Gene Therapy
Chapters
« previous | page 2 of 3 pages | next »EIAV, CAEV and Other Lentivirus Vector Systems
John C. Olsen
Lentiviruses that infect non-primates make up a diverse collection of viruses. Although these viruses have some features in common with HIV and other primate viruses, differences in genome organization and viral gene function have made the successful derivation of vectors from non-primat...
Emerging Roles for the Retinoblastoma Gene Family
Jacqueline L. Vanderluit, Kerry L. Ferguson and Ruth S. Slack
Research on the retinoblastoma protein has grown from studying its role as a tumour suppressor in cancer to identifying it as a key regulator of the cell cycle G1/S check point and today to exploring its function in numerous cellular processes. The recent development of conditional knockout mice ...
Entry of Adenovirus into Cells
Prem Seth
With the advent of the electron microscope, it became possible to study the entry of adenoviruses into eukaryotic cells. Time course experiments of adenovirus uptake into the cells indicated a pathway of adenovirus entry which is similar to that followed by other ligands which enter the cells ...
Ethical Considerations in the Use of Lentiviral Vectors for Genetic Transfer
Ina Roy
This chapter will outline the various concerns which have been raised in scientific, bioethics, and lay communities about the use of lentiviral vectors for purposes of gene therapy. Many of these concerns are ranged around gene therapy itself; others are concerns particular to using this...
FIV Vector Systems
Sybille L. Sauter and Mehdi Gasmi
Why is feline immunodeficiency virus (FIV) such an appealing candidate for gene therapy vector development? Phylogenetic analysis suggests FIV is only distantly related to the primate lentiviruses, and despite repeated exposure, neither seroconversion nor other detectable evidence of hum...
HIV-1 Replication
Eric O. Freed
In general terms, the replication cycle of lentiviruses, including HIV-1, closely resembles that of other retroviruses.1 There are, however, a number of unique aspects of HIV replication; for example, the HIVs and SIVs target receptors and coreceptors distinct from those used ...
HIV-1 Vector Systems
Narasimhachar Srinivasakumar
Human immunodeficiency virus type 1 (HIV-1) based gene transfer systems are gaining in popularity due to their ability to transduce terminally differentiated and non-dividing cells. Oncoretroviral vectors based on Moloney murine leukemia virus (MoMLV), on the other hand, can only transdu...
HIV-2 and SIV Vector Systems
James R. Gilbert and Flossie Wong-Staal
Lentiviral vectors have received much attention in recent years due to their ability to efficiently transduce non-dividing cells. Of the lentiviruses HIV-2 and SIV offer several unique benefits as the basis for lentiviral vector design. HIV-1, HIV-2 and SIV remain the only known primate ...
Homologous Recombination Between Exogenous and Integrated Adenovirus
C. S. H. Young and Gregory J. Duigou
The recent dramatic increase in the use of adenovirus as a transduction vector has led to a renewed interest in all phases of its life cycle. Among the issues that have received increased attention are those concerning the genetic integrity of the viral genome after infection into either...
Host Immune Responses to Recombinant Adenoviral Vectors
Johanne M. Kaplan
Recombinant adenoviruses (Ad) are versatile gene delivery vectors capable of infecting a broad range of cell types without a requirement for cell division. They are being developed for a variety of clinical applications such as correction of inherited disorders, cancer gene therapy an...
IAP–Based Gene Therapy for Neurodegenerative Disorders
Stephen J. Crocker, Daigen Xu, Charlie S.Thompson, Peter Liston, and George S. Robertson
Neurodegenerative diseases are steadily becoming more prominent as human lifeexpectancy increases. Gene therapy holds tremendous promise for the long term treatment of neurodegenerative disorders. The potential successes of gene therapy as a clinically useful therapeutic will be determin...
Implications of the Innate Immune System for Adenovirus-Mediated Gene Transfer
Kazuhisa Otake and Bruce C. Trapnell
Adenovirus is one of the most well-studied viruses, partly due to its use as a model of eukaryotic gene expression and partly due to efforts to develop a vaccine against outbreaks of adenovirus infection. The potential use of adenovirus for in vivo gene therapy has renewed interest in...
Imprinted Genes and Human Disease: An Evolutionary Perspective
Francisco Ubeda and Jon F. Wilkins
Imprinted genes have been associated with a wide range of diseases. Many of these diseases have symptoms that can be understood in the context of the evolutionary forces that favored imprinted expression at these loci. Modulation of perinatal growth and resource acquisition has played a central role...
Introduction to Retroviruses and Retroviral Vectors
Gary L. Buchschacher, Jr.
As various viral vector systems for gene transfer are developed, interest in using such systems in applied settings continues to grow. This Chapter is designed to provide background information for readers interested in learning about lentiviral vector systems for gene transfer applicati...
New Insights Into Transcriptional Regulation by RB: One Size No Longer Fits All
Peggy J. Farnham
The retinoblastoma (Rb) protein is a key regulator of cell proliferation, differentiation, and tumorigenesis. Initial studies of Rb revealed that it binds to, and decreases the activity of, the E2F family of transcription factors. Over the last decade, the mechanisms by which Rb regulates E2F act...
Opportunities for p53 Tumor Suppressor Gene Therapy in Ovarian and
Loretta L. Nielsen, Mark Pegram, Beth Karlan, John Elkas, and Jo Ann Horowitz
Schering–Plough Research Institute is currently sponsoring phase I/II clinical trials of adenovirus–mediated p53 gene therapy for cancer in several countries. The drug used in these clinical trials (Ad p53; ACN53; SCH58500) consists of a replication–deficient, type 5 adeno...
Organization of the Adenoviral Genome
Jane Flint
The DNA genomes of adenoviruses have been the objects of intense scrutiny since the first representative of this virus family was isolated in the winter of 1953–54.1 Both the oncogenicity of human serotypes, first recognized in 1962,2 and the expression of v...
pRb in the Differentiation of Normal and Neoplastic Cells
Deborah Pajalunga, Grazia Camarda and Marco Crescenzi
This chapter deals with the role played by the retinoblastoma protein (pRb) in a variety of differentiation processes. After broadly reviewing the current knowledge on this issue, it points at two common themes. The first is the exclusive involvement of pRb in the final maturation stages of each ...
Prospects for Gene Therapy Using HIV-Based Vectors
Jiing-Kuan Yee and John A. Zaia
Recombinant vectors derived from murine leukemia virus (MLV) have been widely used to introduce genes in human gene therapy clinical trials and have shown the potential for medical applications and the promise of significantly improving medical therapies. Yet, the demonstrated limitation...
Rb and Cellular Differentiation
Lucia Latella and Pier Lorenzo Puri*
The pivotal role of the Retinoblastoma gene product p110 (pRb) in cellular differentiation has been postulated since the identification of pRb as a target of oncogenic events.1-3 The demonstration of the essential role of pRb during terminal differentiation of many tissues appeared evident along ...
RB as Positive Transcriptional Regulator During Epithelial Differentiation
Chantal E. Cremisi and Linda L. Pritchard
RB plays an essential role in epithelial cell differentiation and viability, these two properties being totally linked and independent of p53. To exert these functions, RB acts as a positive transcriptional coregulator, being recruited to the native gene promoters by sequence-specific transcripti...
Regulation of DNA Replication by the Retinoblastoma Tumor Suppressor Protein
Erik S. Knudsen and Steven P. Angus
The retinoblastoma gene product (RB) plays a critical role in the inhibition of cancer. This prototypical tumor suppressor was identified based on bi-alleleic inactiviation in the pediatric tumor retinoblastoma. Subsequently, it has become clear that multiple pathways lead to the functional inact...
Regulation of E2F-Responsive Genes through Histone Modifications
Estelle Nicolas, Laetitia Daury and Didier Trouche
The retinoblastoma protein Rb, when targeted to E2F-responsive promoters through a direct interaction with E2F proteins, actively represses transcription. This property is shared by the two Rb-related proteins, p107 and p130. Active transcriptional repression by Rb is important for the proper con...
Regulation of Rb Function by Noncyclin Dependent Kinases
Jaya Padmanabhan and Srikumar P. Chellappan
Inactivation of the retinoblastoma tumor suppressor protein, Rb, is necessary for the normal progression of the mammalian cell cycle.1 Studies over the past fifteen years have shown that Rb protein is inactivated by kinases associated with cyclins, especially cyclins D and E, which facilitate the...
Role of Endoprotease in Adenovirus Infection
Joseph Weber
With the possible exception of very simple viruses, most viruses appear to encode at least one virus-specific endopeptidase. In addition to facilitating the orchestrated fragmentation of polyproteins of RNA viruses, these proteolytic enzymes may also be involved with the suppression o...
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