinas/metabolismo
Modelos Animais de Doenças
Avaliação Pré-Clínica de Medicamentos
Feminino
Técnicas de Silenciamento de Genes
Ordem dos Genes
Terapia Genética
Seres Humanos
Mediadores da Inflamação
Masculino
Proteínas de Fusão Oncogênicas/administração & dosagem
Proteínas de Fusão Oncogênicas/química
Plasmídeos/administração & dosagem
Plasmídeos/genética
Proteína Proto-Oncogênica c-fli-1/administração & dosagem
Proteína Proto-Oncogênica c-fli-1/química
Interferência de RNA
RNA Interferente Pequeno/administração & dosagem
RNA Interferente Pequeno/química
Proteína EWS de Ligação a RNA/administração & dosagem
Proteína EWS de Ligação a RNA/química
Sarcoma de Ewing/mortalidade
Sarcoma de Ewing/patologia
Sarcoma de Ewing/terapia
Reparo Gênico Alvo-Dirigido
Transfecção
Carga Tumoral
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines); 0 (EWS-FLI fusion protein); 0 (Inflammation Mediators); 0 (Liposomes); 0 (Oncogene Proteins, Fusion); 0 (Proto-Oncogene Protein c-fli-1); 0 (RNA, Small Interfering); 0 (RNA-Binding Protein EWS)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160512
[St] Status:MEDLINE
[do] DOI:10.1038/mt.2016.93


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[PMID]:27153210
[Au] Autor:Ward P; Walsh CE
[Ad] Endereço:a Tisch Cancer Institute , Icahn School of Medicine at Mount Sinai, One Gustave Levy Place , New York City , NY , USA.
[Ti] Título:Current and future prospects for hemophilia gene therapy.
[So] Source:Expert Rev Hematol;9(7):649-59, 2016 Jul.
[Is] ISSN:1747-4094
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Here we review the recent literature on Hemophilia gene transfer/therapy. Gene therapy is one of several new technologies being developed as a treatment for bleeding disorders. We will discuss current and pending clinical efforts and attempt to relate how the field is trending. In doing so, we will focus on the use of recombinant Adeno-associated viral (rAAV) vector-mediated gene transfer since all currently active trials are using this vector. Recent exciting results embody nearly 20 years of preclinical and translational research. After several early clinical attempts, therapeutic factor levels that can now be achieved reflect several modifications of the original vectors. Patterns of results are slowly starting to emerge as different AAV vectors are being tested. As with any new technology, there are drawbacks, and the potential for immune/inflammatory and oncogenic risks have emerged and will be discussed.
[Mh] Termos MeSH primário: Terapia Genética
Hemofilia A/genética
Hemofilia A/terapia
Hemofilia B/genética
Hemofilia B/terapia
[Mh] Termos MeSH secundário: Animais
Ensaios Clínicos como Assunto
Dependovirus/classificação
Dependovirus/genética
Avaliação Pré-Clínica de Medicamentos
Fator IX/genética
Fator VIII/genética
Edição de Genes
Marcação de Genes
Técnicas de Transferência de Genes
Terapia Genética/métodos
Vetores Genéticos/efeitos adversos
Vetores Genéticos/genética
Seres Humanos
Reparo Gênico Alvo-Dirigido
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
9001-27-8 (Factor VIII); 9001-28-9 (Factor IX)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170518
[Lr] Data última revisão:
170518
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160507
[St] Status:MEDLINE
[do] DOI:10.1080/17474086.2016.1182859



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