Gene therapy and regulation最新文献_第2页

FROM TETRAPLOID-COMPLEMENTING MOUSE ıPS CELLS TO FULLY PLURIPOTENT PATIENT-SPECIFIC iPS CELLS 从四倍体互补小鼠ıPS细胞到完全多能的患者特异性iPS细胞

Gene therapy and regulation Pub Date : 2011-11-20 DOI: 10.1142/S156855861000015X

Wei Li, Liu Wang, Lei Liu, Xiao-Yang Zhao, F. Zeng, Qi Zhou

引用次数: 0

CARDINAL REGENERATIVE FEATURES OF THE MRL MOUSE — AN UPDATE MRL小鼠的主要再生特征-一个更新

Gene therapy and regulation Pub Date : 2011-11-20 DOI: 10.1142/S1568558611000246

L. Arthur, P. Sachadyn, Dmitri Gourevitch, E. Heber-Katz

引用次数: 0

Erratum: A new recombinant adeno-associated virus (AAV)-based random peptide display library system: Infection-defective AAV1.9-3 as a novel detargeted platform for vector evolution (Gene Therapy and Regulation (2010) 5 (31-55) DOI: 10.1142/S1568558610000197) 校误:一个新的重组腺相关病毒(AAV)为基础的随机肽展示文库系统:感染缺陷的AAV1.9-3作为载体进化的一个新的去靶向平台(基因治疗和调控(2010)5 (31-55)DOI: 10.1142/S1568558610000197)

Gene therapy and regulation Pub Date : 2011-03-01 DOI: 10.1142/S156855861100026X

K. Adachi, H. Nakai

引用次数: 1

ADVANCES IN MOLECULAR THERAPY RESEARCH ON DYSTROPHIN-DEFICIENT MUSCULAR DYSTROPHY 肌营养不良蛋白缺乏的分子治疗研究进展

Gene therapy and regulation Pub Date : 2010-10-01 DOI: 10.1142/S1568558610000203

T. Okada, S. Takeda

{"title":"ADVANCES IN MOLECULAR THERAPY RESEARCH ON DYSTROPHIN-DEFICIENT MUSCULAR DYSTROPHY","authors":"T. Okada, S. Takeda","doi":"10.1142/S1568558610000203","DOIUrl":"https://doi.org/10.1142/S1568558610000203","url":null,"abstract":"Duchenne muscular dystrophy (DMD) is a lethal muscle disorder caused by mutations of the DMD gene, which encodes a 427-kDa spectrin-like cytoskeletal protein, dystrophin. Exon skipping induced by antisense oligonucleotides is a novel method to restore the reading frame of the mutated DMD gene and rescue dystrophin expression. We recently demonstrated that systemic delivery of antisense phosphorodiamidate morpholino oligonucleotides (PMOs) targeting exons 6 and 8 of the canine DMD gene efficiently recovered functional dystrophin at the sarcolemma of dystrophic dogs, and improved performance of the affected dogs without serious side effects. As a strategy to target hot spots of mutation in the DMD gene, we also tried exon 51-skipping using PMOs in mdx52 mice to convert an out-of-frame mutation into an in-frame mutation with restoration of dystrophin expression in various muscles and improvement of pathology and function. Progress in adeno-associated virus vector serotype 9 (AAV-9)-mediated DMD gene therapy has enabled the delivery of the therapeutic gene to the whole musculature, including cardiac muscle, while evoking minimal immunological reactions in mice, dogs, and non-human primates. Furthermore, DMD-derived patient-specific induced pluripotent stem (iPS) cells could be a potential source for cell therapy, although there are at present hurdles to be overcome. In the future, this technology could be used in combination with exon skipping or AAV-mediated gene therapy to achieve clinical benefits.","PeriodicalId":93646,"journal":{"name":"Gene therapy and regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S1568558610000203","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64015467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CLINICAL DEVELOPMENT OF AAV VECTORS aav载体的临床发展

Gene therapy and regulation Pub Date : 2010-10-01 DOI: 10.1142/S1568558610000215

B. Carter

引用次数: 0

GENE THERAPY FOR PARKINSON'S DISEASE: STRATEGIES FOR THE LOCAL PRODUCTION OF DOPAMINE 帕金森病的基因治疗:局部产生多巴胺的策略

Gene therapy and regulation Pub Date : 2010-10-01 DOI: 10.1142/S1568558610000173

S. Muramatsu, Sayaka Asari, K. Fujimoto, K. Ozawa, I. Nakano

{"title":"GENE THERAPY FOR PARKINSON'S DISEASE: STRATEGIES FOR THE LOCAL PRODUCTION OF DOPAMINE","authors":"S. Muramatsu, Sayaka Asari, K. Fujimoto, K. Ozawa, I. Nakano","doi":"10.1142/S1568558610000173","DOIUrl":"https://doi.org/10.1142/S1568558610000173","url":null,"abstract":"The cardinal motor symptoms of Parkinson's disease (PD) are associated with the profound depletion of dopamine in the striatum. The replacement of dopamine is the most straightforward strategy to improve motor performance in PD. Researchers have been developing gene therapy aimed at local production of dopamine via the introduction of dopamine-synthesizing enzyme genes into the putamen. Two phase I clinical studies have used recombinant adeno-associated virus (AAV) vectors to transfer the aromatic L-amino acid decarboxylase (AADC) gene into the putamen to restore efficient conversion of orally administered L-3,4-dihydroxyphenylalanine (L-dopa). The initial results of these studies have not only confirmed the safety of AAV vectors, but have also demonstrated the alleviation of motor symptoms associated with PD. Interestingly motor performance in the \"off\" medication state was improved after gene therapy, suggesting long-term modulation of dopaminergic signals in the striatal neurons was induced by gene transfer. Gene delivery of tyrosine hydroxylase (TH) and guanosine triphosphate cyclohydrolase I (GCH) in addition to AADC may help to avoid motor fluctuations associated with intermittent intake of L-dopa by continuously supplying dopamine in the putamen. A clinical study of such triple gene transfer is presently underway using equine infectious anemia virus (EIAV) vector.","PeriodicalId":93646,"journal":{"name":"Gene therapy and regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S1568558610000173","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64015406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

CLINICAL DEVELOPMENT OF A THIRD-GENERATION ONCOLYTIC HSV-1 (G47Δ) FOR MALIGNANT GLIOMA 第三代溶瘤hsv-1 (g47Δ)治疗恶性胶质瘤的临床进展

Gene therapy and regulation Pub Date : 2010-10-01 DOI: 10.1142/S1568558610000185

Y. Ino, T. Todo

{"title":"CLINICAL DEVELOPMENT OF A THIRD-GENERATION ONCOLYTIC HSV-1 (G47Δ) FOR MALIGNANT GLIOMA","authors":"Y. Ino, T. Todo","doi":"10.1142/S1568558610000185","DOIUrl":"https://doi.org/10.1142/S1568558610000185","url":null,"abstract":"Genetically engineered, conditionally replicating herpes simplex viruses type 1 (HSV-1) are promising therapeutic agents for cancer. We have developed a triple-mutated, third-generation oncolytic HSV-1, G47Δ, by introducing an additional genetic mutation to the viral genome of G207, a second generation HSV-1, used in clinical trials for malignant glioma in the United States. Preclinical studies demonstrated that G47Δ exhibited increased antitumor efficacy in various tumor models while preserving the safety of G207. Prior to the first-in-man clinical trial, G47Δ genome structure analysis, stability tests, and preclinical safety evaluation using HSV-1-susceptible A/J mice were performed. After development and optimization of manufacturing processes, clinical-grade G47Δ was produced at the GMP vector production facility of the University of Tokyo. Quality tests under GLP were completed for clinical products at 4 manufacturing steps. The first clinical trial of G47Δ is designed as an open labeled, single armed, phase I-II study for patients with recurrent glioblastoma. Patients with a single lesion, age 18 or older, and with Karnofsky Performance Scale (KPS) 70% or higher are enrolled. G47Δ is administered stereotactically into multiple sites of the tumor, twice within 14 days. The primary endpoint is to assess the safety of G47Δ, and the secondary endpoint is to assess the efficacy by tumor size and progression-free survival. After 3 years of contact with and review by regulatory authorities, the final governmental approval was obtained in May 2009, and the patient registration began in November 2009. In this paper, we also review the background of the clinical development of G47Δ.","PeriodicalId":93646,"journal":{"name":"Gene therapy and regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S1568558610000185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64015419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

RECENT PROGRESS AND FUTURE DIRECTIONS USING ENGINEERED T CELLS FOR THE TREATMENT OF CANCER 利用工程t细胞治疗癌症的最新进展和未来方向

Gene therapy and regulation Pub Date : 2010-10-01 DOI: 10.1142/S1568558610000161

N. Chinnasamy, R. Morgan

引用次数: 1

SMART ADENOVIRUS NANOCOMPLEXES FOR SYSTEMIC DELIVERY 用于系统递送的智能腺病毒纳米复合物

Gene therapy and regulation Pub Date : 2010-10-01 DOI: 10.1142/S1568558610000227

E. Kang, C. Yun

{"title":"SMART ADENOVIRUS NANOCOMPLEXES FOR SYSTEMIC DELIVERY","authors":"E. Kang, C. Yun","doi":"10.1142/S1568558610000227","DOIUrl":"https://doi.org/10.1142/S1568558610000227","url":null,"abstract":"A challenge to develop adenovirus (Ad)-mediated therapeutics has been issued to treat metastatic cancer via systemic administration. For effective gene therapeutics against primary and metastatic lesions, a systemically injectable tumor-targeting Ad vector system must be developed. Systemic delivery of Ad, however, is hampered by immune response against Ad, short half-life in the circulation, liver uptake, and low accumulation at target disease sites. Modification of the Ad surface allows Ad to circulate in the bloodstream for a longer time, to be not targeted to the liver, and to passively accumulate in tumor sites via enhanced permeation and retention effects. The addition of affinity tags results in active targeting and high efficacy. Strategies including addition of polymer complexes, chemical modifications, and targeting moieties have been applied to develop systemically injectable Ad gene therapeutic carriers. More versatile designs of Ad hybrid complexes have been developed with inorganic nanoparticles, polymers, and lipids, making smart nanomedicine possible. Integration of viral and nonviral nanomaterials can substantially synergize both fields, creating a new concept of gene therapeutics. Here, we describe the various Ad hybrid complex systems used to overcome the limited clinical applicability of conventional Ads and enable effective treatment of distant metastatic tumors via systemic injection.","PeriodicalId":93646,"journal":{"name":"Gene therapy and regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S1568558610000227","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64015526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

A NEW RECOMBINANT ADENO-ASSOCIATED VIRUS (AAV)-BASED RANDOM PEPTIDE DISPLAY LIBRARY SYSTEM: INFECTION-DEFECTIVE AAV1.9-3 AS A NOVEL DETARGETED PLATFORM FOR VECTOR EVOLUTION. 一种新的基于重组腺相关病毒（AAV）的随机多肽展示文库系统：感染缺陷AAV1.9-3作为载体进化的新型非靶向平台。

Gene therapy and regulation Pub Date : 2010-10-01 DOI: 10.1142/S1568558610000197

Kei Adachi, Hiroyuki Nakai

{"title":"A NEW RECOMBINANT ADENO-ASSOCIATED VIRUS (AAV)-BASED RANDOM PEPTIDE DISPLAY LIBRARY SYSTEM: INFECTION-DEFECTIVE AAV1.9-3 AS A NOVEL DETARGETED PLATFORM FOR VECTOR EVOLUTION.","authors":"Kei Adachi, Hiroyuki Nakai","doi":"10.1142/S1568558610000197","DOIUrl":"10.1142/S1568558610000197","url":null,"abstract":"<p><p>Directed evolution through genetic engineering of viral capsids followed by selection has emerged as a powerful means to create novel recombinant adeno-associated virus (rAAV) vectors with desired tropism and enhanced properties. One of the most effective approaches uses rAAV-based random peptide display libraries. Here we report a novel system based on an infection-defective rAAV1.9-3 as a platform for random peptide display, and show that biopanning of the libraries in vitro effectively identifies the peptides that restore and enhance rAAV transduction. rAAV1.9-3 has a genetically engineered AAV1 capsid with amino acids 445-568 being replaced with those of AAV9, and has been identified as a variant exhibiting significantly impaired infectivity and delayed blood clearance when infused into mice. In this study, we generated rAAV1.9-3 variant libraries in which 7- or 12-mer random peptides were expressed at the capsid amino acid position 590. Three rounds of positive selection for primary human dermal fibroblasts successfully identified new rAAV-peptide variants that transduce them more efficiently than the prototype rAAV2. Thus our study demonstrates that an infection-defective rAAV variant serves as a novel detargeted platform for random peptide display libraries. We also describe a brief review of recent progress in rAAV-based random peptide display library approaches.</p>","PeriodicalId":93646,"journal":{"name":"Gene therapy and regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3095953/pdf/nihms255949.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40102986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0