Spherical nucleic acid-based constructs as immunostimulatory agents for prophylactic and therapeutic use

Abstract

Aspects of the invention relate to spherical nucleic acid-based constructs and related methods and compositions thereof. The compositions of the invention are useful for activating agonists of nucleic acid interacting complexes, such as TLRs, stimulating an immune response, and treating diseases such as infectious disease, cancer, allergies, allergic diseases, and autoimmune disease

What is claimed is: 
     
         1 . A nanoscale construct comprising:
 a corona comprised of an exterior shell composed of nucleic acid molecules arranged in a geometrical position and forming a spherical shape around a nanoparticle core, wherein the nucleic acid molecules are CpG oligonucleotides, wherein the nanoscale construct is about 1 nm to about 40 nm in diameter, and wherein the nanoparticle core at the center of the corona is not metallic.   
     
     
         2 . The nanoscale construct of  claim 1 , wherein the surface density of the nucleic acid molecules is at least 0.3 pmol/cm 2 . 
     
     
         3 . The nanoscale construct of  claim 1 , wherein the nucleic acid molecules comprise a spacer. 
     
     
         4 . The nanoscale construct of  claim 3 , wherein the spacer consists of oligoethylene. 
     
     
         5 . The nanoscale construct of  claim 1 , wherein the nanoparticle core at the center of the corona is hollow. 
     
     
         6 . The nanoscale construct of  claim 1 , wherein the nanoscale construct is degradable. 
     
     
         7 . The nanoscale construct of  claim 1 , wherein the CpG oligonucleotide has a modified backbone. 
     
     
         8 . The nanoscale construct of  claim 1 , further comprising an antigen. 
     
     
         9 . A method for delivering a therapeutic agent to a cell comprising delivering the nanoscale construct of  claim 1  to the cell. 
     
     
         10 . A method of treating a subject, comprising administering to the subject a nanoscale construct in an effective amount to stimulate an immune response, wherein the nanoscale construct comprises a corona having an exterior shell composed of nucleic acid molecules arranged in a geometrical position and forming a spherical shape around a nanoparticle core, wherein the nucleic acid molecules are CpG oligonucleotides, and wherein the nanoscale construct is about 1 nm to about 40 nm in [[mean]] diameter, and wherein the nanoparticle core at the center of the corona is not metallic. 
     
     
         11 . The method of  claim 10 , wherein the subject has an infectious disease. 
     
     
         12 . The method of  claim 10 , wherein the subject has cancer. 
     
     
         13 . A method for activating a toll-like receptor (TLR), the method comprising delivering to a cell a nanoscale construct, wherein the nanoscale construct comprises a corona having an exterior shell composed of nucleic acid molecules arranged in a geometrical position and forming a spherical shape around a nanoparticle core, wherein the nucleic acid molecules are CpG oligonucleotides, wherein the nanoscale construct is about 1 nm to about 40 nm in diameter, and wherein the nanoparticle core at the center of the corona is not metallic. 
     
     
         14 . The method of  claim 13 , wherein the cell is in vivo. 
     
     
         15 . The method of  claim 14 , wherein the nanoscale construct is administered to a subject having cancer. 
     
     
         16 . The nanoscale construct of  claim 4 , wherein the oligoethylene is hexaethylene glycol. 
     
     
         17 . The nanoscale construct of  claim 4 , wherein the spacer consists of two or three hexaethylene glycols. 
     
     
         18 . The nanoscale construct of  claim 3 , wherein the spacer does not comprise an oligonucleotide. (New) The nanoscale construct of  claim 1 , wherein the CpG oligonucleotide has a phosphorothioate (PS) backbone. 
     
     
         20 . A nucleic acid molecule comprising a CpG oligonucleotide having the nucleotide sequence of SEQ ID NO: 30, wherein the nucleic acid molecule comprises a spacer consisting of oligoethylene. 
     
     
         21 . The nucleic acid molecule of  claim 20 , wherein the CpG oligonucleotide has a phosphorothioate (PS) backbone. 
     
     
         22 . The nucleic acid molecule of  claim 20 , wherein the oligoethylene is hexaethylene glycol. 
     
     
         23 . The nucleic acid molecule of  claim 20 , wherein the spacer consists of two or three hexaethylene glycols. 
     
     
         24 . A plurality of nanoscale constructs, each nanoscale construct comprising:
 a corona comprised of an exterior shell composed of nucleic acid molecules arranged in a geometrical position and forming a spherical shape around a nanoparticle core, wherein the nucleic acid molecules are CpG oligonucleotides, wherein the nanoscale constructs have a mean diameter of about 1 nm to about 40 nm, and wherein the nanoparticle core at the center of the corona is not metallic.