Anti-fibrotic compositions comprising fendrr or fragments or variants thereof and methods of production and use thereof

Abstract

Compositions containing long non-coding RNAs (IncRNA's) or fragments or variants thereof are disclosed. Also disclosed are compositions containing vectors that include or encode the IncRNA's or fragments/variants thereof. Further disclosed are methods of producing and using these compositions containing or encoding the IncRNA's.

What is claimed is: 
     
         1 . An anti-fibrotic composition, comprising:
 an isolated and/or purified Fetal-lethal noncoding developmental regulatory RNA (FENDRR) IncRNA or a fragment or variant thereof; and   a pharmaceutically-acceptable carrier.   
     
     
         2 . The anti-fibrotic composition of  claim 1 , wherein the FENDRR IncRNA or fragment or variant thereof is encoded by a sequence comprising at least about 100 contiguous nucleotides of at least one of SEQ ID NOS:1-3 and 133-134, or a sequence that differs from at least one of SEQ ID NOS:1-3 and 133-134 by less than about 30 amino acids. 
     
     
         3 . The anti-fibrotic composition of  claim 1 , wherein the FENDRR IncRNA or fragment or variant thereof is encapsulated. 
     
     
         4 . The anti-fibrotic composition of  claim 3 , further comprising a delivery vehicle in which the FENDRR IncRNA or fragment or variant thereof is encapsulated, wherein the delivery vehicle is selected from the group consisting of a liposome, a lipoplex, a microvesicle, an exosome, a lipidoid nanoparticle, a polymeric nanoparticle, an inorganic nanoparticle, and a stable nucleic acid particle (SNALP). 
     
     
         5 . A pharmaceutical composition, comprising:
 a vector comprising a sequence encoding at least about 100 contiguous nucleotides of a Fetal-lethal noncoding developmental regulatory RNA (FENDRR) IncRNA or a fragment or variant thereof; and   a pharmaceutically-acceptable carrier.   
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein the sequence comprises at least about 100 contiguous nucleotides of at least one of SEQ ID NOS:1-3 and 133-134, or a sequence that differs from at least one of SEQ ID NOS:1-3 and 133-134 by less than about 30 amino acids. 
     
     
         7 . The pharmaceutical composition of  claim 5 , wherein the vector is an adenoviral vector, an adeno-associated viral (AAV) vector, an alpha viral vector, a herpes viral vector, a lentiviral vector, a measles viral vector, a pox viral vector, a phage vector, or a retroviral vector. 
     
     
         8 . The pharmaceutical composition of  claim 5 , wherein the vector further comprises an expression control sequence to which the sequence is operably linked. 
     
     
         9 . A method of inhibiting activation of lung fibroblasts, the method comprising the step of:
 contacting the lung fibroblasts with a composition selected from the group consisting of:
 (i) an isolated and/or purified Fetal-lethal noncoding developmental regulatory RNA (FENDRR) IncRNA or a fragment or variant thereof; or 
 (ii) a vector comprising a sequence encoding at least about 100 contiguous nucleotides of a Fetal-lethal noncoding developmental regulatory RNA (FENDRR) IncRNA or a fragment or variant thereof. 
   
     
     
         10 . The method of  claim 9 , wherein in (i), the FENDRR IncRNA or fragment or variant thereof is encoded by a sequence comprising at least about 100 contiguous nucleotides of at least one of SEQ ID NOS:1-3 and 133-134, or a sequence that differs from at least one of SEQ ID NOS:1-3 and 133-134 by less than about 30 amino acids, and wherein in (ii), the sequence comprises at least about 100 contiguous nucleotides of at least one of SEQ ID NOS:1-3 and 133-134, or a sequence that differs from at least one of SEQ ID NOS:1-3 and 133-134 by less than about 30 amino acids. 
     
     
         11 . The method of  claim 9 , wherein in (i), the FENDRR IncRNA or fragment or variant thereof is encapsulated in a delivery vehicle, wherein the delivery vehicle is selected from the group consisting of a liposome, lipid nanoparticles, a lipoplex, a microvesicle, an exosome, a lipidoid nanoparticle, a polymeric nanoparticle, an inorganic nanoparticle, and a stable nucleic acid particle (SNALP). 
     
     
         12 . The method of  claim 9 , wherein in (ii), the vector is an adenoviral vector, an adeno-associated viral (AAV) vector, an alpha viral vector, a herpes viral vector, a lentiviral vector, a measles viral vector, a pox viral vector, a phage vector, or a retroviral vector. 
     
     
         13 . The method of  claim 9 , wherein in (ii), the vector further comprises an expression control sequence to which the sequence is operably linked. 
     
     
         14 . A method of treating or reducing the occurrence of pulmonary fibrosis in a subject, comprising the step of:
 administering a composition to the subject, wherein the composition is selected from the group consisting of:
 (i) a composition comprising a Fetal-lethal noncoding developmental regulatory RNA (FENDRR) IncRNA or a fragment or variant thereof and a pharmaceutically-acceptable carrier; or 
 (ii) a composition comprising a vector and a pharmaceutically-acceptable carrier, wherein the vector comprises a sequence encoding at least about 100 contiguous nucleotides of a Fetal-lethal noncoding developmental regulatory RNA (FENDRR) IncRNA or a fragment or variant thereof. 
   
     
     
         15 . The method of  claim 14 , wherein the composition is administered via a route selected from the group consisting of oral, topical, transdermal, parenteral, subcutaneous, intranasal, intratracheal, intrabronchial, mucosal, intramuscular, intraperitoneal, intravitreal, and intravenous routes. 
     
     
         16 . The method of  claim 14 , wherein in (i), the FENDRR IncRNA or fragment or variant thereof is encoded by a sequence comprising at least about 100 contiguous nucleotides of at least one of SEQ ID NOS:1-3 and 133-134, or a sequence that differs from at least one of SEQ ID NOS:1-3 and 133-134 by less than about 30 amino acids, and wherein in (ii), the sequence comprises at least about 100 contiguous nucleotides of at least one of SEQ ID NOS:1-3 and 133-134, or a sequence that differs from at least one of SEQ ID NOS:1-3 and 133-134 by less than about 30 amino acids. 
     
     
         17 . The method of  claim 14 , wherein in (i), the FENDRR IncRNA or fragment or variant thereof is encapsulated in a delivery vehicle, wherein the delivery vehicle is selected from the group consisting of a liposome, a lipoplex, a microvesicle, an exosome, a lipidoid nanoparticle, a polymeric nanoparticle, an inorganic nanoparticle, and a stable nucleic acid particle (SNALP). 
     
     
         18 . The method of  claim 14 , wherein in (ii), the vector is an adenoviral vector, an adeno-associated viral (AAV) vector, an alpha viral vector, a herpes viral vector, a lentiviral vector, a measles viral vector, a pox viral vector, a phage vector, or a retroviral vector. 
     
     
         19 . The method of  claim 14 , wherein in (ii), the vector further comprises an expression control sequence to which the sequence is operably linked. 
     
     
         20 . The method of  claim 14 , further defined as a method of treating or reducing the occurrence of idiopathic pulmonary fibrosis in a subject.