Inhibitors of DNA Immunostimulatory Sequence Activity

A pharmaceutically useful compound for inhibiting immunostimulation by immunostimulatory sequence oligodeoxynucleotides comprising an oligonucleotide containing a hexamer region having the nucleotide sequence AAGGTT.

A pharmaceutically useful compound for inhibiting immunostimulation by immunostimulatory sequence oligodeoxynucleotides comprising an oligonucleotide containing a hexamer region having a nucleotide sequence consisting of AAGCTT.

A pharmaceutically useful compound for inhibiting immunostimulation by immunostimulatory sequence oligodeoxynucleotides comprising an oligonucleotide containing a hexamer region having a nucleotide sequence consisting of AGGGCT

A pharmaceutically useful compound for inhibiting immunostimulation by immunostimulatory sequence oligodeoxynucleotides comprising an oligonucleotide containing a hexamer region having a nucleotide sequence consisting of GAGGTT.

A method for inhibiting the immunostimulatory activity of ISS-ODN in contact with a population of vertebrate cells which includes lymphocytes or monocytes comprising contacting the population of vertebrate cells with an immunoinhibitory amount of an oligonucleotide containing a hexamer region having the nucleotide sequence 5′-Purine-Purine-[Y]-[Z]-Pyrmidine-Pyrimidine-3′ or 5′-Purine-Purine-[Y]-[Z]-Pyrimidine-poly(Pyrimidine)-3′, where Y is any naturally occurring or synthetic nucleotide except cytosine and Z is any naturally occurring or synthetic nucleotide;

• however, when Y is not guanosine or inosine, Z is guanosine or inosine;
• wherein a reduction in Th1 type immune responses measured in the population of vertebrate cells indicates that the desired inhibtion of ISS-ODN immunostimulatory activity has been achieved.

A method for prolonging gene expression in a recombinant expression vector believed to contain at least one ISS-ODN comprising contacting the recombinant expression vector with an immunoinhibitory amount of an oligonucleotide containing a hexamer region having the nucleotide sequence 5′-Purine-Purine-[Y]-[Z]-Pyrmidine-Pyrimidine-3′ or 5′-Purine-Purine-[Y]-[Z]-Pyrmidine-poly(Pyrimidine)-3′, where Y is any naturally occurring or synthetic nucleotide except cytosine and Z is any naturally occurring or synthetic nucleotide;

• however, when Y is not guanosine or inosine, Z is guanosine or inosine;
• wherein gene expression for a longer period of time than is obtained from the same recombinant expression vector in the absence of contact with the immunoinhibitory oligonucleotide indicates that the desired prolongation of gene expression has been achieved.

A method for reducing inflammation in a host in response to a microbial infection of the host comprising adminstering an immunoinhibitory amount of an oligonucleotide containing a hexamer region having the nucleotide sequence 5′-Purine-Purine-[Y]-[Z]-Pyrmidine-Pyrimidine-3′ or 5′-Purine-Purine-[Y]-[Z]-Pyrmidine-poly(Pyrimidine)-3′ to the host, where Y is any naturally occurring or synthetic nucleotide except cytosine and Z is any naturally occurring or synthetic nucleotide;

• however, when Y is not guanosine or inosine, Z is guanosine or inosine;
• wherein a reduction in Th1 type immune responses against the infectious microbe measured in the host or a reduction in other clinical signs of inflammation in the host indicates that the desired reduction in host inflammation has been achieved.

A method for modulating the immunostimulatory activity of an ISS-ODN in contact with a population of vertebrate cells which includes lymphocytes or monocytes comprising contacting the population of vertebrate cells with an immunoinhibitory amount of an oligonucleotide containing a hexamer region having the nucleotide sequence 5′-Purine-Purine-[Y]-[Z]-Pyrmidine-Pyrimidine-3′ or 5′-Purine-Purine-[Y]-[Z]-Pyrmidine-poly(Pyrimidine)-3′, where Y is any naturally occurring or synthetic nucleotide except cytosine and Z is any naturally occurring or synthetic nucleotide;

• however, when Y is not guanosine or inosine, Z is guanosine or inosine;
• wherein a reduction in Th1 type immune responses measured in the population of vertebrate cells indicates that the desired inhibtion of ISS-ODN immunostimulatory activity has been achieved.

A method for boosting a Th2 type immune response to an antigen comprising contacting a population of antigen stimulated vertebrate cells including lymphocytes with an immunostimulatory amount of an oligonucleotide containing a hexamer region having the nucleotide sequence 5′-Purine-Purine-[Y]-[Z]-Pyrmidine-Pyrimidine-3′ or 5′-Purine-Purine-[Y]-[Z]-Pyrmidine-poly(Pyrimidine)-3′, where Y is any naturally occurring or synthetic nucleotide except cytosine and Z is any naturally occurring or synthetic nucleotide;

• however, when Y is not guanosine or inosine, Z is guanosine or inosine;
• wherein wherein a reduction in Th1 type immune responses or increase in antigen stimulated IgG1 production measured in the population of vertebrate cells indicates that the desired boost in Th2 type immune responses to the antigen has been achieved.