Gene therapy and regulation最新文献

{"title":"3D CELL BIOPRINTING FOR REGENERATIVE MEDICINE RESEARCH AND THERAPIES","authors":"C. Khatiwala, R. Law, B. Shepherd, S. Dorfman, M. Csete","doi":"10.1142/S1568558611000301","DOIUrl":"https://doi.org/10.1142/S1568558611000301","url":null,"abstract":"Tissue engineering tools and technologies are critical for regenerative medicine and the translational research supporting development of cell-based therapies. 3D cell bioprinting is a relatively new engineering tool being used to design 3D cell constructs (rather than cell suspensions) for transplantation therapies. In this review, we describe a broad range of printing technologies now being used to deliver cells and biomaterials in preclinical studies. We focus on 3D cell bioprinting, in which the building blocks (or 'bioink') used in printing process are three-dimensional cell structures, that are placed by the bioprinter into precise architectures to generate small tissues or organs. 3D cell bioprinting is a flexible research tool for basic and translational stem cell biology.","PeriodicalId":93646,"journal":{"name":"Gene therapy and regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S1568558611000301","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64015979","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}

{"title":"NUCLEAR REPROGRAMMING AND THE CURRENT CHALLENGES IN ADVANCING PERSONALIZED PLURIPOTENT STEM CELL-BASED THERAPIES","authors":"J. Byrne","doi":"10.1142/S1568558612300028","DOIUrl":"https://doi.org/10.1142/S1568558612300028","url":null,"abstract":"John Gurdon's discovery that somatic cells could be reprogrammed back into a pluripotent state has immense implications across multiple different fields, including the future potential for autologous cellular therapies. This review briefly examines the history of nuclear reprogramming, from Gurdon's original work in amphibia, through the generation of oocyte-reprogrammed pluripotent stem cells in the non-human primate and recent defined factor-based reprogramming approaches to generate human induced pluripotent stem (iPS) cells. This review also examines the five principle challenges towards safely advancing pluripotent stem cell derivatives into personalized human therapeutics, specifically: genetic stability, epigenetic memory, post-transplantation efficacy, post-transplantation safety and feasibility, and additionally discusses various hypotheses that may play a role in resolving the aforementioned challenges. Focused on iPS cells and derivatives, these hypotheses essentially deal with aging research, ...","PeriodicalId":93646,"journal":{"name":"Gene therapy and regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S1568558612300028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64015542","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}

{"title":"EDITORIAL — NOBEL PRIZE HIGHLIGHT: SOMATIC CELL REPROGRAMMING AND THE CURRENT CLINICAL GRADE CHALLENGE","authors":"R. Bertolotti","doi":"10.1142/S1568558612300016","DOIUrl":"https://doi.org/10.1142/S1568558612300016","url":null,"abstract":"","PeriodicalId":93646,"journal":{"name":"Gene therapy and regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S1568558612300016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64015989","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}

{"title":"S/MAR VECTORS — ALTERNATIVE EXPRESSION SYSTEMS FOR GENE THERAPY?","authors":"C. Hagedorn, H. Lipps","doi":"10.1142/S156855861230003X","DOIUrl":"https://doi.org/10.1142/S156855861230003X","url":null,"abstract":"Due to the lack of natural occurring plasmids in higher eukaryotes, most vectors currently used for the modification of mammalian cells and organisms are based on modified viruses. But the use of these virus-based vectors still has severe safety risks and therefore considerable efforts are made to design alternative vector systems, whose function are based on chromosomal elements and which behave as an autonomous unit in the cell. The construction of episomal vectors was hindered by our limited knowledge of the epigenetic regulation of replication in higher eukaryotes. However, in the late 1990, a prototype non-viral episomal vector was constructed which replicates autonomously in all mammalian cells and is mitotically stable in the absence of selection. Its function relies on an expression unit linked to a scaffold/matrix-attached region (S/MAR). In this short review, we describe the rational of its construction and functioning. The prototype vector was improved within the past years with respect to establishment and expression efficiency and has now been tested for various preclinical applications. Eventually, S/MAR-based vectors will be improved to such a stage that they can provide a safe alternative to viral vectors to be used in gene therapy.","PeriodicalId":93646,"journal":{"name":"Gene therapy and regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S156855861230003X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64015553","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}

{"title":"MURINE PGK PROMOTER IN A LENTIVIRAL VECTOR IN CANINE LEUKOCYTE ADHESION DEFICIENCY AND IN HUMAN LAD-1 CD34+ CELLS IN NSG MICE","authors":"M. Hunter, U. Choi, L. Tuschong, Huifen Zhao, S. Koontz, V. Kapoor, D. Persons, H. Malech, D. Hickstein","doi":"10.1142/S156855861250001X","DOIUrl":"https://doi.org/10.1142/S156855861250001X","url":null,"abstract":"The safety of lentiviral (LV) vectors for gene therapy of genetic hematopoietic diseases would be considerably enhanced by the identification of a non-viral promoter capable of driving therapeutic levels of transgene expression in the target cell. Here, we tested the efficacy of the murine phosphoglycerate kinase (mPgk) promoter in a self-inactivating (SIN) LV vector to express canine CD18 in animals with canine leukocyte adhesion deficiency (CLAD) and in human LAD-1 CD34+ cells in NSG mice. Despite high transduction levels and high levels of CD18 expression per cell in CLAD CD34+ cells in vitro using the mPgk vector to drive canine CD18 expression, only two of five CLAD animals treated with ex vivo gene therapy achieved therapeutic levels of CD18+ neutrophils in vivo. Similarly, despite high transduction efficiency and high levels of CD18 expression in human LAD-1 CD34+ cells in vitro, the mPgk-hCD18 promoter resulted in a low percentage of CD45+/CD18+ cells and low levels of CD18 expression per neutrophil, when the transduced cells were transplanted into NSG mice. In contrast, human LAD-1 CD34+ cells transduced with a LV vector containing the viral MND promoter (MND-hCD18) and injected into NSG mice displayed a high percentage of CD45+/CD18+ cells and high levels of CD18 expression per neutrophil. These studies demonstrated that the mPgk promoter does not direct sufficient CD18 expression in neutrophils to replace a viral promoter for gene therapy of children with LAD-1.","PeriodicalId":93646,"journal":{"name":"Gene therapy and regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S156855861250001X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64015625","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}

{"title":"CORRIGENDUM TO \"SMART ADENOVIRUS NANOCOMPLEXES FOR SYSTEMIC DELIVERY\"","authors":"E. Kang, C. Yun","doi":"10.1142/S1568558611000271","DOIUrl":"https://doi.org/10.1142/S1568558611000271","url":null,"abstract":"","PeriodicalId":93646,"journal":{"name":"Gene therapy and regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S1568558611000271","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64015207","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}

{"title":"FULLY-PLURIPOTENT iPS CELLS: MOUSE TETRAPLOID COMPLEMENTATION, ETHICAL HUMAN ES-LIKE CELLS AND REPRODUCTIVE CLONING BAN","authors":"R. Bertolotti","doi":"10.1142/S1568558610000148","DOIUrl":"https://doi.org/10.1142/S1568558610000148","url":null,"abstract":"Full pluripotency of mouse induced pluripotent stem (iPS) cells was recently demonstrated using the tetraploid blastocyst complementation assay, thereby establishing transient transgenic expression of the \"four Yamanaka transcription factors\" as a bona fide reprogramming technique. Such a genesis of fertile adult \"iPS\" mice could revive the roguish temptation of banned human reproductive cloning currently doomed by the failure of human cell reprogramming by somatic cell nuclear transfer (SCNT). This major concern deals with a potential use of human iPS cells and contrasts with the fact that these cells stand as breakthrough ethical substitutes for current allogeneic human embryonic stem (ES) cells and planned patient-specific SCNT-ES cells. Indeed, unlike ES cells, iPS cells are generated without the need of an oocyte or a blastocyst and are therefore free of the human oocyte scarcity and embryo destruction problems. For patient-specific iPS cells, safety issues are thus the very limitation to the initiation of their bench-to-bedside translation. Full pluripotency is the first concern since it is the most stringent proof of an unbiased epigenetic reprogramming. Importantly, mouse tetraploid-complementing iPS cells have been shown to be few among the former deemed bona fide iPS cells and are thus expected to be instrumental in the identification of potential reprogramming caveats and of critical markers of the fully-pluripotent state. In this respect, hot-off-the-press data show that full pluripotency is correlated to the activity of the imprinted Dlk1-Dio3 multigenic region which is frequently aberrantly silenced in iPS cells. The stringency of the tetraploid complemention assay by mouse iPS cells is thus expected to translate soon into optimized protocols for the genesis/identification of fully-pluripotent human iPS cells. Such a full pluripotency is discussed in light of transgene-free reprogramming protocols aimed a clearing the second safety concern of iPS cell genesis: oncogenic hazards resulting from random integration of reprogramming transgenes into target-cell chromosomal DNA. In this respect, iPS cell genesis being the result of a transient gene therapy mechanism, the transient epigenetic gene therapy arm of our proposed universal stem cell gene therepy platform is presented together with concurrent approaches mediated by protein transduction, mRNA transfection and small molecules.","PeriodicalId":93646,"journal":{"name":"Gene therapy and regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S1568558610000148","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64015305","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}

{"title":"DROP-ON-DEMAND INKJET BIOPRINTING: A PRIMER ∗","authors":"Kyle W. Binder, A.J. Allen, J. Yoo, A. Atala","doi":"10.1142/S1568558611000258","DOIUrl":"https://doi.org/10.1142/S1568558611000258","url":null,"abstract":"Engineering complex biological structures for regenerative medicine, in vitro tissue analysis, and pharmaceutical testing require new fabrication techniques that can place specific cells in specific target locations. Conventional cell seeding methods cannot achieve this level of spatial resolution. Biofabrication is a rapidly advancing field that uses a variety of delivery mechanisms to achieve the spatial resolution necessary to place cells, biomaterials, and bioactive macromolecules in specific target locations. One new technique within this field is bioprinting, which uses drop-on-demand delivery mechanisms to fabricate biological structures. This review focuses on drop-on-demand inkjet bioprinting and provides a primer for researchers seeking to enter the field.","PeriodicalId":93646,"journal":{"name":"Gene therapy and regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S1568558611000258","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64015077","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}

{"title":"NEW RECOMBINANT ADENO-ASSOCIATED VIRUS (rAAV)-BASED THERAPEUTICS REACH PIVOTAL PHASE 2 CLINICAL TRIALS","authors":"C. Mueller, S. Kaushal, M. Humphries, T. Flotte","doi":"10.1142/S1568558611000295","DOIUrl":"https://doi.org/10.1142/S1568558611000295","url":null,"abstract":"This brief review summarizes the design of two phase 2 clinical trials of recombinant adeno-associated virus (rAAV)-based vector that are currently underway. These include a trial of a rAAV2-RPE65 vector for patients with Leber congenital amaurosis and a trial of a rAAV1-alpha-1-antitrypsin(AAT) vector delivered intramuscularly in patients with genetic emphysema due to AAT deficiency. In both cases, the current phase 2 trials were preceded by phase 1 trials indicating a good safety profile and persistent transgene expression.","PeriodicalId":93646,"journal":{"name":"Gene therapy and regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S1568558611000295","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64015968","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}

{"title":"EDITORIAL: \"THERMAL INKJET-MEDIATED TRANSFECTION AS AN ADDITIONAL FEATURE OF BIOPRINTING\"","authors":"R. Bertolotti","doi":"10.1142/S1568558611000283","DOIUrl":"https://doi.org/10.1142/S1568558611000283","url":null,"abstract":"","PeriodicalId":93646,"journal":{"name":"Gene therapy and regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S1568558611000283","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64015258","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}