Modulation of transthyretin expression

Abstract

Compounds, compositions and methods are provided for modulating the expression of transthyretin. The compositions comprise oligonucleotides, targeted to nucleic acid encoding transthyretin. Methods of using these compounds for modulation of transthyretin expression and for diagnosis and treatment of diseases and conditions associated with expression of transthyretin are provided.

1 .- 18 . (canceled) 
     
     
         19 . A formulation comprising a liposome and a modulator of transthyretin expression. 
     
     
         20 . The formulation of  claim 19 , wherein the modulator of transthyretin expression is an antisense compound, an antisense oligonucleotide, or a ribozyme capable of hybridizing to at least a portion of SEQ ID NO: 4. 
     
     
         21 . The formulation of  claim 20 , wherein the antisense compound is single-stranded. 
     
     
         22 . The formulation of  claim 20 , wherein the antisense compound comprises a modified oligonucleotide 20 to 25 nucleobases in length having at least one modified sugar moiety. 
     
     
         23 . The formulation of  claim 22 , wherein the modified oligonucleotide is at least 95% complementary to SEQ ID NO: 4. 
     
     
         24 . The formulation of  claim 19 , wherein the liposome comprises a neutral lipid. 
     
     
         25 . The formulation of  claim 24 , wherein the neutral lipid comprises dioleoylphosphatidyl ethanolamine, dimyristoylphosphatidyl choline, or distearolyphosphatidyl choline. 
     
     
         26 . The formulation of  claim 19 , wherein the liposome comprises a negative lipid. 
     
     
         27 . The formulation of  claim 26 , wherein the negative lipid comprises dimyristoylphosphatidyl glycerol. 
     
     
         28 . The formulation of  claim 19 , wherein the modulator is encapsulated within the liposome. 
     
     
         29 . The formulation of  claim 20 , wherein the modulator is encapsulated within the liposome. 
     
     
         30 . The formulation of  claim 21 , wherein the modulator is encapsulated within the liposome. 
     
     
         31 . The formulation of  claim 22 , wherein the modulator is encapsulated within the liposome. 
     
     
         32 . The formulation of  claim 23 , wherein the modulator is encapsulated within the liposome. 
     
     
         33 . The formulation of  claim 24 , wherein the modulator is encapsulated within the liposome. 
     
     
         34 . The formulation of  claim 26 , wherein the modulator is encapsulated within the liposome.