Nucleic acid compounds for inhibiting angiogenesis and tumor growth

Abstract

In certain embodiments, this present disclosure provides nucleic acid compounds, compositions, and methods for inhibiting Ephrin B2 or EphB4 expression. In certain embodiments, the present disclosure provides methods and compositions for treating cancer or for treating angiogenesis-associated diseases.

1 . An isolated RNAi construct comprising at least a portion that hybridizes to an EphB4 transcript sequence set forth in SEQ ID NO: 392 under physiological conditions and decreases the expression of EphB4 in a cell. 
     
     
         2 - 6 . (canceled) 
     
     
         7 . The isolated RNAi construct of  claim 1 , wherein the RNAi construct is single-stranded. 
     
     
         8 . The isolated RNAi construct of  claim 1 , wherein the RNAi construct is double-stranded. 
     
     
         9 - 10 . (canceled) 
     
     
         11 . The isolated RNAi construct of  claim 1 , wherein the RNAi construct comprises a DNA strand and a RNA strand and optionally comprises one or more modified backbone or base moieties. 
     
     
         12 - 22 . (canceled) 
     
     
         23 . The isolated RNAi construct of  claim 1 , wherein the RNAi construct comprises one or more modified backbone or base moieties. 
     
     
         24 - 28 . (canceled) 
     
     
         29 . The isolated RNAi construct of  claim 1 , wherein the RNAi construct inhibits EphB4 expression in cells by 50% or greater, when contacted with the cells under physiological conditions at a concentration of 5 micromolar. 
     
     
         30 . An isolated RNAi construct comprising at least a portion that hybridizes to an EphrinB2 transcript sequence set forth in SEQ ID NO: 394 under physiological conditions and decreases the expression of EphrinB2 in a cell. 
     
     
         31 - 35 . (canceled) 
     
     
         36 . The nucleic acid compound of  claim 30 , wherein the nucleic acid compound is single-stranded. 
     
     
         37 . The nucleic acid compound of  claim 30 , wherein the nucleic acid compound is double-stranded. 
     
     
         38 - 40 . (canceled) 
     
     
         41 . The nucleic acid compound of  claim 30 , wherein the nucleic acid compound is an antisense nucleic acid compound. 
     
     
         42 - 43 . (canceled) 
     
     
         44 . The nucleic acid compound of  claim 41 , wherein the antisense nucleic acid compound comprises one or modified backbone or base moieties. 
     
     
         45 - 46 . (canceled) 
     
     
         47 . The nucleic acid compound of  claim 30 , wherein the nucleic acid compound is a RNAi construct. 
     
     
         48 - 51 . (canceled) 
     
     
         52 . The nucleic acid compound of  claim 47 , wherein the RNAi construct comprises one or more modified backbone or base moieties. 
     
     
         53 - 57 . (canceled) 
     
     
         58 . The nucleic acid compound of  claim 30 , wherein the nucleic acid compound inhibits EphrinB2 expression in cells by 50% or greater, when contacted with the cells under physiological conditions at a concentration of 5 micromolar. 
     
     
         59 . A pharmaceutical composition comprising a nucleic acid compound and a pharmaceutically acceptable carrier, wherein the nucleic acid compound is selected from:
 (a) an RNAi construct comprising at least a portion that hybridizes to an EphB4 transcript under physiological conditions and decreases the expression of EphB4 in a cell; and   (b) an RNAi construct comprising at least a portion that hybridizes to an EphrinB2 transcript under physiological conditions and decreases the expression of EphrinB2 in a cell.   
     
     
         60 . (canceled) 
     
     
         61 . A method of inhibiting EphB4 expression in a cell, comprising contacting the cell with an effective amount of the isolated RNAi construct of  claim 1 . 
     
     
         62 . (canceled) 
     
     
         63 . A method of inhibiting Ephrin B2 expression in a cell, comprising contacting the cell with an effective amount of the nucleic acid compound of  claim 30 . 
     
     
         64 . (canceled) 
     
     
         65 . A method of reducing the growth rate of a tumor in a subject, comprising administering an amount of a nucleic acid compound sufficient to reduce the growth rate of the tumor, wherein the nucleic acid compound is selected from:
 (a) an RNAi construct comprising at least a portion that hybridizes to an EphB4 transcript under physiological conditions and decreases the expression of EphB4 in a cell; and   (b) an RNAi construct comprising at least a portion that hybridizes to an EphrinB2 transcript under physiological conditions and decreases the expression of EphrinB2 in a cell.   
     
     
         66 . (canceled) 
     
     
         67 . A method for treating a patient suffering from a cancer, comprising administering to the patient a nucleic acid compound selected from:
 (a) an RNAi construct comprising at least a portion that hybridizes to an EphB4 transcript under physiological conditions and decreases the expression of EphB4 in a cell; and   (b) an RNAi construct comprising at least a portion that hybridizes to an EphrinB2 transcript under physiological conditions and decreases the expression of EphrinB2 in a cell.   
     
     
         68 - 77 . (canceled) 
     
     
         78 . A method for treating a patient suffering from an angiogenesis-associated disease, comprising administering to the patient an amount of a nucleic acid compound sufficient to inhibit angiogenesis, wherein the nucleic acid compound is selected from:
 (a) an RNAi construct comprising at least a portion that hybridizes to an EphB4 transcript under physiological conditions and decreases the expression of EphB4 in a cell; and   (b) an RNAi construct comprising at least a portion that hybridizes to an EphrinB2 transcript under physiological conditions and decreases the expression of EphrinB2 in a cell.   
     
     
         79 - 91 . (canceled)