Methods comprising apoptosis inhibitors for the generation of transgenic pigs

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Stem Cell Related Patent Number US6083911

Title:Arenavirus receptor and methods of use
Inventors:Campbell, Kevin P.; Iowa City, IA, USA
Henry, Michael; Iowa City, IA, USA
Yamada, Hiroki; Iowa City, IA, USA
Williamson, Roger; Iowa City, IA, USA
Cao, Wei; San Diego, CA, USA
Oldstone, Michael; La Jolla, CA, USA
Summary:Described herein are methods of treating and preventing arenavirus infections via the administration of a soluble alpha-dystroglycan to compete for cell surface binding receptors. The invention relates to a method of inhibiting the binding of an arenavirus to a cellular receptor such that a reagent is provided in soluble form which comprises an ?a-dystroglycan or a portion thereof, and which is characterized by the ability to bind to the arenavirus thereby inhibiting the binding of the arenavirus to the cellular receptor. Another embodiment of the invention relates to an embryonic stem cell line which is homozygous for a disrupted dystroglycan gene in which the disruption prevents the synthesis of functional dystroglycan in the cells. Therapeutic applications of such dystroglycan null embryonic stem cells include the production and identification of dystroglycan necessary for arenavirus infection. Strains of the arenavirus to which such therapeutic applications apply include Lymphocyte Choriomeningitis Virus, Lassa fever virus, Mobala, and Oliveros.
Abstract:Disclosed is a method for inhibiting the binding of an arenavirus to a cellular receptor. The method involves providing, in soluble form, a reagent comprising .alpha.-dystroglycan or a portion thereof, the reagent being characterized by the ability to bind to the arenavirus thereby inhibiting the binding of the arenavirus to the cellular receptor. The reagent is contacted with an arenavirus particle prior to infection of a cell by the arenavirus particle. Also disclosed are methods for treating an arenavirus infection in a patient and preventing an arenavirus infection in an individual at risk. These methods involve providing a therapeutic composition comprising .alpha.-dystroglycan or a portion thereof which is characterized by the ability to bind to arenaviruses, thereby inhibiting the binding of arenaviruses to a cellular receptor; and administering the composition to the patient or individual at risk. Arenaviruses to which the methods of the present invention apply include, without limitation, Lymphocyte Choriomeningitis Virus, Lassa fever virus, Mobala, and Oliveros. In another aspect, the disclosure relates to an embryonic stem cell line, and cells derived therefrom, which is homozygous for a disrupted dystroglycan gene, wherein the disruption prevents the synthesis of functional dystroglycan in the cells. Applications of the dystroglycan null embryonic stem cells include producing dystroglycan or a portion thereof in the cells and also for identifying portions of dystroglycan necessary for arenavirus infection. Also disclosed is a method for identifying antiviral compounds which interfere specifically with the binding of arenavirus and .alpha.-dystroglycan, comprising providing a binding assay system for the determination of binding of arenavirus and .alpha.-dystroglycan. The candidate antiviral compounds are introduced into the binding assay system and antiviral compounds which substantially inhibit binding of arenavirus to .alpha.-dystroglycan are identified.
US Patent Website:Click Here for Full Text of Patent
Title Number:US6083911
Application Number:US1998000208707
Date Filed:10/12/1998
Date Published:04/07/2000
Assignee:University of Iowa Research Foundation, Iowa City, IA, USA


 
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