Screening and therapeutic method for nsclc targeting cdca1-kntc2 complex

Abstract

The present invention is based on the observation that the co-activation of CDCA1 and KNTC2, and their cognate interactions, play significant roles in lung-cancer progression and that methods of inhibiting the complex can be used to treat non-small-cell lung cancer.

1 - 15 . (canceled) 
     
     
         16 . A double-stranded molecule comprising a sense strand and an antisense strand, wherein the sense strand comprises a ribonucleotide sequence corresponding to a KNTC2 target sequence, and the antisense strand comprises a ribonucleotide sequence which is complementary to said sense strand, further wherein said sense strand and said antisense strand hybridize to each other to form said double-stranded molecule, and said double-stranded molecule, when introduced into a cell expressing a KNTC2 gene, inhibits the expression of said gene. 
     
     
         17 . The double-stranded molecule of  claim 16 , wherein said KNTC2 target sequence comprises at least about 10 contiguous nucleotides from the nucleotide sequence of SEQ ID NO: 31. 
     
     
         18 . The double-stranded molecule of  claim 17 , wherein said KNTC2 target sequence comprises from about 19 to about 25 contiguous nucleotides from the nucleotide sequence of SEQ ID NO: 9. 
     
     
         19 . The double-stranded molecule of  claim 18 , wherein said KNTC2 target sequence consists of SEQ ID NO: 9. 
     
     
         20 . The double-stranded molecule of  claim 16 , wherein said double-stranded molecule is a single ribonucleotide transcript comprising the sense strand and the antisense strand linked via a single-stranded ribonucleotide sequence. 
     
     
         21 . The double-stranded molecule of  claim 16  wherein the double-stranded molecule is an oligonucleotide of less than about 100 nucleotides in length. 
     
     
         22 . The double-stranded molecule of  claim 21 , wherein the double-stranded molecule is an oligonucleotide of less than about 75 nucleotides in length. 
     
     
         23 . The double-stranded molecule of  claim 22 , wherein the double-stranded molecule is an oligonucleotide of less than about 50 nucleotides in length. 
     
     
         24 . The double-stranded molecule of  claim 23 , wherein the double-stranded molecule is an oligonucleotide of less than about 25 nucleotides in length. 
     
     
         25 . The double-stranded polynucleotide of  claim 24 , wherein the double stranded molecule is an oligonucleotide of between about 19 and about 25 nucleotides in length. 
     
     
         26 . A vector encoding the double-stranded molecule of  claim 16 . 
     
     
         27 . The vector of  claim 26 , wherein the vector encodes a transcript having a secondary structure that comprises the sense strand and the antisense strand. 
     
     
         28 . The vector of  claim 27 , wherein the transcript further comprises a single-stranded ribonucleotide sequence linking said sense strand and said antisense strand. 
     
     
         29 . A vector comprising a polynucleotide comprising a combination of a sense strand nucleic acid and an antisense strand nucleic acid, wherein said sense strand nucleic acid comprises a nucleotide sequence consisting of SEQ ID NO: 9, and said antisense strand nucleic acid consists of a sequence complementary to said sense strand. 
     
     
         30 . The vector of  claim 29 , wherein said polynucleotide has the general formula 5′-[A]-[B]-[A′]-3′, wherein [A] is a nucleotide sequence of SEQ ID NO: 9; [B] is a nucleotide sequence consisting of 3 to 23 nucleotides; and [A′] is a nucleotide sequence complementary to [A]. 
     
     
         31 . A composition for treating or preventing NSCLC, said composition comprising a pharmaceutically effective amount of an siRNA against a KNTC2 gene. 
     
     
         32 . The composition of  claim 31 , wherein the siRNA comprises a sense strand comprising the nucleotide sequence of SEQ ID NO: 9, as the target sequence. 
     
     
         33 .- 42 . (canceled)