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Gene Therapy

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Ad& - p53 Clinical Trial in Patients with Squamous Cell Carcinoma

Gary L. Clayman, Douglas K. Frank, and Patricia A. Bruso

Our laboratory has been involved in the investigation of wild type p53 gene transfer for the selective induction of apoptosis in human upper aerodigestive tract squamous cell carcinoma of the head and neck (SCCHN). Transient overexpression of the wild type p53 gene in various malignan...

AdCFTR for Cystic Fibrosis

Samuel C. Wadsworth

Cystic fibrosis (CF) is a recessive, monogenic, lethal disorder caused by defects in a protein termed the cystic fibrosis transmembrane conductance regulator (CFTR) .1,2 Approximately 60,000 individuals are affected worldwide. CFTR is an ion channel that functions to allow ...

Adenoviral Gene Therapy for Malignant Pleural Mesothelioma

Daniel H. Sterman, Larry R. Kaiser, and Steven M. Albelda

Malignant mesothelioma is a primary neoplasm of the mesothelial lining of the pleural (80%) or peritoneal cavities (19.5%). It has been linked conclusively to prior exposure to asbestos and may also be associated with certain genetic predispositions and past viral ex...

Adenoviral Vectors for Cancer Gene Therapy

Prem Seth, Yu Katayose, and Amol N.S. Rakkar

Cancer can be considered a "genetic" disorder, and thus a legitimate target for gene therapy, in as much as it arises as a result of a stepwise accumulation of genetic defects in a clone of cells. In the last decade or so, several epigenetic and genetic events have been characterized ...

Adenoviral Vectors for Cardiovascular Diseases

Noel M. Caplice, Timothy O'Brien, and Robert D. Simari

Cardiovascular diseases affect over 60 million people in the United States, and resulted in over 150 billion dollars in expenses in 1996 (American Heart Association, 1997). As such, the potential for clinical benefits from cardiovascular gene transfer is great and the targets for ther...

Adenoviral Vectors for Liver Cancer—Clinical Trials

Ragai R. Mitry, Catherine E. Sarraf, Nagy A. Habib

Malignant tumors of the liver are among the commonest cancers in the world, with an estimated annual global incidence of 1,000,000 cases per year.1 This includes primary tumors such as hepatocellular carcinoma (HCC) and metastases in the liver from various primary sites, for e...

Adenoviral Vectors for the Manipulation of Human Hematolymphoid Cells: Purging and Other Applications

Timothy C. Meeker, Joanne M. Wroblewski and Prem Seth

The human bone marrow produces a complex array of specialized cells designed to function in a myriad of ways. The pluripotent hematopoietic stem cell (HSC) gives rise to committed progenitors for the myeloid and lymphoid lineages. Myeloid progenitors ultimately give rise to granulocyt...

Adenoviral Vectors for Vaccines

Bernard Klonjkowski, Caroline Denesvre, and Marc Eloit

Several viruses can be used for the development of vectors for vaccination purposes. The human adenovirus type 2 (Ad2) and 5 (Ad5) have been used most extensively because of the greater understanding of their genome and interaction with the host cells. Nevertheless, for vaccination purpo...

Adenovirus Assembly

Susanne I. Schmid and Patrick Hearing

The assembly of adenovirus particles proceeds through an ordered series of assembly events (reviewed in ref. 1). The assembly of the virus particles has been probed using viral temperature-conditional mutants blocked at different stages of assembly at the restrictive temperature and by p...

Adenovirus Capsid Proteins

John J. Rux and Roger M. Burnett

Since Rowe et al1 first isolated adenovirus from human adenoid cells, more than 100 different species have been identified from various mammals. The family is characterized by the distinctive architecture of the virion, or virus particle, which is formed from a well defined...

Adenovirus DNA Replication

Muralidhara Ramachandra and R. Padmanabhan

After adenovirus (Ad) enters the cell by receptor–mediated endocytosis, the viral DNA is uncoated and transported to the nucleus. Beginning at 6–8 hours post–infection, DNA is efficiently replicated, generating high amounts of progeny molecules (105–10...

Adenovirus Late Gene Expression

Julie Boyer and Gary Ketner

The late phase of an adenovirus infection begins with the onset of viral DNA replication. During the late phase, protein synthesis in adenovirus-infected cells is dominated by the production of large quantities of the adenovirus capsid proteins and of a few non-structural proteins requir...

Adenovirus Transformation and Tumorigenicity

Robert P. Ricciardi

In natural infection of humans, adenoviruses generally enter differentiated, quiescent epithelial cells. For successful propagation of virus to occur, these infected cells need to be growth stimulated. This function is performed by the concerted actions of the viral E1A and E1B gene prod...

Adenovirus Vectors for Therapeutic Gene Transfer to Skeletal Muscles

Josephine Nalbantoglu, Basil J. Petrof, Rénald Gilbert, and George Karpati

Duchenne's muscular dystrophy (DMD) and the less severe Becker muscular dystrophy (BMD) result from mutations in the dystrophin gene on chromosome Xp21.1 DMD, which afflicts approximately 1 in 3,500 male newborns, is fatal by the third decade of life in most patients, usually ...

Adenovirus–Host Interactions to Subvert the Host Immune System

William S. M. Wold and Ann E. Tollefson

Viruses have evolved ingenious mechanisms to evade the host antiviral response. The first to be recognized is antigenic variation, which allows viruses to escape preexisting antibodies, and is exemplified by influenza virus epidemics that occasionally sweep across the world. Essentially ...

Adenovirus-AAV Combination Strategies for Gene Therapy

Krishna J. Fisher

Among the repertoire of eukaryotic viruses that have been genetically engineered for targeting therapeutic genes to somatic cells, adenovirus has captured considerable attention since the early 1990s. And, while much can be said about the strengths and weaknesses of adenovirus vectors fo...

Adenovirus-Induced Pathogenesis

Harold S. Ginsberg

With the discovery of antibiotics during World War II, the use of tissue culture soon became relatively easy after the war had ended. These findings led to the discovery of many new viruses. One of these, as described in chapter 1, was adenoviruses, in 19531 and 1954.2...

Adenovirus-Mediated Gene Transfer: Applications in Lipoprotein Research

Silvia Santamarina-Fojo and Marcelo J.A. Amar

In the last decade adenovirus–mediated in vivo gene transfer has been effectively utilized to enhance our understanding of the role that different apolipoproteins, enzymes, receptors and transfer proteins play in lipoprotein metabolism, as well as to identify potential candid...

Correction of Serum Protein Deficiencies with Recombinant Adenoviral

James N. Higginbotham and Prem Seth

There are numerous inherited and acquired serum protein deficiencies that cause moderate to severe and even life threatening diseases in people. Some of the diseases include a1–antitrypsin deficiency, hemophilias A and B, diabetes mellitus, and ...

Determinants for Lentiviral Infection of Non-Dividing Cells

Marie A. Vodicka

Lentiviruses share the common characteristic of infecting non-dividing target cells, distinguishing them from the oncogenic retroviruses which only productively infect dividing cells. The search for determinants for infection of non-dividing cells has produced a number of candidates. Fro...

Development of Adeniviral Vectors for Gene Therapy

Dai Katayose, Prem Seth

In recent years adenoviruses have been extensively used as vectors to deliver foreign genome into mammalian cells (reviewed in refs. 1-5). Adenoviruses have certain features, which make them attractive vectors for gene transfer to target cells. Some of these properties include their abil...

Development of an E1B, 55 kDa Gene–Deleted, Selectively Replicating

David H. Kirn

The vast majority of human cancers are incurable once metastatic. Chemotherapy and radiotherapy can induce tumor growth inhibition or regression in some cases, but solid tumor progression and resistance to these standard therapeutic modalities inevitably develops. Therefore, new agent...

Discovery and Classification of Adenoviruses

Harold S. Ginsberg

In 1953, Wallace Rowe was then a postdoctoral fellow at the National Institutes of Health with Robert Huebner; they were working, with their colleagues, to isolate the "virus of the common cold." Toward this goal, Dr. Rowe was using explants of adenoids and tonsils grown in cell cultu...

Diverse Regulatory Functions of the E2F Family of Transcription Factors

Fred Dick and Nick Dyson

E2F activity is largely controlled by cell cycle dependent phosphorylation of the Retino blastoma family of proteins (eg. pRB). Regulation of E2F transcription factors by RB-family proteins is crucial to the regulation of cell cycle entry. In addition to masking E2F activation of transcription, p...

Early Gene Expression

Philip E. Branton

The major targets of human adenoviruses are terminally differentiated epithelial cells of the upper respiratory tract, gut and eye. Once the virus has entered the cell and its DNA uncoated appropriately, progression of the infectious cycle depends on the ability of the virus to solve sev...


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