Methods and compositions for the inhibition of hiv-1 replication

Abstract

This invention relates to methods and compositions for the attenuation of HIV-1 replication in human cells, and especially in human macrophages. The invention particularly concerns the use of inhibitors of P21 (CDKNIA) expression to attenuate such replication. The invention particularly concerns the use of antisense P21 oligonucleotides, siRNA and/or 2-cyano-3,12-dioxooleana-1,9-dien28-oic (CDDO) to attenuate such replication.

1 . A method of attenuating the transmission or infection of an immunodeficiency virus into a cell comprising providing to said cell an inhibitor of p21, wherein said inhibitor is a polynucleotide provided in an amount and duration sufficient to cause an attenuation of at least about 50% in said transmission or infection of said virus relative to an untreated cell. 
     
     
         2 . The method of  claim 1 , wherein said immunodeficiency virus is human immunodeficiency virus (HIV), and said cell is a human cell. 
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 2 , wherein said polynucleotide is complementary to a portion of a p21 gene or p21 cDNA molecule. 
     
     
         5 . The method of  claim 4 , wherein said p21 gene or p21 cDNA is of a human p21 gene or p21 cDNA molecule. 
     
     
         6 . The method of  claim 5 , wherein said polynucleotide comprises at least 10 contiguous nucleotides of SEQ ID NO.:4. 
     
     
         7 . The method of  claim 6 , wherein said polynucleotide comprises at least 10 contiguous nucleotides of SEQ ID NO.:8 or SEQ ID NO.:10. 
     
     
         8 . The method of  claim 4 , wherein said p21 gene or p21 cDNA is of a non-human animal or is a variant of a non-human p21 gene or p21 cDNA molecule. 
     
     
         9 . The method of  claim 8 , wherein said polynucleotide comprises at least 10 contiguous nucleotides of SEQ ID NO.:6. 
     
     
         10 . The method of  claim 9 , wherein said polynucleotide comprises at least 10 contiguous nucleotides of SEQ ID NO.:7 or SEQ ID NO.:9. 
     
     
         11 .- 12 . (canceled) 
     
     
         13 . A method of treating AIDS in an individual, comprising providing to HIV-1 infected cells of said individual, or to HIV 1 susceptible cells of such individual, an amount of a p21 inhibitor sufficient to attenuate the propagation of HIV, wherein said inhibitor is a polynucleotide provided in an amount and duration sufficient to cause an attenuation of at least 50% in said propagation of HIV relative to untreated cells. 
     
     
         14 . (canceled) 
     
     
         15 . The method of  claim 13 , wherein said polynucleotide is complementary to a portion of a p21 gene or p21 cDNA molecule. 
     
     
         16 . The method of  claim 15 , wherein said p21 gene or p21 cDNA is of a human p21 gene or p21 cDNA molecule. 
     
     
         17 . The method of  claim 16 , wherein said polynucleotide comprises at least 10 contiguous nucleotides of SEQ ID NO.:4. 
     
     
         18 . The method of  claim 17 , wherein said polynucleotide comprises at least 10 contiguous nucleotides of SEQ ID NO.:8 or SEQ ID NO.:10. 
     
     
         19 . The method of  claim 15 , wherein said p21 gene or p21 cDNA is of a non-human animal or is a variant of a non-human p21 gene or p21 cDNA molecule. 
     
     
         20 . The method of  claim 19 , wherein said polynucleotide comprises at least 10 contiguous nucleotides of SEQ ID NO.:6. 
     
     
         21 . The method of  claim 20 , wherein said polynucleotide comprises at least 10 contiguous nucleotides of SEQ ID NO.:7 or SEQ ID NO.:9. 
     
     
         22 .- 34 . (canceled)