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US7968087: Gene delivery vectors provided with a tissue tropism for smooth muscle cells, and/or endothelial cells

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Filing Information

Inventor(s) Ronald Vogels · Menzo J. E. Havenga · Abraham Bout ·
Assignee(s) Crucell Holland B.V. ·
Attorney/Agent(s) TraskBritt, P.C. ·
Primary Examiner Shin-Lin Chen ·
Application Number US12455086
Filing date 05/28/2009
Issue date 06/28/2011
Prior Publication Data
Predicted expiration date 07/07/2019
U.S. Classifications 424/932.1  · 435/455  · 435/320.1  · 536/237.2  · 424/932  ·
International Classifications A01N6300  · A61K4800  · C07H2104  · C12N1500  · C12N1563  ·
Kind CodeB2
Related U.S. Application DataCROSS-REFERENCE TO RELATED APPLICATION
This application is a continuation of U.S. patent application Ser. No. 11/018,669, filed Dec. 20, 2004, now abandoned, which application is a continuation of U.S. patent application Ser. No. 09/444,284, filed Nov. 19, 1999, now U.S. Pat. No. 6,929,946, issued Aug. 16, 2005, which is a continuation-in-part of application Ser. No. 09/348,354, filed Jul. 7, 1999, abandoned, the contents of both of which are incorporated by this reference.
Foreign Priority EP98203921 - 11/20/1998 ·
5 Claims, 23 Drawings


Abstract

A gene delivery vehicle having been provided with at least a tissue tropism for cells selected from the group of smooth muscle cells, endothelial cells, and/or liver cells. The tissue tropism is generally provided by a virus capsid, such as one comprising protein fragments from at least two different viruses, such as two different adenoviruses, including adenovirus of subgroup C or subgroup B (for example, adenovirus 16). The protein fragments can comprise a tissue tropism-determining fragment of a fiber protein derived from a subgroup B adenovirus. Also, cells for producing such gene delivery vehicles and pharmaceutical compositions containing these gene delivery vehicles are provided. Further, a method is disclosed for delivering nucleic acid to cells such as smooth muscle cells and/or endothelial cells which involves administering to the cells an adenovirus capsid having proteins from at least two different adenoviruses and wherein at least a tissue tropism-determining fragment of a fiber protein is derived from a subgroup B adenovirus. Particular constructs are also disclosed.

Independent Claims | See all claims (5)

  1. 1. A method of delivering a non-adenoviral nucleic acid to a smooth muscle cell, the method comprising: delivering the non-adenoviral nucleic acid to said smooth muscle cell by infecting said smooth muscle cell with a recombinant adenovirus comprising: a fiber of adenovirus 11, 16, 35, or 51; and a non-adenoviral nucleic acid encoding a non-adenoviral polypeptide.
  2. 5. A method of delivering a non-adenoviral nucleic acid to a smooth muscle cell, the method comprising: infecting the smooth muscle cell with an adenovirus comprising: a fiber of adenovirus 16; and a non-adenoviral nucleic acid encoding a non-adenoviral polypeptide, wherein the non-adenoviral polypeptide is selected from the group consisting of an apolipoprotein, a nitric oxide synthase, a herpes simplex virus thymidine kinase, an interleukin-3, an interleukin-1α, an anti-angiogenesis protein, angiostatin, an anti-proliferation protein, a smooth muscle cell anti-migration protein, a vascular endothelial growth factor, a basic fibroblast growth factor, a hypoxia inducible factor 1α, and a Plasminogen Activator Inhibitor, wherein the adenovirus further has an adenoviral genome of an adenovirus of serotype 5, wherein the adenoviral genome is modified by a deletion of at least an E1 gene, so as to deliver said non-adenoviral nucleic acid to the smooth muscle cell.

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