Chemistry: molecular biology and microbiology – Vector – per se
Patent
1994-06-17
1997-12-09
Ziska, Suzanne E.
Chemistry: molecular biology and microbiology
Vector, per se
4351723, 5303871, 536 231, 424 932, C12N 1800, C07K 1600, C07H 2102, A01N 6300
Patent
active
056959915
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a complex between virus the cell binding receptor of which has been inactivated and an antibody. The invention is applicable to situations where it is desireable to introduce viruses into selected mammalian cells for medicinal purposes.
Viruses enter mammalian cells following binding between a viral receptor and a chemical structure, or ligand, in the cell membrane. This initial binding is a first and necessary step leading to the entry of virus into the cell and the subsequent transcription of the viral genome and replication of the virus within the cell. Rather detailed knowledge about the structure and specificity of many viral raceptors is at hand. For example, in the case of influenza virus the specificity of the virus receptor is analogous to the specificity of antibodies against certain tumor antigens, in that the influenza virus hemagglutinin binds to NeuAc2-3Gal-R, which is present on the same structures as many human tumor associated antigens.
The main object of the present invention is to provide techniques enabling introduction of viruses into mammalian cells for providing desired biological action in such cells.
Another object of the invention is to enable virus vectors or infectious viruses to be directed to specific cells in a living animal body.
Yet another purpose is to provide techniques making it possible for viruses to selectively enter specific cells in a living animal body.
For these and other purposes the invention provides for a complex between a virus and an antigen-binding substance selected from antibodies, fragments of antibodies and antigen-binding peptides, the cell binding receptor of said virus being inactivated. Said substance has the ability to interact with a specific antigen on the surface of a mammalian cell which antigen is different from the cellular structure which would otherwise mediate binding of the virus to the cell surface. Furthermore, said substance has the ability to mediate entrance of a virus vector or infectious virus into the cell.
The substance can either be a monoclonal antibody or a fragment of a whole antibody.
The substance can be bound to the virus in different ways, such as by chemical conjugation, by bridging the substance to the virus by an immunochemical reagent, or by using a bifunctional substance binding to the virus as well as to a cellular antigen.
The substance may also be expressed on the virus surface envelope following cloning into the virus genome of gene(s) for whole antibodies or fragments thereof.
The inactivation of the viral cell receptor in accordance with the present invention can take place by chemical means, by a specific antibody or by gene technological manipulation of the viral genome. Thus, the gene for the viral cell receptor or parts thereof can be replaced with antibody genes.
The complex according to the present invention is intended for medicinal use. Thus, the complex can be used as a vector to introduce genes into cells or organs for specific therapeutical purposes. The complex may also be used to express viral antigens on the cell surface for such purposes or it can be used to cause an infection in cells carrying the substance against which the antibody is reactive.
BRIEF DESCRIPTION OF THE FIGURES
FIG. 1 shows a schematic drawing of replacing antibody conjugated to blocking antibody;
FIG. 2 shows a schematic drawing of replacing antibody conjugated to virus;
FIG. 3 shows a schematic drawing of viral gene for receptor replaced with antibody genes; and
FIG. 4 shows a schematic representation of the use of an antibody conjugate of the present invention.
By using an antibody which binds to a cellular membrane antigen which can be internalized into the cell, virus can bind to the cell via an antibody-antigen reaction and then penetrate into the cell and replicate causing a viral infection. Furthermore, since antigens are known which are more or less unique for certain types of cells, virus can be selectively directed to enter and infect specific cells in the body. Examples of such a
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Enerback Sven
Lindholm Leif
Stranneg.ang.rd Orjan
Got-A-Gene AB
Ziska Suzanne E.
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