Method of using adenoviral vectors with increased persistence in vivo
AssigneeGenVec, Inc.
InventorsThomas J. Wickham, Masaki Akiyama
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Abstract
The invention provides a method of expressing an exogenous nucleic acid in a mammal. The method comprises slowly releasing into the bloodstream a dose of replication-deficient or conditionally-replicating adenoviral vector having reduced ability to transduce mesothelial cells and hepatocytes. The normalized average bloodstream concentration of the adenovirus over 24 hours post-administration is at least about 1%. Alternatively, the normalized average bloodstream concentration over 24 hours post-administration is at least about 5-fold greater than the normalized average bloodstream concentration for an equivalent dose of a wild-type adenoviral vector. A method of destroying tumor cells in a mammal also is provided.
Claims59
A method of expressing an exogenous nucleic acid in a mammal, wherein the method comprises slowly releasing into the bloodstream of the mammal a dose of replication-deficient or conditionally-replicating adenoviral vector having a reduced ability to transduce mesothelial cells and hepatocytes compared to wild-type adenovirus and comprising an exogenous nucleic acid,
- wherein the normalized average bloodstream concentration of the replication-deficient or conditionally-replicating adenovirus over a time period of 24 hours post-administration, expressed as a percentage of the initial theoretical bloodstream concentration of a dose of adenoviral vector that is never cleared from the bloodstream, is at least about 1%,
- such that a host cell in the mammal is transduced and the exogenous nucleic acid is expressed.
A method of expressing an exogenous nucleic acid in a mammal, wherein the method comprises slowly delivering to the bloodstream of the mammal a dose of a replication-deficient or conditionally-replicating adenoviral vector having reduced ability to transduce mesothelial cells and hepatocytes compared to wild-type adenoviral vector and comprising an exogenous nucleic acid,
- wherein the normalized average bloodstream concentration of the replication-deficient or conditionally-replicating adenoviral vector over a time period of 24 hours post-administration is at least about 5-fold greater than the normalized average bloodstream concentration for an equivalent dose of a wild-type adenoviral vector.
A method of destroying tumor cells in a mammal, wherein the method comprises slowly delivering a dose of a replication-deficient or conditionally-replicating adenoviral vector to the bloodstream comprising (a) a nucleic acid sequence encoding a tumoricidal agent and (b) an adenoviral fiber protein which does not mediate adenoviral entry via a coxsackievirus and adenovirus receptor (CAR), such that the tumoricidal agent is produced and tumor cells in the mammal are destroyed.
Dependencies are inferred from the claim text.