Inhibition of gene expression by delivery of polynucleotides to animal cells in vivo

Abstract

Described is a process for intravascular delivery of a polynucleotide to an extravascular cell of a mammal to inhibit gene expression. A polynucleotide containing sequence that is similar to a sequence in the gene to be expressed is made and inserted into a vessel in the mammal. The polynucleotide is delivered to a cell wherein expression of the gene is inhibited.

1 . An in vivo process for delivering a polynucleotide containing sequence similar to a sequence present in a gene that is expressed in an extravascular cell in an animal, comprising: 
 a) making the polynucleotide consisting of a double strand or partially double strand polynucleotide containing a sequence that is essentially complementary to a sequence in the gene;    b) injecting the polynucleotide, in a single injection, into an afferent or efferent vessel of a target tissue in which the extravascular cell is located in a sufficient volume to increase permeability of vessels in the tissue and deliver the polynucleotide to the extravascular cell.    
     
     
         2 . The process of  claim 1  wherein the polynucleotide inhibits expression of the gene.  
     
     
         3 . The process of  claim 2  wherein the gene consists of a viral gene.  
     
     
         4 . The process of  claim 3  wherein inhibiting the viral gene decreases viral toxicity.  
     
     
         5 . The process of  claim 3  wherein inhibiting the viral gene decreases viral replication.  
     
     
         6 . The process of  claim 3  wherein inhibiting the viral gene decreases viral virulence.  
     
     
         7 . The process of  claim 3  wherein the viral gene consists of a variola virus gene.  
     
     
         8 . The process of  claim 2  wherein inhibiting gene expression alters expression of an endogenous gene.  
     
     
         9 . The process of  claim 8  wherein inhibiting the endogenous gene alters a host response to a pathogen infection.  
     
     
         10 . The process of  claim 1  wherein the polynucleotide consists of a naked polynucleotide.  
     
     
         11 . The process of  claim 1  wherein the polynucleotide is associated with a compound.