Treating cancer with viral nucleic acid

Abstract

This document provides methods and materials related to the use of nucleic acid coding for viruses to reduce the number of viable cancer cells within a mammal. For example, methods for using infectious nucleic acid to treat cancer, engineered viral nucleic acid, methods for making engineered viral nucleic acid, methods for identifying infectious nucleic acid for treating cancer, methods and materials for controlling virus-mediated cell lysis, and methods and materials for assessing the control of virus-mediated cell lysis are provided.

1 . A method for treating cancer present in a mammal, wherein said method comprises administering, to said mammal, an effective amount of nucleic acid coding for a picornavirus under conditions wherein cancer cells present within said mammal undergo cell lysis as a result of synthesis of picornavirus from said nucleic acid, thereby reducing the number of viable cancer cells present within said mammal. 
     
     
         2 . The method of  claim 1 , wherein said mammal is a human. 
     
     
         3 . The method of  claim 1 , wherein said effective amount is between about 3×10 10  and about 3×10 14  virus genome copies. 
     
     
         4 . The method of  claim 1 , wherein said picornavirus is a coxsackievirus. 
     
     
         5 . The method of  claim 1 , wherein said cancer cells are myeloma, melanoma, or breast cancer cells. 
     
     
         6 . The method of  claim 1 , wherein said nucleic acid comprises a microRNA target element comprising at least a region of complementary to a microRNA present in non-cancer cells. 
     
     
         7 . The method of  claim 6 , wherein a reduced number of non-cancer cells present within said mammal undergo cell lysis as compared to the number of non-cancer cells that would undergo cell lysis when said nucleic acid lacks said microRNA target element. 
     
     
         8 . The method of  claim 6 , wherein said microRNA is a tissue-specific microRNA. 
     
     
         9 . The method of  claim 6 , wherein said microRNA is a muscle-specific, brain-specific, or heart-specific microRNA. 
     
     
         10 . An isolated nucleic acid coding for a virus and comprising a microRNA target element having at least a region that is complementary to at least a region of a microRNA present in non-cancer cells and that is heterologous to said virus. 
     
     
         11 . The isolated nucleic acid of  claim 10 , wherein said virus is a picornavirus. 
     
     
         12 . The isolated nucleic acid of  claim 10 , wherein said virus is a coxsackievirus. 
     
     
         13 . The isolated nucleic acid of  claim 10 , wherein said virus is a poliovirus. 
     
     
         14 . The isolated nucleic acid of  claim 10 , wherein said microRNA is a tissue-specific microRNA. 
     
     
         15 . The isolated nucleic acid of  claim 10 , wherein said microRNA is a muscle-specific, brain-specific, or heart-specific microRNA. 
     
     
         16 . An isolated nucleic acid coding for a virus and comprising a microRNA target element having at least a region that is complementary to at least a region of a cancer-specific microRNA and that is heterologous to said virus. 
     
     
         17 . The isolated nucleic acid of  claim 16 , wherein said nucleic acid, when administered to a mammal having cancer, is expressed in cancer cells. 
     
     
         18 . The isolated nucleic acid of  claim 16 , wherein expression of said nucleic acid is restricted to cancer cells containing said cancer-specific microRNA when said nucleic acid is administered to a mammal having cancer. 
     
     
         19 . A method of assessing coxsackievirus-mediated cell lysis of non-cancer cells, wherein said method comprises:
 (a) administering nucleic acid coding for a coxsackievirus to a mammal, and   (b) determining whether or not said mammal develops myositis, paralysis, or death, wherein the presence of said myositis, paralysis, or death indicates that said nucleic acid causes coxsackievirus-mediated cell lysis of non-cancer cells, and wherein the absence of said myositis, paralysis, and death indicates that said nucleic acid lacks significant coxsackievirus-mediated cell lysis of non-cancer cells.   
     
     
         20 . The method of  claim 19 , wherein said mammal is a mouse. 
     
     
         21 . The method of  claim 19 , wherein said nucleic acid comprises a microRNA target element that is complementary to a microRNA present in non-cancer cells and that is heterologous to said coxsackievirus. 
     
     
         22 . The method of  claim 21 , wherein said microRNA is a tissue-specific microRNA. 
     
     
         23 . The method of  claim 21 , wherein said microRNA is a muscle-specific microRNA.