Compositions and methods for non-parenteral delivery of oligonucleotides

Abstract

The present invention relates to compositions and methods which enhance the local and systemic uptake and delivery of oligonucleotides and nucleic acids via non-parenteral routes of administration. Pharmaceutical compositions comprising oligonucleotides disclosed herein include, for systemic delivery, emulsion and microemulsion formulations for a variety of applications and oral dosage formulations. It has also surprisingly been discovered that oligonucleotides may be locally delivered to colonic sites by rectal enemas and suppositories in simple solutions, e.g., neat or in saline. Such pharmaceutical compositions of oligonucleotides may further include one or more penetration enhancers for the transport of oligonucleotides and other nucleic acids across mucosal membranes. The compositions and methods of the invention are utilized to effect the oral, buccal, rectal or vaginal administration of an antisense oligonucleotide to an animal in order to modulate the expression of a gene in the animal for investigative, therapeutic, palliative or prophylactic purposes.

1 - 15 . (Canceled).  
     
     
         16 . A method of treating an animal having an inflammatory bowel disorder comprising administering to said animal a therapeutically effective amount of an oligonucleotide formulation suitable for rectal delivery.  
     
     
         17 . The method of  claim 16 , wherein said animal is a human.  
     
     
         18 . The method of  claim 16 , wherein said inflammatory bowel disorder is ulcerative colitis.  
     
     
         19 . The method of  claim 16 , wherein said inflammatory bowel disorder is Crohn's disease or inflammatory bowel disease.  
     
     
         20 . The method of  claim 16 , wherein said oligonucleotide is an antisense oligonucleotide.  
     
     
         21 . The method of  claim 16 , wherein said formulation is an enema.  
     
     
         22 . The method of  claim 16 , wherein said formulation is a suppository.  
     
     
         23 . The method of  claim 20 , wherein said antisense oligonucleotide modulates expression of a cellular adhesion protein.  
     
     
         24 . The method of  claim 20 , wherein said antisense oligonucleotide modulates a rate of cellular proliferation or has biological activity against eukaryotic pathogens or retroviruses.  
     
     
         25 . The method of  claim 23 , wherein said cellular adhesion protein is ICAM-1.  
     
     
         26 . The method of  claim 25 , wherein said oligonucleotide has the sequence shown in SEQ ID NO: 1.