Materials and methods for the delivery of therapeutic nucleic acids to tissues

Abstract

The present disclosure provides materials and methods for the delivery of therapeutic nucleic cells (and imaging agents) to tissues.

What is claimed is: 
     
         1 . A method of measuring beta cell mass comprising contacting the beta cell with a construct comprising an aptamer conjugated to an imaging reagent in an amount effective to measure the mass of the beta cell. 
     
     
         2 . The method of  claim 1 , wherein the aptamer is M12-3773 or 1-717. 
     
     
         3 . The method of  claim 1 , wherein the imaging agent is a fluorochrome, a PET tracer or a MRI contrast reagent. 
     
     
         4 . The method of  claim 1 , wherein the aptamer is conjugated to the imaging reagent via chelators. 
     
     
         5 - 16 . (canceled) 
     
     
         17 . An aptamer comprising the nucleotide sequence set forth in SEQ ID NO: 264 or SEQ ID NO: 259. 
     
     
         18 . (canceled) 
     
     
         19 . A construct comprising the aptamer of  claim 17  conjugated to a saRNA. 
     
     
         20 . The construct of  claim 19 , wherein the saRNA upregulates the protein XIAP (X-linked inhibitor of apoptosis gene id 331) or the protein CD274 (Programmed death-ligand 1, PDL1, gene id 29126).. 
     
     
         21 . (canceled) 
     
     
         22 . A construct comprising an aptamer conjugated to a small activating RNA (saRNA). 
     
     
         23 . The construct of  claim 22 , wherein the aptamer is specific for a tissue. 
     
     
         24 . The construct of  claim 23 , wherein the tissue is from an organ. 
     
     
         25 . The construct of  claim 24 , wherein the organ is pancreas, heart, lung, kidney, stomach, skin or brain. 
     
     
         26 . The construct of  claim 23 , wherein the tissue is pancreatic islets. 
     
     
         27 . The construct of  claim 22 , wherein the construct further comprises a detectable label. 
     
     
         28 . The construct of  claim 27 , wherein the detectable label is a fluorochrome, Positron emission tomography tracer such as Fluorine-18, oxygen-15, gallium 68, magnetic resonance imaging contrast agents such as gadolinium, iron oxide, iron platinum or manganese. 
     
     
         29 . The construct of  claim 22 , wherein the aptamer is M12-3773 or 1-717. 
     
     
         30 . The construct of  claim 22 , wherein the aptamer is specific for clusterin (CLU, gene id 1191). 
     
     
         31 . The construct of  claim 22 , wherein the aptamer is specific for “Transmembrane emp24 domain-containing protein 6” (TMED6, gene id 146456). 
     
     
         32 . The construct of  claim 22 , wherein the tissue is adrenal tissue,bone marrow, breast tissue, lung tissue or lymph node tissue, brain cerebellum, is brain cerebral cortex tissue, pituitary tissue, colon tissue, endothelium tissue, esophaqus tissue, heart tissue, kidney tissue, fallopian tube tissue, liver tissue, ovarian tissue, placenta tissue, prostate tissue, spinal cord tissue, testis tissue, thymus tissue, thyroid tissue, ureter tissue, cervical tissue, islets of Langerhans or pancreatic tissue. 
     
     
         33 . The construct of  claim 32 , wherein the aptamer is
 (a) 173-2273, 107-901 or m6-3239;   (b) 107-901 or m6-3239;   (c) 173-2273, 107-901, m1-2623 or m6-3239;   (d) 107-901, m1-2623 or m6-3239;   (e) m6-3239;   (f) 166-279, 107-901, m1-2623 or m6-3239;   (g) 107-901;   (h) 166-270, 173-2273, 107-901, m1-2623 or m6-3239;   (i) 173-2273 or 107-901;   (j) 166-279 or 173-2273;   (k) 166-279, 173-2273, 107-901, m1-2623, m6-3239 and m12-3773;   (l) 173-2273, 107-901 or mf-2623;   (m) m1-2623;   (n) 166-279; or   (o) 166-279, 173-2273, 107-901, 1-717, m1-2623, m6-3239 or m12-3773 .   
     
     
         34 - 64 . (canceled)