Modified adenoviral fiber and target adenoviruses
AssigneeTransgene S.A.
InventorsValérie Legrand, Majid Mehtali, Pierre Boulanger
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Abstract
The invention relates to an adenovirus fiber modified by the mutation of one or more residues. The residues are directed towards the natural cell receptor in the three-dimensional structure of said adenovirus. The invention further relates to a DNA fragment, and expression vector, and a cell line expressing said fiber, and also concerns an adenovirus, the process for producing this type of adenovirus, and an infectable host cell, as well as their therapeutic application and a corresponding pharmaceutical composition.
Claims25
An adenovirus comprising a modified adenovirus fiber, the modification consisting of substituting one or more residues of a native fiber, wherein the substituted fiber residues are directed toward the natural cellular receptor recognized by the native adenovirus fiber, and are located between the CD loop and the β sheet I of said fiber, wherein said modification has the effect of reducing or abolishing the capacity of said adenovirus for binding to the natural cellular receptor, wherein said fiber is encoded by the genome of said adenovirus or provided in trans by a cell line, and wherein said adenovirus further comprises a ligand capable of recognizing a cell surface molecule different from the natural cellular receptor inserted into an adenoviral capsid protein other than said fiber.
An adenovirus comprising a modified adenovirus fiber, the modification consisting of substituting one or more residues of a native fiber, wherein said substituted fiber residues are directed toward the natural cellular receptor recognized by the native adenovirus fiber, and are located between the CD loop and the β sheet I of said fiber, wherein said modification has the effect of reducing or abolishing the capacity of said adenovirus for binding to the natural cellular receptor, and inserting a ligand, optionally connected through a spacer arm, at the C-terminus of said modified fiber, wherein the ligand is capable of recognizing a cell surface molecule different from the natural cellular receptor.
Dependencies are inferred from the claim text.