Immunostimulatory nucleic acids

Abstract

The invention relates to immunostimulatory nucleic acid compositions and methods of using the compositions. The T-rich nucleic acids contain poly T sequences and/or have greater than 25% T nucleotide residues. The TG nucleic acids have TG dinucleotides. The C-rich nucleic acids have at least one poly-C region and/ore greater than 50% c nucleotides. These immunostimulatory nucleic acids function in a similar manner to nucleic acids containing CpG motifs. The invention also encompasses preferred CpG nucleic acids.

1 - 106 . (canceled)  
     
     
         107 . A therapeutic composition for the elicitation of a systemic, non-antigen specific immune response in a mammal comprising: 
 a. a liposome delivery vehicle; and    b. an isolated nucleic acid molecule selected from the group consisting of: 
 i. an oligonucleotide containing no CpG motifs; and  
 ii. an isolated nucleic acid vector without a gene insert, or a fragment thereof;  
   wherein said therapeutic composition elicits a systemic, non-antigen-specific immune response in said mammal.    
     
     
         108 . The composition of  claim 107 , wherein said liposome delivery vehicle comprises cationic liposomes.  
     
     
         109 . The composition of  claim 107 , further comprising a pharmaceutically acceptable excipient.  
     
     
         110 . The composition of  claim 109 , wherein said excipient comprises a non-ionic diluent.  
     
     
         111 . The composition of  claim 107 , wherein said oligonucleotide is at least 10 base pairs in length.  
     
     
         112 . The composition of  claim 111 , wherein said oligonucleotide is in the range of 10 to 100 base pairs in length.  
     
     
         113 . A method for eliciting a systemic, non-antigen specific immune response in a mammal, comprising administering to said mammal an amount of a composition effective to elicit said immune response, wherein said composition comprises: 
 a. a liposome delivery vehicle; and    b. an isolated nucleic acid molecule selected from the group consisting of: 
 i. an oligonucleotide containing no CpG motifs; and  
 ii. an isolated nucleic acid vector without a gene insert or a fragment thereof.  
   
     
     
         114 . The method of  claim 113 , wherein said liposome delivery vehicle comprises cationic liposomes.  
     
     
         115 . The method of  claim 113 , wherein said composition further comprises a pharmaceutically acceptable excipient.  
     
     
         116 . The method of  claim 115 , wherein said excipient comprises a non-ionic diluent.  
     
     
         117 . A pharmaceutical composition for inducing antigen non-specific innate immune activation in a subject comprising: 
 a. a nucleic acid delivery complex, and    b. an isolated oligonucleotide that is free of CpG dinucleotides,    wherein said composition induces an antigen non-specific innate immune activation in the subject.    
     
     
         118 . The composition of  claim 117 , wherein the immune activation comprises activation of NK cells.  
     
     
         119 . The composition of  claim 117 , wherein the immune activation comprises induction of IFN-gamma.  
     
     
         120 . The composition of  claim 117 , wherein the nucleic acid delivery complex comprises a sterol.  
     
     
         121 . The composition of  claim 120 , wherein the sterol is cholesterol.  
     
     
         122 . The composition of  claim 117 , wherein the nucleic acid delivery complex comprises a lipid.  
     
     
         123 . The composition of  claim 122 , wherein the lipid is a cationic lipid, virosome or liposome.  
     
     
         124 . The composition of  claim 117 , further comprising a pharmaceutically acceptable carrier.  
     
     
         125 . The composition of  claim 124 , wherein the carrier comprises a cellulose derivative, dextran or sorbitol.  
     
     
         126 . The composition of  claim 125 , wherein the cellulose derivative is sodium carboxymethyl cellulose.  
     
     
         127 . The composition of  claim 117 , wherein the oligonucleotide is at least 4 base pairs in length.  
     
     
         128 . The composition of  claim 127 , wherein the oligonucleotide has a length in the range of 6 to 100 nucleotides.  
     
     
         129 . The composition of  claim 117 , wherein the subject is a human.  
     
     
         130 . The composition of  claim 117 , wherein the antigen non-specific innate immune activation is systemic.  
     
     
         131 . The composition of  claim 117 , wherein the composition induces an antigen non-specific innate immune activation in the subject when administered by intraperitoneal or intravenous route.  
     
     
         132 . The composition of  claim 117 , wherein the oligonucleotide is a T-rich oligonucleotide or a TG oligonucleotide.  
     
     
         133 . The composition of  claim 117 , wherein the oligonucleotide has the sequence of SEQ ID NO:225, SEQ ID NO:282, or SEQ ID NO: 886.  
     
     
         134 . The composition of  claim 117 , wherein the composition induces an antigen non-specific innate immune activation in the subject when administered by parenteral route.  
     
     
         135 . A method for inducing an antigen non-specific innate immune activation in a subject, comprising administering to the subject an amount of a composition effective to induce the immune activation, wherein said composition comprises: 
 a. a nucleic acid delivery complex; and    b. an isolated oligonucleotide that is free of CpG dinucleotides.    
     
     
         136 . The method of  claim 135 , wherein the immune activation comprises activation of NK cells.  
     
     
         137 . The method of  claim 135 , wherein the immune activation comprises induction of IFN-gamma.  
     
     
         138 . The method of  claim 135 , wherein the nucleic acid delivery complex comprises a sterol.  
     
     
         139 . The method of  claim 138 , wherein the sterol is cholesterol.  
     
     
         140 . The method of  claim 135 , wherein the nucleic acid delivery complex comprises a lipid.  
     
     
         141 . The method of  claim 140 , wherein the lipid is a cationic lipid, virosome or liposome.  
     
     
         142 . The method of  claim 135 , further comprising a pharmaceutically acceptable carrier.  
     
     
         143 . The method of  claim 142 , wherein the carrier comprises a cellulose derivative, dextran or sorbitol.  
     
     
         144 . The method of  claim 143 , wherein the cellulose derivative is sodium carboxymethyl cellulose.  
     
     
         145 . The method of  claim 135 , wherein the subject is a human.  
     
     
         146 . The method of  claim 135 , wherein the antigen non-specific innate immune activation is systemic.  
     
     
         147 . The method of  claim 135 , wherein the composition is administered by intraperitoneal or intravenous route.  
     
     
         148 . The method of  claim 135 , wherein the oligonucleotide is a T-rich oligonucleotide or a TG oligonucleotide.  
     
     
         149 . The method of  claim 135 , wherein the oligonucleotide has the sequence of SEQ ID NO:225, SEQ ID NO:282, or SEQ ID NO: 886.  
     
     
         150 . The method of  claim 135 , wherein the composition is administered by parenteral route.