Treatment strategies against anthrax by interfering with critical host factors
The present invention includes a composition and method for decreasing Bacillus anthracis virulence or toxicity comprising: at least one inhibitor that decreases an expression of one or more host genes selected from G6pc, Rgs1, Fosl2, Hcar2, Cxcl2 and Cxcl3, or Serpine1 (PAI-1).
1. A composition for decreasing virulence or toxicity of Bacillus anthracis to a host comprising:
inhibitors that decrease an expression of host genes Fosl2, Hcar2, Cxcl2, and Cxcl3, wherein a decrease in the expression of the host genes reduces a cell surface expression of Hcar2, and expression of Fosl2, Cxcl2 and Cxcl3, and wherein the reduction in expression of Hcar2, and Fosl2, Cxcl2, and Cxcl3, decreases the virulence or toxicity of the Bacillus anthracis to the host cell, wherein the inhibitors comprise an RNA molecule active for gene silencing through RNA interference (RNAi) against Fosl2 selected from SEQ ID NOS: 32, 34, or 36; against Hcar2 selected from SEQ ID NOS: 26, 28, or 30; against Cxcl2 selected from SEQ ID NOS: 46 and 48; and against Cxcl3 selected from SEQ ID NOS: 50 and 52.
2. The composition of claim 1 , further comprising a pharmaceutically acceptable carrier.
3. The composition of claim 2 , wherein the carrier is a lipid molecule or liposome.
4. The composition of claim 1 , wherein the RNA molecule comprises a polynucleotide sense strand and a polynucleotide antisense strand that are connected as a single strand, and form a duplex region connected at one end by a loop.
5. The composition of claim 4 , wherein at least one polynucleotide in any strand is at least chemically modified at one base.
6. The composition of claim 1 , wherein the RNA molecule is selected from the group consisting of siRNA, shRNA, a bishRNA, and miRNA.
7. The composition of claim 1 , wherein the virulence is cardiotoxicity or hepatotoxicity.
8. The composition of claim 1 , wherein each of the inhibitors is a polynucleotide selected from SEQ ID NOS: 1-58.
9. A composition comprising of:
inhibitors that decreases an expression of host genes Fosl2, Hcar2, or Cxcl2 and Cxcl3, in an amount sufficient to decrease the virulence or toxicity of a Bacillus anthracis to a host, wherein the inhibitors are RNA molecules active for gene silencing through RNA interference (RNAi) against Fosl2 selected from SEQ ID NO: 32, 34 or 36; against Hcar2 selected from SEQ ID NO:26, 28, or 30; against Cxcl2 selected from SEQ ID NO: 46 and 48; and against Cxcl3 selected from SEQ ID NOS: 50 and 52.