Introgene B.v.

Vereniging Voor Christelijk Hoger Onderwijs, Wetenschappelijk Onderzoek En Patientenzorg

Vereniging Voor Christelijik Hoger Onderwijs, Wetenschappelijk Onderzoek En Patientenzorg

Victor Willem Van Beusechem

Domenico Valerio

Jan E Carette

Willem-Ronald Gerritsen

Jan Eduard Carette

Described is a replication-competent virus capable of replication and having lytic capacity in target cells. The virus comprises in the genome thereof, at least one DNA sequence coding for a silencing factor functional in reducing expression of a target gene in the target cells, operably linked to one or more expression control sequences, functional in the target cells. The use thereof in the preparation of a medicament and the use thereof in a method for lysing target cells expressing a virus inhibitory factor are also described.

Replication competent viruses capable of silencing virus inhibitory factor expression

Described is a replication competent recombinant virus, being capable to replicate and having lytic capacity in target cells, the said cell being hampered in the p53 dependent apoptosis pathway, the virus including in the genome thereof, the coding sequence of at least one restoring factor functional in restoring the p53 apoptosis pathway in the said target cells, operably linked to one or more expression control sequences, functional in the said target cells, as well as the use thereof in the preparation of a medicament, in particular for suppressing uncontrolled cell growth.

Viruses with enhanced lytic potency

A method is provided for genetically modifying primate bone marrow cells, comprising isolating bone marrow cells from a primate and, by means which enhance the local concentration of retroviral contacting the isolated bone marrow cells to cells that produce a recombinant amphotropic retrovirus with a genome based on a retroviral vector that contains the genetic information to be introduced into the bone marrow cells. Recombinant amphotropic retrovirus-producing cells, suitable for use in this method also are provided, as are genetically modified primate bone marrow cells with the capacity for regeneration in vivo.

Methods and compositions for genetically modifying primate bone marrow cells

A method of producing viral gene delivery vehicles which can be transferred to pre-selected cell types by using targeting conjugates. The gene delivery vehicles comprise: 1) the gene of interest; 2) a viral capsid or envelope carrying a member of a specific binding pair, the counterpart of which is not directly associated with the surface of the target cell. These vehicles can be made unable to bind to their natural receptor on the cell. The targeting conjugates are composed of the counterpart member of the specific binding pair linked to a targeting moiety which is a cell-type specific ligand. The number of the specific binding pair present on the viral vehicles can be, for example, an immunoglobulin binding moiety, biotin, avidin, or streptavidin. The outer membrane or capsid of the virus may contain a substance which mediates entrance of the gene delivery vehicle into the target cell. Due to the specificity of the ligand, the high affinity of the binding pair and to the inability of the gene delivery vehicle to be targeted when used alone, the universality of the method for gene delivery, together with its high cell type selectively can easily be achieved by the use of various adequate targeting conjugates.

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Amsterdam, Netherlands

Victor Willem Van Beusechem